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Electroporation. New Delivery of Cosmetic Actives to the Skin

Electroporation or needless mesotherapy device seeks to do the same as injection mesotherapy, such as skin rejuvenation, whitening, acne, hair re-growth, localized fat reduction, and cellulite treatment. It uses a pulsed low-frequency current, whose intensity is adjusted by the operator. It delivers a particular waveform that ionizes the molecules in the active ingredients used in the treatment and creates tiny channels in the skin for the elements to travel down. Ingredients in water-soluble molecules permeate the skin's natural lipid barrier and then cascade through the tissue beneath via minute channels to penetrate the surface up to 9 -10cms and introduce 90% of the active ingredients being administered. This pain-free option is said to offer a practical mesotherapy alternative for needle-phobic.
NO NEEDLES MESOTHERAPY OR ELECTROPORATION

What is Electroporation?

Electroporation or (no-needle mesotherapy) device seeks to do the same as injection mesotherapy. It is used in skin rejuvenation, whitening, acne, hair re-growth, localized fat reduction, and cellulite treatment. It uses a pulsed low-frequency current, whose intensity is adjusted by the operator.

It delivers a particular waveform that ionizes the molecules in the active ingredients used in the Treatment and creates tiny channels in the skin for the elements to travel down. Ingredients in water-soluble molecules permeate the skin’s natural lipid barrier and then cascade through the tissue beneath via minute channels to penetrate the surface up to 9 -10cms and introduce 90% of the active ingredients being administered. This pain-free option is said to offer a practical mesotherapy alternative for needle-phobic.

Percutaneous Delivery of Cosmetic Actives to the Skin

Introduction

Recent developments in modern technologies combined with new knowledge in skin biology have advanced innovations in skin availability of actives and novel methods of substance delivery.

The basics

Percutaneous delivery aims to provide good action to the skin target site and optimize efficacy while minimizing side effects. It can achieve skin absorption by understanding the skin’s complex structure and relying on vehicles’ physical and chemical parameters applied to the skin.

Skin physiology

There are defined compartments and biological structures within the skin that provide opportunities to deliver actives. Within these compartments, many chemical and biological processes at work may alter a given activity or the physiology of the skin target.

TRANSDERMAL DRUG DELIVERY SYSTEM OR TDDS

The main barrier to active permeation through the skin is the stratum corneum. This structure is located at the outermost layer of the epidermis. The active must cross this skin barrier and permeate trans-epidermally to be delivered to the target site, and the secretion activity of the appendages can moderate the penetration.

It can deliver hydrophilic substances through the sweat gland route; however, this is also minimal in total volume. Therefore, the principal pathway for the skin penetration of actives is the trans-epidermal route. This trans-epidermal route can be further subdivided into transcellular and intercellular routes.

Active composition

One of the first steps in understanding the phenomenon of active delivery is to characterize the activity intended for delivery to the skin. There are well‐known physical and chemical parameters specific to all chemical compounds. As a rule, molecules with a molecular weight of less than 500 Da penetrate the skin better than molecules with a more considerable molecular weight. It is also known that the net charge is vital in enhancing penetration.

Novel formulation strategies allow manipulation of the partition coefficient (K) and concentration (C). The following strategies can enhance skin penetration:

  • Increasing drug diffusion in the skin
  • Increasing drug solubility in the skin
  • Increasing the degree of saturation of the drug in the formulation

Penetration enhancers

Topically applied chemical agents (surfactants, solvents, emollients) are a well‐known technique to modify the stratum corneum and the chemical potential of selected actives. These materials can be referred to as penetration enhancers (PEs).

Chemical enhancers are also known as absorption promoters and accelerants. Chemical enhancers are inert, non-toxic, non-irritating, non-allergic, fast, inexpensive, and cosmetically acceptable.

