A preliminary study of a new
painless and effective botulinum toxin

A jet nebulizer delivery for treatment of primary hyperhidrosis

Background: Hyperhidrosis is a chronic disease characterized by increased sweat production. Local injections of botulinum toxin A (BTX-A) have been extensively used for treatment of primary hyperhidrosis. The current treatment for this condition involves several intradermal injections, resulting in poor patient compliance due to injection-related pain. Therefore, new protocols, including an improved anesthetic regimen, are required.
Aim: We designed the present study to determine whether JetPeel™-3 could be used to deliver lidocaine prior to the standard BTX-A multiple injections or deliver lidocaine together with BTX-A in order to determine the protocol giving better results in terms of pain, sweating, and patient satisfaction in subjects affected by primary axillary, palmar, or plantar hyperhidrosis.
Materials and methods: Twenty patients with a visual analog scale (VAS) sweating ≥ 8 cm were randomized to receive lidocaine sprayed with JetPeel™-3 followed by multiple injections of BTX-A or lidocaine and BTX-A sprayed together with JetPeel™-3. Efficacy of treatment was measured by VAS for pain and sweating at 3-month follow-up. Patient satisfaction was assessed using a 5-point scale.
Results: Both BTX-A delivery modalities significantly reduced visual analog scale sweating, if compared with baseline (all P<0.001). Delivery of lidocaine and BTX-A by JetPeel™-3 significantly reduced VAS pain and sweating, if compared with lidocaine delivered by JetPeel™-3 followed by BTX-A multiple injections (all P<0.001). Patient satisfaction with the procedure was higher in the group receiving lidocaine and BTX-A treatment by JetPeel™-3, if compared with JetPeel™-3 used only for lidocaine delivery plus BTX-A multiple injections (P<0.001). No side effects were observed.
Conclusion: JetPeel™-3 can be used safely to treat palmar, plantar, and axillary hyperhidrosis, significantly reducing pain and sweating and improving patient satisfaction, if compared with standard therapy. The protocol based on JetPeel™-3 also requires a reduced quantity of BTX-A, if compared with standard therapy.
Keywords: hyperhidrosis, JetPeel™-3, botulinum toxin A, anesthesia, pain, sweating

Introduction

Hyperhidrosis

Hyperhidrosis is an eccrine sweat gland disorder resulting in an increase in sweating which goes beyond what is physiologically appropriate for temperature regulation, and can affect hands, palms, feet soles, axillae, face, and head. Primary hyperhidrosis is generally idiopathic and may be exacerbated under conditions of stress. It equally affects men and women (∼3% of the population) and its burden is mainly due to the significant social stigma and reduced quality of life.

Management of hyperhidrosis

The management of hyperhidrosis includes the use of topical antiperspirants such as aluminum chloride or tannic acids, oral anticholinergic medications such as glycopyrrolate and propantheline or iontophoresis.6 Local injections of botulinum toxin A (BTX-A) are effective in treating primary hyperhidrosis, because BTX-A blocks the release of acetylcholine from the presynaptic nerve terminal with a temporary and reversible local chemodenervation. However, as a great number of painful intradermal injections are required, many patients complain of pain during injections, causing poor compliance in the regular re-injection follow-up. Unfortunately, commonly used pain relief methods such as topical anesthesia, cooling of the skin and use of needles of reduced size have proven unsuccessful, requiring the design of new protocols.
A previous study in our laboratories showed that JetPeel™-3 (TavTech Ltd., Yehud, Israel) can be used successfully to deliver lidocaine with an anesthetic power superior to topical anesthetic cream in the aesthetic medicine setting. In the present study, we tested the hypothesis that JetPeel™-3 can be used to deliver lidocaine prior to standard BTX-A multiple injections or to deliver lidocaine plus BTX-A, in order to determine the protocol giving better results in terms of pain, sweating, and patient satisfaction.

Materials and methods

This study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board at the Poliambulatorio del Secondo Parere (Modena, Italy), where the study was performed.

Patients

Twenty patients, 13 women and 7 men, aged 39±2.63 years (mean ± standard error of the mean), were enrolled in this study. All patients signed the informed consent. Only patients affected by primary axillary, palmar, or plantar hyperhidrosis with a visual analog scale (VAS) sweating ≥ 8 cm. Exclusion criteria were neuromuscular disease, concomitant drug treatment interfering with neuroglandular transmission, infections, dermatitis or other skin diseases, allergy or sensitivity to the study medication, previous treatment with BTX-A in the 12 months preceding the study, pregnancy and breastfeeding.

JetPeel™-3

JetPeel™-3 is a medical device that can be used for dermoabrasion, dark spot removal, fine wrinkle smoothing, skin cleansing, squeezing of enlarged pores, dermoepidermal hydration and oxygenation, improvement in microcirculation rheology, dermal lymph drainage and transdermal drug delivery. Moreover, it can be used to achieve effective skin disinfection and/or surface sterilization and induce local anesthesia, avoiding the use of needles.21 A mixture of saline and oxygen is forced into a channel, which accelerates the droplets (200 m/sec) outside through a specific nozzle, delivering a powerful jet of microdroplets containing water, drug, air and oxygen (diameter 5–200 μm) onto the skin surface.

Experimental procedure

Patients were randomized to receive a single session of 1) lidocaine 2% (Astra Formedic, Milan, Italy; 5 mL) delivered by JetPeel™-3 and subsequent multiple BTX-A (100 U/vial; Bocouture®, Merz Aesthetics, Frankfurt am Main, Germany; BTX-A was reconstituted in 5 mL of saline solution) injections in the area affected by hyperhidrosis (group A [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][n=10]) or 2) lidocaine 2% (5 mL) and BTX-A injections (50 U/vial diluted into 5 mL of lidocaine for each palm, axilla, or foot) administered together with JetPeel™-3 (Figure 1) over the area affected by hyperhidrosis (group B [n=10]). In patients affected by axillary hyperhidrosis, the area was shaved 2 days before the procedure. Patients were instructed not to use antiperspirants or deodorants for at least 24 hours prior to treatment. Patient follow-up was performed at 3 months.

Treatment of palmar
Figure 1 Treatment of palmar (A), axillary (B), and plantar (C) hyperhidrosis with botulinum toxin A delivered by JetPeelTM-3.
Note: JetPeel™-3 is manufactured by TavTech Ltd., Yehud, Israel.

Measurement of pain, sweating, and patient satisfaction

Pain was rated using a visual analog scale (VAS) (0= minimum pain; 10= maximum pain). The patients were asked to quantify the intensity of sweating on a VAS (0= minimum sweating; 10= maximum sweating) before and after treatment. Patients’ satisfaction with the procedure was rated on a 5-point scale (1= none; 2= poor; 3= moderate; 4= good; 5= very good).

Statistical analysis

Data were analyzed using GraphPad Prism 6 software (GraphPad Software, Inc., La Jolla, CA, USA). Data were checked for normality using the D’Agostino and Pearson normality test. A two-sample unpaired Student’s t-test was applied to analyze differences in VAS pain and patient satisfaction between the two treatment groups. Differences in VAS sweating between the two drug delivery modalities were analyzed using two-way analysis of variance followed by Sidak’s multiple comparisons test.

Figure 2
Figure 2 (A) JetPeel™-3 (lidocaine + botulinum toxin A [BTX-A]) significantly decreases visual analog scale (VAS ) pain versus JetPeel™-3 (lidocaine) + multiple BTX-A injections; (B) JetPeel™-3 (lidocaine + BTX-A) significantly decreases VAS sweating versus JetPeel™-3 (lidocaine) + multiple BTX-A injections; (C) patients are significantly more satisfied with the JetPeel™-3 (lidocaine + BTX-A) protocol, if compared with JetPeel™-3 (lidocaine) + multiple BTX-A injection procedure.a
Notes: aData are presented as the mean ± standard error of the mean. ***P

Results

Patients from group A had axillary hyperhidrosis (n=3), plantar hyperhidrosis (n=3) or palmar hyperhidrosis (n=4). Patients belonging to group B had axillary hyperhidrosis (n=2), plantar hyperhidrosis (n=4), or palmar hyperhidrosis (n=4). Both BTX-A delivery modalities significantly reduced VAS sweating, if compared with baseline (all P<0.001). VAS sweating decreased from a baseline value of 8.7±0.3 cm to 4±0.2 cm in the group receiving lidocaine by JetPeel™-3 and multiple BTX-A injections. VAS sweating decreased from a baseline value of 8.9±0.2 cm to 2.2±0.3 cm in the group receiving lidocaine and BTX-A by JetPeel™-3. Delivery of lidocaine and BTX-A by JetPeel™-3 significantly reduced VAS pain and sweating, if compared with lidocaine delivered by JetPeel™-3 followed by BTX-A multiple injections (all P<0.001; Figure 2A and B). Patient satisfaction with the procedure was higher in the group receiving lidocaine and BTX-A treatment by JetPeel™-3, if compared with JetPeel™-3 used only for lidocaine delivery plus BTX-A multiple injections (P<0.001; Figure 2C). Cold-related pain was observed during axillary treatment in a patient after BTX-A injections. However, the patient completed the procedure successfully and the pain resolved within 20 minutes. No side effects were observed.

Discussion

Hyperhidrosis is overproduction of sweat by the exocrine sweat glands and is characterized by enormous psychosocial stress. We found that delivering BTX-A and lidocaine together with JetPeel™-3 resulted in a significant reduction in VAS pain and sweating at 3-month follow-up, if compared with lidocaine delivered by JetPeel™-3 and BTX-A multiple injections into the dermis. The greater benefit was observed when delivering the anesthetic together with BTX-A using JetPeel™-3, delivering a reduced quantity of BTX-A, further supporting the use of the jet nebulizer drug delivery versus standard injections. This evidence suggests a more direct penetration of the drug when using JetPeel™-3. Many studies have investigated the persistence of BTX-A injection for treatment of hyperhidrosis. For example, Naver et al reported a median duration of 10 months after injecting a mean dose of 60 mU BTX-A in 55 patients affected by axillary hyperhidrosis and a dose of 170 mU in 94 patients affected by palmar hyperhidrosis. Furthermore, Schnider et al14 injected 200 U of BTX-A in 13 subjects affected by axillary hyperhidrosis and found that the difference in VAS between the BTX-A-treated and placebo-treated axillae was −56.5% after 3 weeks, −67.4% after 8 weeks, and −62.5% after 13 weeks. In a further study, an injection of 100 U of BTX-A per palm in 36 patients affected by palmar and plantar hyperhidrosis resulted in a significant improvement at 6-month follow-up. In a further clinical study, Xeomin® (Merz Pharmaceuticals, Frankfurt, Germany), a type of BTX-A, was injected into patients affected by axillary hyperhidrosis, while patients affected by palmar hyperhidrosis, were injected with Xeomin® and Neurobloc® (Eisai Europe Ltd, Hatfield, UK), a type of BTX-B. At the 3-week follow-up, all patients, treated for axillary and palmar hyperhidrosis, reported a significant improvement in dermatology Life Quality Index (DLQI) score. Andrade et al found two efficient non-invasive methods, iontophoresis and phonophoresis, to administer BTX-A in patients with bilateral primary palmar hyperhidrosis. BTX-A efficacy lasted over 16 weeks after the end of treatment. In our previous study, JetPeel™-3 was used to successfully deliver carbocaine, resulting in significantly increased anesthesia in patients undergoing hyaluronic acid-based facial rejuvenation procedures, if compared with topical anesthetic cream.

 

Conclusion

The present study shows that JetPeel™-3 can be efficiently and safely used to treat palmar, plantar and axillary hyperhidrosis, delivering both anesthetic and BTX-A at the same time. Our protocol results in a significant reduction in pain and sweating and an increase in patient satisfaction, if compared with standard therapy, also requiring a reduced quantity of BTX-A used. A limitation of our study is the small number of patients involved in our preliminary investigation.

Acknowledgments

The authors contributed equally to this work. The authors hereby certify that all work contained in this article is original. The authors claim full responsibility for the content of the article. Written informed consent was obtained from the patients for publication of the data included in this manuscript.

Disclosure

The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

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The Use of a Jet-PhoresisTransdermal Delivery System for Pain Control – ASLMS 2010

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Summary Background and Objective:

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What is JetPeel?

  • A treatment based on supersonic delivery of materials, including actives, to the skin
  • Ability to simultaneously introduce active nutrients and oxygen into the skin, using pressure and air

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Current Study Design:

  • Prospective clinical study to compare lidocaine jet-phoresis trans-cutaneous anesthesia to EMLA 5% topical cream
  • 20 patients that were scheduled to undergo needling roller for upper lip rhytids enrolled into study
  • Each patient served as own control – 40 lips evaluated
  • Half of the upper lip had EMLA 5% cream applied for 45 minutes
  • Contra-lateral portion of the lip treated with lidocaine 3% jetphoresis for 5 minutes
  • Pain elicited with needling roller uniformly applied across the upper lip
  • Pain response measured using VAS scale

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Current Study Results:

  • Statistically significant advantage of pain control in the lidocaine jet-phoresis group compared to EMLA group
  • Jet-phoresis lidocaine pain control was better or comparable to EMLA in > 82% of lips
  • Further confirmed by reversing the sides of the tested lips in the same subjects

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Background: Basic Principles

 

  • Pressurized gas is used to accelerate a liquid agent (saline).
  • Water droplets accelerated to supersonic velocities (200 m/s)
  • The mixture of liquid and gas is emitted through a special nozzle unit.
  • The high velocity jet exfoliates the superficial layers of the skin

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Supersonic Technology:

  • Supersonic two-phase jet directed onto the skin with specialized handpieces and nozzles.
  • Spray consists of micro droplets of saline or supplements (actives) and gas (air, oxygen or CO2).
  • High velocity spray induces skin rejuvenation through exfoliation and supplementation.

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Results:

  • Statistically significant advantage of pain control in the mlidocaine jet-phoresis group compared to EMLA group
  • Jet-phoresis lidocaine pain control was better or comparable to EMLA in > 82% of lips
  • Further confirmed by reversing the sides of the tested lips in the same subjects

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The Jet Peel – 3 In Cosmetic Medicine And Surgery:

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B. Palmieri1, V. Rottigni1, A. Aspiro

University of Modena, Modena, Italy[/fusion_text][/fusion_builder_column][fusion_builder_column type=”2_3″ last=”no” spacing=”no” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”solid” padding=”” margin_top=”” margin_bottom=”” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ class=”” id=””][fusion_text]BACKGROUND

The history of needle–less injection by pressure guns is historically introduced in the clinical practice for local anesthesia. The drawback of this guns generation is a real tissue contusion and ecchimosis due to high pressure delivery.
A different approach to transepidermal delivery is an high pressure (7 atm), high speed (200 m/sec) air flow device called JetPeel, a medical instrument with different claims such as surfaceal smooth dermoabrasion, blackspots skin clearing, fine wrinkles smoothing, skin cleaning and dilated pores squeezing.

In our experience it achieves good effects either in skin disinfection, local anesthesia and molecules delivery.