Physical enhancers stand between chemical enhancers and penetration enhancer devices. This unique classification is because, in most cases, the materials are particles of chemical origin but require physical energy to exert an action on the skin. These materials are used to debride or excoriate the stratum corneum by abrasive action physically by rubbing the particles by hand on the skin. New high-tech devices that propel an abrasive against the skin are now available, stripping away the stratum corneum.

Penetration enhancement vectors (vehicle) allow enhanced penetration via their small size and unique physical-chemical composition (liposomes, noisome, lipid particles, and nanocapsules).

Devices for penetration enhancement

Devices for enhancing skin penetration of actives are at the leading edge of skincare technology.

The topical application of pharmaceutical agents is a fundamental principle of dermatological therapy. However, the valuable barrier function of the skin significantly impairs the bioavailability of most topical drugs. Many pharmaceutical substances are too hydrophilic or too large (> 500 kDa) to permeate the stratum corneum at relevant concentrations and therefore must be encapsulated in liposomes, injected, or administered systemically.

Apart from a chemical modification of active substances or their vehicles, transdermal delivery of external chemicals has been aided by physical methods such as microneedles, iontophoresis and electro-osmosis, electroporation, laser, radiofrequency, and ultrasound. The local increase in temperature increases blood flow, and in turn, the rate of permeation/transport of active substances into the skin increases. This technique has the advantage of not employing a chemical, is non-invasive, and does not require activating a self-repair mechanism by the skin.

Abrasion techniques involve the direct removal or disruption of the upper layers of the skin to facilitate the permeation of topically applied medicaments. Some of these devices are based on techniques used by dermatologists for superficial peel resurfacing (e.g., microdermabrasion) in the treatment of acne, scars, hyper-pigmentation, and other skin blemishes.

Ultrasound involves ultrasonic energy to enhance the transdermal delivery of solutes either simultaneously or via pre-treatment and is often referred to as sonophoresis or phonophoresis. Ultrasound has been shown to improve transdermal transport of low molecular weight drugs (<500 Daltons) across human skin.

This method’s higher transdermal transport is attributed to cavitation induced inside or outside the skin. In addition, oscillations of cavitation bubbles result in significant water permeation into disordered lipid regions and lead to the formation of aqueous channels in the intercellular lipids of the stratum corneum.

Ultrasound parameters such as treatment duration, intensity, and frequency are all known to affect percutaneous absorption, with the rate being the most important. Although frequencies between 20 kHz–and 16 MHz have been reported to enhance skin permeation, frequencies at the lower end of this range (<100 kHz) are believed to significantly affect transdermal drug delivery macromolecules molecular weight up to 48 kDa. The proposed mechanism behind the increase in skin permeability is attributed to the formation of gaseous cavities within the intercellular lipids on exposure to ultrasound resulting in disruption of the SC.

Patches

Delivery patches have been available for some time. One of the first applications of patch technology was in a transdermal motion sickness (scopolamine) patch. There are commercial products that provide actives in a patch formula. They utilize adhesive technology or a rate‐limiting porous membrane to target and localize the actives. Some typical patch applications are directed toward reducing age spots or dark circles under the eye. The critical delivery enhancement for patches combines localized delivery and occlusion.

Iontophoresis

Iontophoresis is a technology that has been brought to the cosmetic industry via the pharmaceutical development field. Iontophoresis passes a small direct current through an active-containing electrode placed in contact with the skin, with a grounding electrode to complete the circuit.

  • The driving electrode repels oppositely charged species. Three important mechanisms enhance transport:
  • The electric current increases skin permeability; and
  • Electro-osmosis moves uncharged molecules and large polar peptides.

There are limitations related to this technique. The active ingredient must be water‐soluble, ionic, and with a molecular weight below 5000 Da. Despite all these limitations, reported data show that the effectiveness of drug delivery can be increased by one‐third through iontophoresis.

Understanding the skin and its interaction with various actives allows the chemist to select delivery options that provide safe and practical properties. Many formulation options are available for delivering actives to targets within the skin. A good understanding of the physicochemical parameters of the active and the desired skin target is needed before deciding on a particular delivery option.