In our study, we enrolled 20 subjects affected by hyperhidrosis for a treatment with botulinum. 10 patients received botulinum directly sprayed with JetPeel, while 10 patients were treated with botulinum injections after anesthesia sprayed with the device.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_3″ last=”yes” spacing=”no” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”solid” padding=”0 0 0 20px” margin_top=”” margin_bottom=”” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]

JetPeel TM – 3

(Tav Tech Inc., Yehud, Israel)

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Anesthesia (Lidocaine) with JetPeelTM – 3
followed by botulinum injection

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Botulinum delivery
with JetPeelTM – 3

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In both groups, the procedure was painless, since JetPeel is a not invasive device, and efficient for the treatment of excessive sweat conditions.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]CONCLUSIONS

  • No adverse effects (oedema, subcutaneous emphysema, bruising)
  • high efficacy for hyperhidrosis treatment
  • high patient satisfaction
  • no pain during both procedures

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The JetPeel – A Novel Delivery
System for Delivery into the Skin

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Michael H. Gold, M.D.

The JetPeel - A Novel Delivery System

Aims: The aim of this presentation is to introduce a novel, supersonic delivery system for the delivery of actives into the skin.

Methods: This presentation is a collection of the clinical work to date for this novel delivery system, showing how the device works to the various actives which are utilizes to improve the skin.

Today, skin rejuvenation procedures are among the most popular treatments for those in search of a youthful appearance. Sun and age-related imperfections such as wrinkles and pigmented lesions as well as scars and acne are all treated with a revolutionary, multifunctional, skin rejuvenation technology based on jet aviation engineering. A two phase supersonic jet that consists of microdroplets of saline solution and air is used to improve skin appearance in a non-invasive, short, painless treatment. The aesthetic market continues to expand, apparently with no end in sight. Over the last few years, skin rejuvenation procedures have become doctors’ favorite physician performed treatments, meeting patients’ needs in the rapidly expanding aesthetic, skin care market.

The new revolutionary technology used by the JetPeel system is recommended for a variety of skin conditions and enhances skin appearance in a non-invasive procedure. The system uses a specially designed handpiece to create a liquid-gas jet which is accelerated to 200m/sec. When the very small fast-moving droplets from the jet stream strike the skin several things happen:

ï The kinetic energy of the droplets exfoliates the outer layer of the epidermis. ï The pressure created by the high-velocity jet stretches the skin at the point of contact, causing micro-canals in the epidermis to broaden as the skin stretches and creating new canals. This process, called “barophoresis”, is the result of pressure variance. It facilitates hydration and cleansing of the treated area and without needles opens access to the skinís inner layers providing deeper penetration and allowing introduction of actives such as meso-therapy vitamins and other solutions. Nutritional elements currently being used include Hyaluronic acid which can reaches the ski’s natural connective tissue; vitamin C, which improves the ability of skin cells to even out pigments; and vitamin a, B and E which are important ingredients for the proper functioning of cells.

Due to its multi-purpose nature and painless treatment the JetPeel system is recommended for:[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]

  • Skin rejuvenation
  • Wrinkles: crowís feet, peri-oral etc.
  • Scars
  • Acne
  • Stretch marks
  • Enhancing results of laser, IPL and other treatments.

New medical-aesthetic techniques are designed to achieve several effects with a single treatment of short duration, with no downtime for the patient. The new JetPeelô3 answers this need as part of an anti-aging skincare program. The 200 meter per second micro-flow not only smoothes the skin, but also improves the various skin conditions that affect the patient’s appearance in a short non-invasive procedure. JetPeel can be used on any skin surface of the body and face, the pilous part of the head, dÈcolletÈ and on the hands and feet.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”center” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][/fusion_builder_column][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_text]Combining traditional procedures with JetPeel treatment is most beneficial in facial rejuvenation.

The JetPeel can be used for the trans-dermal delivery of nutrient supplements, mesotherapy products, vitamins and minerals without needles. A typical session lasts about 30-45 minutes for treatment of the full face. Patients feel comfortable and relaxed during the treatment and they appreciate the results. After a single session, the skin texture is improved; the skin looks more radiant and has a more youthful appearance.

The JetPeel advanced, painless technology can deliver actives transcutaneously without needles.

Experimental study was conducted by HPBM*. Its report is being presented hereby:

1. Executive Summary

Objectives: To test Caffeine transport parameters across skin sample following their treatments with Caffeine.

Main Findings: JetPeel Caffeine treatment resulted in an almost instant permeation of the compound. Caffeine high concentration levels were maintained for 20 hours.

2. Materials

Caffeine – Merek, Cat. No. 1.59692.0001

3. Methods

Caffeine Trasport

Skin Treatment

Caffeine was dissolved to 1mg/ml in water and used for JetPeel device treatment instead of water, for the duration of 1 minute. Treated and non-treated skin circles were cut along circle lines and placed in diffusion chambers.

Trasport System

5 cells of Diffusion Chamber System (Harvard) were filled with 3ml PBS at the basolateral side, and adjust to 35°C on heat block for 15-30 minutes.

At transport onset, apical side was loaded with 1mg/ml Caffeine in water

Aliquots were removed at 0.5, 2, 6 and 20 hours fresh PBS replaced the exact removed volume.

HPLC Analysis

Aliquoted samples were analyzed in HPLC according to the procedure described below.[/fusion_text][fusion_text]

HPLC System: Water 2790 HPLC system, with PDA 996 detector (Waters).
Solvents: A: Water
B: Acetonitrile
Solid phase: LichroCART RP-Select B, 250-4 particle size 5µm, 250-4mm (Merek, Cat. No. 165018) at RT.
Gradient:
Time (minutes) A (%) B%
0 95 5
10 5 95
Injection Volume: 40 µl
Processing method: The data was processed using Millennium software. Processing wavelength was set to 273nm. The sample amount was calculated using derived calibration curves (see subsection 6.1).

[/fusion_text][fusion_text]Papp Calculations

An apparent permeability coefficient (Papp) of Caffeine was calculated from the following equation:

Equation 1

Papp(t) = (C1V / t)*(1 / C0A)

In which C0 is the initial concentration (at t = 0) of the compound on the donor (apical side) and C1 is the concentration at the calculated nine point (t) in the receiver chamber, V is receiver chamber volume, A is the surface area of the monolayer, and t is the elapsed time.

Caffeine Transport

The JetPeel device may facilitate the transport of drugs across skin. To determine if indeed drugs are transported faster with device treatment, we utilized a model hydrophilic drug – Caffeine.

In Caffeine transport experiment, 1mg/ml Caffeine solution replaced the water in the previous treatments. Following treatment, skin samples were stretched in diffusion chambers and Caffeine was loaded at their apical (air) side. Aliquots were removed at several time points from the basolateral (body) side of the diffusion chamber and analyzed for Caffeine concentration with HPLC (Figure 3). Permeability coefficients were subsequently calculated (Table 1).

Figure 3     Caffeine Treatment to Pig Skin samples

Caffeine was administered at the apical side of pig skin pieces with the JetPeel device (n=2 for treated and non-treated group). Samples were removed from the basolateral chamber at 0.5, 2, 6, and 20 hours following treatment, and analyzed in HPLC. Typical chromatogram and summery of individual raw data are presented in Appendix 1.

Caffeine concentration in mg/ml with standard deviation is plotted vs. transport time in minutes. Trendline regression is presented adjacent to each graph.

Caffeine in Basolateral Chamber

As can be seen in Figure 3, JetPeel treatment resulted in almost immediate increase, as early as 30 minutes, in Caffeine transport to the basolateral chamber. The higher Caffeine could be measured in the non-treatment samples.

These results demonstrate the ability of JetPeel device to cause Caffeine penetration into the skin, followed

by its immediate release at the other side.
Permeability of compounds is usually expressed as the flow of a compound through surface area. Thus, we calculated permeability coefficients (Papp) of Caffeine for each time point (Table 1).

Table 1     Caffeine permeability (Papp) following JetPeel device treatment
Permeability coefficients were calculated as described in Methods for each diffusion chamber at each time-point (Papp) is presented as average ±SD[/fusion_text][fusion_text]

Transport Time (hours) Papp (cm/sec x 106)
Caffeine-treated Non-treated
0.5 3.5 ± 0.6 0.0 ± 0.0
2 5.0 ± 1.3 0.0 ± 0.0
6 7.0 ± 3.1 4.0 ± 1.8
 20 33.4 ± 0.3 21.3 ± 0.5

[/fusion_text][fusion_separator style_type=”none” top_margin=”” bottom_margin=”30″ sep_color=”” border_size=”” icon=”” icon_circle=”no” icon_circle_color=”” width=”” alignment=”center” class=”” id=””/][fusion_text]Permeability (Papp) values of the Caffeine-treated skin samples are much higher although the experiment.
Papp values of Caffeine is non-treated skin are well correlated with its values in the literature (above 1×10-5).
An increase in Papp values along transport time with both treated and non-treated skin is observed. This phenomenon usually hints to active transport. We presume that the influence of Caffeine on transporters in the skin bring about this increase1.

*Harlan Pharmacological & Biological Monitoring Kiryat Weizmann, Rehovot, Israel
*Harlan Pharmacological & Biological Monitoring Kiryat Weizmann, Rehovot, Israel
4. Results Summary

In this reported study, JetPeel device treatment pressurized into the skin either oxygen with water, or oxygen with Caffeine.
The signal of oxygen released from skin tissue was not specific to JetPeel treatment probably due to high background signal from the tissue itself.
JetPeel Caffeine treatment resulted in an almost permeation of the compound. Caffeine high concentrations levels were maintained through the experiment.

5. Appendix 1

Caffeine Chromatogram

Chromatogram of 2µg Caffeine.

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Individual Sample

Reported by User: System
Project Name: Skin_transport[/fusion_text][fusion_text]

SAMPLE INFORMATION
Sample Name: Caffeine 0.2mg/ml Acquired By: System
Sample Type: Standard Date Acquired: 10/24/04 3:46:07 PM
Vial: 1:A,1 Acq. Method Set: Caffeine_5
Injection #: 1 Date Processed: 10/25/04 4:56:37 PM
Injection Volume: 10.00ul Processing Method: Caffeine_1
Run Time: 10.0 Munutes Channel Name: Wvln Ch1
Sample Set Name: transport_skin Proc. Chnl. Descr.: PDA 273.0 nm

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Peak Name RT Area % Area Height Amount Units
1 Caffeine 6.643 6363178 100.00 1141922 2,000 ug

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Individual Results Summary

Sample Summary

Reported by User: System
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Sample Name: Caffeine 0.2mg/ml Vial: 1:A, 1
Date Aquired: 10/24/04 3:46:07 PM Inj. #: 1

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Peak Name Processed Channel Retention Tine (min) Area % Area Height Amount Unit
1 Caffeine PDA 273.0 nm 6.643 6363178 100.00 1141922 2.0 ug

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Sample Name: C1 time0 Vial: 1:A, 4
Date Aquired: 10/24/04 5:25:35 PM Inj. #: 1

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Peak Name Processed Channel Retention Tine (min)
1 Caffeine PDA 273.0 nm 6.408

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Sample Name: C2 time0 Vial: 1:A, 5
Date Aquired: 10/24/04 5:36:44 PM Inj. #: 1

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Peak Name Processed Channel Retention Tine (min)
1 Caffeine PDA 273.0 nm 6.408

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Sample Name: #1 time0 Vial: 1:A, 6
Date Aquired: 10/24/04 5:58:58 PM Inj. #: 1

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Peak Name Processed Channel Retention Tine (min) Area % Area Height Amount Unit
1 Caffeine PDA 273.0 nm 6.489 1787106 100.00 142680 0.6 ug

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Sample Name: #2 time0 Vial: 1:A, 7
Date Aquired: 10/24/04 6:10:08 PM Inj. #: 1

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Peak Name Processed Channel Retention Tine (min) Area % Area Height Amount Unit
1 Caffeine PDA 273.0 nm 6.489 244220 100.00 20737 0.2 ug

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Results: The novel delivery system has shown effectiveness in improving the quality and texture of the skin, of improving acne vulgaris, and in the delivery of other important actives into the skin.

Conclusions: The JetPeel is a new, novel delivery system which s finding a place in dermatology.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_1″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]

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Lidocaine-Delivery System, EMLA 5% Comparable for Pain

BY DOUG BRUNK

FROM THE ANNUAL MEETING OF THE AMERICAN SOCIETY FOR LASER MEDICINE AND SURGERY

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Dr. Gold
The study involved patients who were scheduled for needling roller procedures for upper lip rhytids.
DR. GOLD

PHOENIX — Patients reported less or a comparable amount of pain during needling roller treatment for upper lip rhytids when lidocaine was delivered with a jet-phoresis system, compared with an application of EMLA 5% cream, results from a small study of 20 patients showed.

During a poster session that occurred at the meeting, researchers presented results from a study designed to compare ad-ministration of lidocaine with the jet-phoresis system with the topical cream for pain control in patients who were scheduled for needling roller procedures for upper lip rhytids.

For the study, Dr. Michael Gold, a dermatologist who practices in Nashville, Tenn., and Dr. Ram Burvin, a plastic surgeon who practices in Tel-Aviv, had patients serve as their own controls.

The mean age of the patients was 56 years, and all were female. The researchers treated half (left or right) of each patient’s upper lip with EMLA 5% cream for 45 minutes and the contralateral portion of the lip with lidocaine 3% jet phoresis for 5 minutes.

They used a visual analog scale to measure pain elicited by application of a needling roller across the patient’s upper lip.

Each patient again served as her own control 12-16 weeks later when the treatments (lidocaine 3% with jet phoresis vs. EMLA 5%) were repeated on the opposite lip sides for the same du-rations, so that in all, there were 40 full-lip applications of the two treatments.

Lidocaine 3% with jet phoresis and EMLA 5% were comparable in 19 applications. The jet phoresis system was better in 14 applications; EMLA 5% was better in 7 applications.

Different readings for the left and right sides were registered in some of the patients.

Of the total 40 treatments, pain control with lidocaine 3% with jet phoresis and EMLA 5% was comparable in 19 applications. Pain control was better with the lidocaine 3% with jet phoresis in 14 of the applications; it was better with EMLA 5% in 7 applications.

The delivery device, the jetPeel 3, uses pressurized gas at supersonic velocities to deliver saline or other liquid nutrients through special handpieces into the superficial layers of the skin.
The device was cleared by the Food and Drug Ad-ministration in 2006 for delivery of saline into the skin.

Disclosures: The researchers received honoraria from TavTech Ltd., maker of the jet-phoresis system, to conduct the study.

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Hydroporation With Jetpeel Dermalinfusion – An Analysis Of Efficacy

[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_text]Introduction

Beautyful skin causes in physical attractiviness. Therefore cosmetic procedures should optimize parameters like skin glow and elasticity.

Jetpeel is a device for cosmetic resurfacing of the facial skin. It is based on a technology of a 2-phase stream that creates a jet composed of high pressure air flux delivery, including oxygen, mixed with different chemical compounds sucand microdroplets of saline or for example antioxidants, vitamins and hyaluronic acid accelerated to supersonic velocities. This jet impacts the skin, causing gentle and accurate cosmetic peeling.

In this half side, randomized controlled split face trail we evaluated the effects of a new hydroporation method.

Methods & material

In this randomized, double-blind, half-side comparison of 6 weeks duration 20 healthy females (aged 20 – 45 years) with signs of skin aging were randomized to receive a treatment with a hyaluronic acid solution applied with the Jetpeel (figure 2) at one side of the face and a saline peeling at the contralateral side.

Efficacy was assessed at baseline and after treatment using a subject questionnaire. Additionally biophysical assessments of surface topography (Primos®, GFMesstechnik GmbH, Berlin, Germany), skin elasticity (Cutometer® MPA 580) and skin hydration (Corneometer® CM 825) were also performed. To evaluate the tolerance of the treatment pH-value (Skin-pH-Meter® PH905), transepidermal waterloss (Tewameter® TM 300, all Courage & Khazaka, Cologne, Germany) were performed and furthermore subjects were asked to keep a project diary. Pictures were performed by using Visia System (Canfield, Fairfield, USA)

Study Design

press-hwjd-1

 [/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]

Fig. 2: Treatment with Jetpeel

[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]Results

After 6 treatments using saline solution and delivering by hyaluronic acid with Jetpeel skin quality improved in all subjects. There was a clinical improvement of wrinkle severity according to the evaluation of skin topography. Skin netto elasticity increased by 14,8%, brutto elasticity by 4,8%. Skin surface hydration evaluated by corneometry improved from 63,64 to 65,05.

Results of the subject questionnaire showed a significant time effect for skin sensation (p = 0,005), skin glow (p ≤ 0,001), skin smoothness (p = 0,02) and skin hydration (p = 0,001). 95% of subjects were delight with the treatment. There were no reported side effects, moreover pH value and trans-epidermal waterloss remained in physiological range over the entire study period.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]Fig. 3: standardized fotography at a) baseline and b) after a six week treatment with Jetpeel[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]Fig. 4: standardized photography at a) baseline and b) after a six week treatment wih Jetpeela[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]Fig. 5: Results of facial appearance self-perception questionnaire (* p<0.05, **p<0.01, ***p<0.001)[/fusion_text][/fusion_builder_column][fusion_builder_column type="1_2" last="yes" spacing="yes" center_content="no" hide_on_mobile="no" background_color="" background_image="" background_repeat="no-repeat" background_position="left top" border_size="0px" border_color="" border_style="" padding="" margin_top="" margin_bottom="" animation_type="" animation_direction="" animation_speed="0.1" class="" id=""][fusion_imageframe lightbox="no" lightbox_image="" style_type="none" bordercolor="" bordersize="0px" borderradius="0" stylecolor="" align="none" link="" linktarget="_self" animation_type="0" animation_direction="down" animation_speed="0.1" hide_on_mobile="no" class="" id=""] [/fusion_imageframe][fusion_text]Fig. 6: Results of skin elasticity (arbitrary values)[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]Fig. 7: Results of corneometry (arbitrary values)[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_imageframe lightbox=”no” lightbox_image=”” style_type=”none” bordercolor=”” bordersize=”0px” borderradius=”0″ stylecolor=”” align=”none” link=”” linktarget=”_self” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ hide_on_mobile=”no” class=”” id=””] [/fusion_imageframe][fusion_text]Fig. 8: Results of skin topography a) at baseline, b) after six week of treatment[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_text]Conclusion

The evaluated cosmetic procedure proved to be an effective option for non-invasive application of hyaluronic acid. It improves skin glow, smoothness and hydration and is accombiened with a high subjects` satisfaction. Furthermore it s well tolerated.
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Histology Results Following JetPeel Treatment

Dr. Kyong-Chan Park Professor in Dept. of Dermatology at SNUH

Case

  • A male aged 59 years
  • Treated with Jet-M containing cosmetic preparation once a week for 12 weeks
  • Wrinkles around the treated eye were greatly decreased

histology-results-following-jetpeel-treatment-img1

Collagen fiber

  • H&E
  • Masson’s trichrome

histology-results-following-jetpeel-treatment-img2

Fibrillin-1

  • IF staining using antibody
  • Green: Fibrillin-1 (mouse Ab)

histology-results-following-jetpeel-treatment-img3

Procollagen type 1

  • IF staining using antibody
  • Green: Procollagen type 1 (mouse Ab)

histology-results-following-jetpeel-treatment-img4

Tropoelastin

  • IF staining using antibody
  • Green: Tropoelastin (rabbit Ab)

histology-results-following-jetpeel-treatment-img5

Results

By triple-jet treatment for 12 times with Skin-MD solution,

  1. Wrinkle is decreased around eye.
  2. Collgen amount is increased.
  3. Fibrillin-1 was also increased.
  4. Type 1 collagen was increased.
  5. Tropoelastin was increased.

Preliminary Clinical Study From 6 Volunteers

histology-results-following-jetpeel-treatment-img6

Results

By triple-jet treatment for 8 times with Skin-MD solution,

1) Melanin index was decreased significantly.

2) However, changes of erythema index (EI) was more significant.

Summary

Triple-jet treatment for 8 times with Skin-MD solution is effective not only in pigmentation but also in facial erythema.

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A State Of The Art Facial At Jet Concepts

By Amelia Chia | Categorized under style

a-state-of-the-art-facial-at-jet-concepts-compli

Rocket science and your skin? Pfft.

I’ve always been slightly wary of machines when it comes to my face because while technology works wonders on other things like hair and fat removal, I believe the face needs to be treated with special care. I have recurring nightmares of a mangled mug.

Well, to all you technology-savvy gentlemen out there, here’s another 21st Century wonder to add to your list. The Jet PureHyal facial is unlike any facial I’ve ever tried (and I’ve been a frequent facial patron for the last seven years).

At the ultramodern Jet Concepts spa, they take a different approach to treating your skin and producing optimal results. We’re used to the searing pain of extraction during normal facials and perhaps even the laser treatments at aesthetic clinics that promise to smooth out our skin. But what about something in between – a two-in-one that is both a facial and a non-invasive treatment but delivers results like you just stepped out of a $600 a pop session?

The Jet PureHyal Facial

The Jet PureHyal facial The Jet PureHyal facial starts with a thorough cleansing using the Jet-M machine, which tends to your skin with better precision than human hands.

“Jet-M performs four vital functions: it exfoliates, boosts lymphatic drainage, allows for effective infusion of active ingredients and provides extraction benefits,” says Gladys Cheng, the founder and CEO of Jet Concepts.

Developed by a Russian rocket scientist, the machine uses supersonic pressure to deliver actives to the skin for rejuvenation, with improvements on facial wrinkles, acne scars and rough skin.

Once the dead skin cells are sloughed away and your skin is brightened and prepped, pure hyaluronic acid is infused into your skin – without so much of an injection – but through carefully calibrated air-jets. For those who can only link acid to the chemistry lab, hyaluronic acid is touted to be a beauty enhancer which hydrates the skin and erases fine lines, wrinkles and saggy skin.

Believe me, you’ll be lulled to sleep during this one-hour facial. You won’t feel anything more than tiny pops of air bursting on your skin, and your therapist will kindly stick earplugs in your ears to drown out the noise from the machines. After which, she’ll slap on a cold mask to seal the hyaluronic acid into the skin and give you a solid head and shoulder massage. I dreamt that I was lying on a beach in Bahamas, and willed her in my mind to keep going.

This is one machine that certainly did the trick and didn’t leave me quivering. My skin appeared more radiant with a more even skin tone, and there was an immediate visible reduction of lines around the eye area.

Needless to say, I was an instant machine convert.

Price: $168 for a one-hour session

Location: Jet Concepts is located at #03-03 Wheelock Place or #B2-20/21 Raffles City Shopping Centre

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The Benefits Of Jet Peel Technology

randrpm-edelman-compli

Dr Michael H Gold, an internationally recognised, leading Dermatologist and Cosmetic Surgeon was recently invited by Kaya Skin Clinic to speak about the latest developments in skincare

“Jet Peel technology is the answer to the world’s need for non-invasive surgery,” says Dr Michael H Gold, as he begins to share the importance and benefits of this revolutionary technology, an interesting fact being that Jet Peel technology actually originates from the aviation principles. Dr Gold is a consultant for TavTech, the world leader and pioneer in the Jet Peel technology for aesthetic applications and skin conditions. In India the benefits of this technology come exclusively from Kaya Skin Clinic in its Aqua Radiance service.

“With Jet Peel technology, you can go 4.5mm into the skin without using a needle. That’s what makes the aqua radiance treatment so effective,” says Oren Gan, VP sales and Marketing at TavTech. “During the Aqua radiance treatment, the infusion hand piece is used to infuse glycolic acid or other drugs used to treat the person’s skin. Basically, this hand piece is able to create channels that needles can create.”

This Aqua radiance treatment is very beneficial for people with skin damage, acne and other skin problem. Depending on the intensity of your problem you could choose 6-8 treatments over 2-3 weeks, as your healthy, clear skin would emerge thereafter. A proper skin-maintenance regimen is highly beneficial thereafter with treatments in 2-3 month intervals.

“This treatment acts as a preventive measure for skin problems,” shares Dr Gold. “Fine lines on the skin, wrinkles, tanning, tired puffy eyes, pigmentation; all these are major issues that should be tackled to prevent early aging. Many Indian women suffer from these skin issues and thus will benefit a lot from this treatment.”

“In the last few years, the number of people choosing minimally invasive procedures has increased drastically. Botox, laser hair removal, chemical peels are being chosen by people for enhancing beauty. In the future, we hope to get rid of needles for minimally invasive procedures and instead use this technology, ” says Gan.

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Epidermal And Dermal Histological Characteristics In Response To Hydroporation

[fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_text]Keywords: Hydroporation, histology, wound healing, drug delivery, fractional laser

SUMMARY

BACKGROUND: Targeted drug deliver through an intact epidermal barrier is of interest in order to treat various skin conditions and diseases. Among many available methods hydroporation has already been shown to be effective for controlled skin rejuvenation by localized epidermal ablation. Therefore the concept might also be suitable to be used to trans-epidermal scarless deposition of substances, drugs or molecules using recently developed handpieces having nozzles smaller than 120 μm. However systematic studies investigating the tissue effects on those hydroporation systems are lacking.

OBJECTIVES: The aims of this in vitro study were (1) to prove the ability of the hydroporation system to penetrate the epidermal compartment and (2) to be able to deposit liquids (NaCl, vitamin a and c solutions), viscous substances (hyaluronic acid), crystalloid suspensions (triamcinolone, 40 mg/ml), and molecules of higher molecular weight like antibodies
(IgG-FITC), PEG’s (FITC-PEG’s) and sugars (Dextrane-FITC) into the dermis using an skin explant model with and without AFXL pre-treatment using two different types of ablative fractional lasers.

MATERIALS AND METHODS: Skin explants were subjected to hydroporation using alcian blue inked 0.9 % NaCl, unstained 0.9 % NaCl applications for 10 s, 30 s, 1 min, ready to use solutions containing vitamin a and c as well as hyaluronic acid crystalloid suspensions, antibodies, heterofunctionalized polyethylene glycol and sugars to investigate morphological tissue changes and to measure distribution within the epidermis and the dermis. To test the potential synergistic effect of fractional ablative laser pre-treatment in conjunction with hydroporation to apply molecules of higher molecular weights two laser systems have been used.

RESULTS: The hydroporation system has been tested for effective deposition of low molecular weight particles in a homogenous distribution up to a dermal depth of 1436 μm. Furthermore hyaluronic acid of low viscosity and crystalloid suspensions could be placed into the dermis of normal skin. In cases of dense collagen fibers as seen in scars deposition was limited. The transport of high molecular weight substances (2, 70, and 150 kDa) was possible through the nozzle of a standard handpiece, however epidermal penetration was limited. Pre-treatment with either a fractional ablative CO2- or Er:YAG-laser enabled deep dermal deposition of those molecules.

CONCLUSION: This in large vitro study clearly demonstrated that the hydroporation concept can be applied to human skin in a safe and effective manner not only for controlled ablation but also for scarless dermal application of low molecular weight molecules in liquids of low and medium viscosity. The application of high molecular weight compounds was made possible by pre-treating the skin with fractional ablative lasers.[/fusion_text][fusion_text]

TAB. 1: OVERVIEW OF CURRENT TECHNOLOGIES TO PENETRATE THE EPIDERMAL BARRIER [13].
Designed Topicals Chemical & Mechanical Penetration External Forces TOR – Temporarily Opened Epidermal Barrier
SupersaturationPenetration enhancer

Encapsulation

Nanocarriers

SyringesSuction blisters

Dermabrasio

Peeling

IontophoresisSonopheresis

Electroporation

Photomechanical waves

Hydroproration

Laser microjet

DermarollerFractional ablative Laser & RF-devices

Fractional non-ablative qs

Laser

High limitation to size of compound & transport capacity Limitation to area and depth  penetration & transport capacity Limitation to size of compound & transport capacity 50 % of skin can be opened without scar formation for 24hPotentially high capacity but inside out pressure gradient

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Introduction

The human skin, the largest organ surface wise has been attractive for topical and transdermal intervention since ever. However, Evolution has designed a very efficient barrier preventing human beings from water loss, penetration of germs, allergens poisons, toxins, radiation and other influences of danger in a very sufficient manner. To overcome the barrier many concepts have been developed (Tab. 1).

Recent insights to the potential of fractional skin treatments have established standard laser procedures to treat aged and sun damaged skin and scars. The biggest potential of it is foreseen with the option of a contact free temporary opening of the epidermal barrier (TOR, German: gate) to promote new and intensified treatment regimen. Fractionated laser therapies are routinely used in the clinic to treat scars and many other conditions [1]. By treating the skin with fractions, a response is initiated that involves the skin replacing itself in up to 50 % of the surface if the individual piece of skin removed is smaller than ~0.3 mm in diameter. These columns of treated skin can reach as deep as the dermal compartment and are called microscopic treatment zones (MTZ or microscopic ablation zones (MAZ)) [2–4]. In recent years, experimental in vitro and in vivo studies have proven that treatment with AFXL enhances the uptake of topically applied small molecules like photosensitizers and facilitates distribution into deep skin layers [5–9].[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_3″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]

The triple nose handpiece
Fig. 1: The triple nose handpiece ensures a larger treatment area while dividing the fluid stream into three.

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The standard single outlet handpiece
Fig. 2: The standard single outlet handpiece ensures the most powerful application mode of a stream accelerated up to app. 750 km/h.

[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_3″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]

The prototype handpiece
Fig. 3: The prototype handpiece with a backpack like opening for standard vials was used to test liquids having a higher viscosity. The system displayed does also have a triple outlet.

[/fusion_text][/fusion_builder_column][fusion_builder_column type=”2_3″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]Among the use of external forces (Table 1) hydroporation has gained a new interest since the development of highly effective devices. It has been effectively used for lymph drainage, gentle massage and also facial rejuvenation [10]. In the latter setting the system was able to ablate of the epidermis in a controlled manner. Interestingly there were no disturbances of wound healing. However, as in traditional laser concepts aiming on full thickness epidermal ablation erythema, herpes virus infection, crusting and emphysema have been reported [10].

Hydroporation however may also ensure a contact free drug delivery approach together with the use target molecules within a jet stream at high speeds to treat large surface areas. This concept avoids epidermal ablation despite the possible application of high volumes or substance concentrations. However systematic studies investigating the tissue effects on those hydroporation systems are lacking. So far it is not known what type of penetration injury takes place and if at all a substance or drug is deposited to the deeper structures of the skin. Of importance is to know penetration depth and delivery capacities in relation to substance viscosity, molecule size and tissue properties.

The aims of this in vitro study were (1) to prove the ability of the hydroporation system to penetrate the epidermal compartment and (2) to be able to deposit liquids (NaCl, vitamin a and c solutions), viscous substances (hyaluronic acid), crystalloid suspensions (triamcinolone, 40 mg/ml), and molecules of higher molecular weight like antibodies (IgG-FITC), PEG’s (FITC-PEG’s) and sugars (Dextrane-FITC) into the dermis using an skin explant model with and without AFXL pre-treatment using two different types of ablative fractional lasers.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_3″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]

Visualization of distribution type and depth of ink stained
Fig. 4: Visualization of distribution type and depth of ink stained 0.9 % NaCl solution stained with blue ink (patent blue). Without displaying a gross damage on the epidermis the ink is homogenously distributed in an area of 693 μm width and up to 1024 μm depth.

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Materials and Methods

A prospective, single-center, in vitro study was designed to examine morphological changes visible at microscopically as performed in earlier studies [11, 12]. The study protocol used a previously described model and conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Skin samples, obtained at routine skin surgery, were used as skin explants. All subjects consented the use of their skin explants.

Hydroporation

Hydroporation was performed using the system JetPeel™-3 System (TavTec, Israel) in conjunction with two out of the available applicator systems (triples nose, single nose, Figure 1 and 2) and a specific prototype made for application tests (name?). The hydroporation system ensures a fluid stream accelerated up to 720 km/h.

Laser System

AFXL was performed with a 10,600 nm CO2 laser (Exelo2, former Quantel-Derma now Alma Lasers GmbH) and a 2,940 nm Er:YAGLaser (Burane FXL, former Quantel-Derma GmbH now Alma Lasers GmbH, optic lens array FX12).

The fractionated CO2-laser was operated with a scanner, using a spot diameter of 250 μm. The pulse duration (exposure time) was 1 ms, and the pulse energy of 40 mJ was delivered by 1 stack and 1 pass at a density of 250 MAZ /cm2. The average fluence in each MAZ generated by a scanner was 81.6 J/cm2 (spot area 0.049 mm2; 40 mJ / 0.049 mm2 = 0.04 J / 0.00049 cm2 = 81.6 J/cm2). The average fluence with the treatment area is calculated as 40 mJ * 250 MAZ/cm2 = 10,000 mJ/cm2 = 10 J/cm2.

The fractionated Er:YAG-laser was operated with a FX12 optic a lens array, density of 270 MAZ /cm2, providing a spot diameter of 150 μm. The laser was set to 31.8 mJ pulse energy with a 300 ms pulse duration (exposure time), consisting of 10 stacked subpulses of 3.18 mJ each. The average fluence with the treatment area is calculated as 31.8 mJ * 270 MAZ/cm2 = 8,586 mJ/cm2 = 8.6 J/cm2. Therefore the average fluencies in each treatment areas are comparable, despite differences in absorption characteristics.

Skin explants

Skin explants were subjected to hydroporation (JetPeel™-3 System, TavTec, Israel) using (1) alcian blue inked 0.9 % NaCl, (2) unstained 0.9 % NaCl applications for 10 s, 30 s, 1 min, (3) ready to use solutions containing vitamin a and c as well as hyaluronic acid (4) crystalloid suspensions (triamcinolone), (5) proteins (IgG-FITC, goat anti-mouse IgG-FITC, average molecular weight ~ 150,000, Santa Cruz Biotechnology, cat# sc-2010), (6) FITC-PEG’s (Fluorescein hetero-functionalized polyethylene glycol, MW 2000, cat# PEG4-0002, mPEG-FITC, Nanocs, www.nanocs.com) and (7) sugars (Fluorescein isothiocyanate-dextrane, Dextrane-FITC, average molecular weight 70,000, Sigma cat# 46945) to investigate morphological tissue changes and to measure distribution within the epidermis and the dermis. To test the potential synergistic effect of AFXL in conjunction with hydroporation skin explants were fist subjected to AFXL as described above and then hydroporated using test substances of higher molecular weight (8) IgG-FITC, FITCPEG’s and Dextrane-FITC.

Routine Pathology Workup

Each skin sample was subjected to 4 % buffered formalin post intervention. Following fixation in formalin, all skin explants were embedded into paraffin, sectioned into 4 μm to 6 μm thick slices and stained with hematoxyline and eosin and alcian according to in-house routine protocol. Only samples treated with inked NaCl were processed without H&E and alcian staining.

Immunofluorescence

The tissue sections were frozen and sectioned into 5–8 μm thick slices. Slides were the analyzed using the fluorescence microscope using different magnifications (Olympus BX41, Germany, magnification: 1.25, 4, 10, 20, 40, 60, 100x) and documented using a calibrated digital camera system (Olympus DP71, Germany) together with the software evaluation package (Olympus Cell F, Germany). Fluorescence microscopy enabled visualization of FITC-labeled antibodies, PEG’s, and antibody distribution in detailed areas of skin the sections before and after hydroporation alone or following ablative fractional laser treatment.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_4″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”solid” padding=”” margin_top=”” margin_bottom=”” animation_type=”0″ animation_direction=”down” animation_speed=”0.1″ class=”” id=””][fusion_text]

Hydroporation
Fig. 5: Hydroporation does not lead to any morphological changes within the epidermis or dermis. In comparison to untreated controls superficial parts of the stratum corneum only have been removed.

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Hydroporation
Fig. 6: Hydroporation over 30 s in a defined area led to vacuole formation, removal of the stratum corneum and circumscribed epidermal loss. Localized separation of dermal fibre bundles are visible.

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Hydroporation
Fig. 7: Hydroporation over 60 s in a defined area led to a complete loss of the epidermis, dermal vacuole formation, and localized separation of dermal fibre bundles.

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Hydroporation
Fig. 8: Using ready to use solutions containing vitamin a provided by the manufacturer a rather uniform vacuole formation, spreading of dermal fibers within the full depth of dermis up to 1436 μm was measurable. However in some areas there was also a complete destruction of the dermal fiber structure visible.

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Results

The investigation of the general ability of the Jetpeel hydroporation system to interact with epidermal and dermal human structures was first tested by the application of stained 0.9 % NaCl inked with alcian blue. The test application was performed using the single outlet handpiece with a mean application time of 10 s per area of app. 1 cm2. The histological slides reveal a homogeneous distribution of the ink which was also visible macroscopically within the upper two thirds of the dermal compartment leaving the epidermis on microscopical level intact. Interestingly only remnants of ink were detectable at the explants surface (Fig. 3).

To further test the safety and efficacy of the hydroporation system over time of application, unstained 0.9 % NaCl has been applied using the triple outlet handpiece for 10 s, 30 s and 60 s in a defined surface area of app. 1 cm2. As control served massage application in the same area size according to the instructions of the manufacturer. H&E stained slides revealed no epidermal or dermal changes using the so called massage application. In comparison to untreated controls superficial parts of the stratum corneum only have been removed (Fig. 5). When hydroporation was done over a time period of 10 s vacuole formation within the upper thirds of the dermal compartment appeared. Extending this time up to 30 s vacuoles increased in size (Fig. 6). Localized separation of dermal fiber bundles was visible. On top of this, in circumscribed areas there was a complete loss of the epidermis. Extending the application time to one minute revealed a total loss of the epidermal compartment (Fig. 7) as described earlier [10].[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]

Fig. 9
Fig. 9: If the provided hyaluronic acid in low viscosity condition as provided by the manufacturer was applied in the same way equivalent distribution pattern could be achieved as visualized in light blue color by alcian blue staining. Most probably depending on application pattern a predominant vacuole formation or a more in between the fibers deposition pattern was visible.

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Fig. 10
Fig. 10: Microscopy of a scarred tissue explant subjected to triamcinolone hydroporation. The tissue section reveals a homogenous deposition of the drug within the dermis. However denser scar tissue has not been penetrated (H&E). On top of this there was a higher tendency of an epidermal damage.

[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][fusion_text]In a third step of experimentation ready to use solutions containing vitamin a and c as well as hyaluronic acid provided by the manufacturer have been applied to skin explants in order to estimate the distribution of within the dermis and to measure maximum penetration depths. Using those solutions and applying them according to the instructions of the manufacturer in skin explants after standard histology work-up a penetration up to 1436 μ m was visible while there was a more or less uniform vacuole formation pattern and spreading of the dermal compartment visible (Fig. 8). There were no major differences visible if vitamin a or vitamin c solution were in use. If the hyaluronic acid of low viscosity condition as provided by the manufacturer was applied in the same way, equivalent distribution pattern could be achieved visualized by alcian staining. Most probably depending on application pattern a predominant vacuole formation or a more in between the fibers deposition pattern was visible (Fig 9 a+b). Interestingly with increasing viscosity there was no more pronounced epidermal damage visible on a microscopic level. As control a classical syringe based filler has been used. There was a clear dermaland subdermal deposition of an opaque material visible. Volume wise the filler application was much higher than that of the hydroporation system.

To further test the limits of the system and to answer the question if the concept may be also translated into clinics a crystalloid suspension (triamcinolone) as in use for clinical scar treatment has been applied to skin explants bearing scars using the prototype handpiece. Interestingly hence the sizes of the crystals is much smaller that the nozzle size of 120 μ m the triamcinolone particle could be transported via stream through the nozzle. Microscopy revealed a homogenous deposition of the drug with the dermis. However, the power of the system was clearly insufficient to penetrate the denser scar tissue (Fig. 10). To date trans-dermal drug delivery assisted by fractional laser is of extreme importance. Therefore the ability of the system to transport fluorescence labelled molecules like antibodies (IgG-FITC), PEG’s (FITC-PEG’s) and sugars (Dextrane-FITC) have been tested while using the prototype handpiece. Fluorescence microscopy revealed no significant deposition of the high molecular test substances PEG and the IgG antibody using the hydroporation system only. Only some deposition was visibly applying the sugar (Fig. 11 a–c). Hence the method of AFXL is now widely used to enhance dermal drug delivery in daily clinics, two laser systems were used to facilitate the hydroporation induced uptake of high molecular substances (Fig. 12 a–c). Pre-treatment of both laser systems resulted in an enhanced deposition of all high molecular weight test molecules within the MAZ and also the coagulation zone made by the CO2-Laser. If an Erbium laser was used the deposition within the dermis was less intense around the MAZ most probably due to the fact of a lower residual thermal damage.

Immunofluorescence
Fig. 11: Immunofluorescence of penetration capacity of hydroporated IgG-FITC (Fig 11a), FITC-PEG’s (Fig 11b) and Dextrane-FITC (Fig 11c) without laser pre-treatment.
Discussion

The investigation of the general ability of the Jetpeel hydroporation to penetrate the stratum corneum and the epidermal compartment in order to deposit liquids and small molecules by using an jet stream of liquids accelerated by pressure up 720 km/h through an very small singular or triple nozzle revealed by using inked 0.9 % NaCl a homogenous localized dermal deposition in unstained tissue slides made of human skin explants.

Hence the amount of liquid applied to a given surface area is strongly operator dependent, the safety of the massage procedure as suggested by the manufacturer has been tested successfully. According to the H&E slides a very superficial removal of the stratum corneum was visible only. However, extended application times resulted in first vacuole formation, lateral spreading of collagen fibers and finally complete loss of the epidermal compartment as known from previous studies [10]. These findings suggest that precise operator skills are necessary for optimal effects and homogenous deposition of substances using the system. The experimental design using skin explants and inked NaCl might provide a cheap an easy training setting hence coloration is visible by the naked eye. Furthermore, states of the art of after care professional assistance of wound healing are required in case of epidermal damage. As known from laser procedures, precautions may be set in place e.g. herpes prophylaxis, sunscreen, down time and post treatment regimen.

The manufacturer does provide a variety of ready to use liquids containing for example vitamin a and c as well as hyaluronic acid of low viscosity for dermal treatments. The question arose if at all and how deep those substances may penetrate and what the distribution pattern looks like. There were no major differences of distribution type and depths visible if vitamin a or vitamin c solution were in use. The total penetration depth was measured as 1,436 μ m while preventing a major epidermal collateral damage. In case of the hyaluronic acid which does
certainly excels a higher viscosity similar distribution types and patterns were visible on a microscopic level.

In an experimental set-up using the prototype handpiece mounted with a matching vial containing a standard solution of triamcinolone 40 mg/ml as clinically used for scar treatments the hydroporation concept has been tested if crystalloid suspension also may be applied to healthy and scarred tissue. Microscopy revealed a rather homogenous deposition of the drug within physiological tissue while dense scar tissue was almost not penetrated. It is therefore concluded that small insoluble particles in liquid might be transported by the system, however penetration capacity is limited if texture density increases.

Immunofluorescence
Fig. 12: Immunofluorescence of penetration capacity of hydroporated
IgG-FITC (Fig 12a), FITC-PEG’s (Fig 12b) and Dextrane-FITC (Fig 12c)
using a CO2- ablative fractional laser pre-treatment.

Another potential limitation of the system is assumed if high molecular molecules shall be applied. Hence their application would of clinical interest three test molecules were used to test the transportation capacity and the ability to get those molecules deposited to the dermis. The experimental design was made by using fluorescent labelled antibodies, PEG’s and dextrane. Using the hydroporation alone it has to be concluded although transported onto the skin surface there was a limited penetration visible for the dextrane only. Moreover in conjunction with an AFXL pretreatment however this limitation could be overcome clearly.

There are several limitations of the study that warrant attention. First those results gained in-vitro may not directly apply to clinical settings. Especially the experimental design does not allow the exact calculation of how much of the potential drugs can be transported into the skin. Finally it remains open, to test if potentially applied drugs, molecules or substances tolerate this mechanism of transportation without change or loss in function or biological properties. These might be especially the case in large size proteins like antibodies.

Conclusion

This in large vitro study clearly demonstrated that the hydroporation concept can be applied to human skin in a safe and effective manner as long as a well-trained operator follows the instructions of the manufacturer. Hence the jet stream is accelerated to enormous speeds liquids containing active substances as well as hyaluronic acid having a higher viscosity can be transported. Even small insoluble particles may be placed into the dermal compartment. However, penetration capacity is limited if texture density increases as it is the case in scars. Also due to the fact of the very high pressure acting on the epidermis inappropriate use of the system might lead to epidermal damage or complete loss of it resulting in wounding. Therefore appropriate after care needs to be provided. Hence hydroporation would be a very nice contact free application method in a wide clinical setting e.g. vaccination, topical biological therapy and many more the transport and deposition capacity of the system has been tested using antibodies, a PEG’s and dextrane. Although still being transported via the nozzle the penetration into the dermis was limited. A second approach using two different fractional ablative laser pre-treatment protocols at standard settings revealed again a sufficient dermal deposition.

Taken together this large in vitro study clearly shows the potential and limitation of the concept of hydroporation. Further clinical trials shall be performed to confirm these in-vitro findings.[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”no” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]Financial disclosure / Acknowledgments
Uwe Paasch received unrestricted research grants from Quantel-Derma GmbH, Nurnberg, Germany and Laserwelt GmbH, Berlin Germany.
Uwe Paasch served as consultant for Quantel-Derma GmbH, now Alma Lasers GmbH, Nurnberg, Germany.
The JetPeel V3 was loaned from Laserwelt GmbH, Berlin Germany.
[/fusion_text][/fusion_builder_column][fusion_builder_column type=”1_2″ last=”yes” spacing=”yes” center_content=”no” hide_on_mobile=”no” background_color=”” background_image=”” background_repeat=”no-repeat” background_position=”left top” border_size=”0px” border_color=”” border_style=”” padding=”” margin_top=”” margin_bottom=”” animation_type=”” animation_direction=”” animation_speed=”0.1″ class=”” id=””][fusion_text]Address of Correspondence:
Uwe Paasch, M.D., Ph.D.
University of Leipzig, Department of Dermatology, Venereology
and Allergology
Philipp-Rosenthal-Strase 23
D-04103 Leipzig
uwe.paasch@medizin.uni-leipzig.de
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