Microneedles

Another type of delivery device is the microneedle. Microneedles are similar to traditional needles but are fabricated at the micron size. They are generally one μm in diameter and range from 1–100 μm in length.  The microneedle delivery system is not based on diffusion as in other transdermal drug delivery products but on the temporary mechanical disruption of the skin and the activities within the epidermis, where it can more readily reach its site of action. Microneedles have been fabricated with various materials such as metals, silicon, silicon dioxide, polymers, glass, and other materials. There are already patents granted for these types of moderately invasive delivery systems.

Multiple lasers have been used to improve skin penetration for drugs. Laser modalities include ablative skin resurfacing (ASR), non-ablative dermal remodeling (NDR), and fractional photo-thermolysis (FP). Laser treatment is often used for dermatological conditions such as acne and confers “facial rejuvenation,”

The laser radiation destroys the target cells over a short frame of time (∼300 ns). Direct and controlled exposure of a laser to the skin results in the ablation of the SC without significantly damaging the underlying epidermis. Removal of the SC via this method has been shown to enhance the delivery of lipophilic and hydrophilic drugs.

Fractional ablative lasers are an innovative strategy to overcome the epidermal barrier standardized and contact-free. The bioavailability of topical agents can be significantly enhanced using laser-assisted drug delivery (LADD).

Ablative fraction radiofrequency (AFR)-assisted drug delivery is a promising tool for the future of dermatology. We expect several agents to be paired with AFR for enhanced drug delivery. Radiofrequency thermal ablation has been used highly for electrosurgery and ablation of malignant tissues.

This involves exposure of skin to high-frequency alternating current (∼100kHz) and results in heat-induced microchannels in the membrane, like when laser radiation is employed — radiofrequency-induced microchannels stay open for less than 24 h.

How does Electroporation Treatment Work?

Iontophoresis and electroporation represent electrically assisted, physical approaches to enhancing the delivery of drugs/macromolecules across the stratum corneum. Iontophoresis uses low currents applied for minutes to hours from an externally placed electrode (with the same charge as the drug) in order to drive these molecules across the stratum corneum, primarily by electrophoresis.

As the rate of drug delivery is generally proportional to the applied current, iontophoresis offers an opportunity for programmable drug delivery, especially with the recent development of miniaturized microprocessor systems.

Clinically, iontophoresis has been employed to deliver: fentanyl and lidocaine for pain relief, pilocarpine to induce sweating (as a diagnostic test, and tap water to treat hyperhidrosis. Reverse iontophoresis has been used to extract glucose from the skin as a means of monitoring glucose levels in diabetic patients.

Electroporation (electropermeabilization) utilizes very short (microsecond to the millisecond) and relatively high voltage (~100 V) electrical pulses to induce structural rearrangement of stratum corneum lipids, leading to pore formation. Properly designed systems can minimize sensations from the pulses and facilitate delivery, especially of hydrophilic and charged molecules into the skin. Although only at the
research stage with regard to transdermal delivery, electroporation is currently being used to drive chemotherapeutic agents into superficial skin tumors by applying surface or penetrating electrodes6

The actual preparation injected during mesotherapy depends upon the problem being treated. In general, the substances used can include local anesthetics and products that may reduce inflammation, muscle relaxants, enzymes, vitamins, minerals, plant extracts, growth factors, hormones, and hormone blockers, to name but a few.

When used in the Treatment of aging skin, mesotherapy aims to replace minerals, vitamins, and amino acids found in lower levels in the skin as we age. It is also used to boost levels of hyaluronic acid, another essential part of the skin that helps keep up firmness and texture, which decreases as skin ages. It is claimed that injecting more hyaluronic acid just below the skin’s surface helps to stimulate more collagen production, which, in turn, improves skin tone and helps reduce fine lines and wrinkles.

Electroporation is a pain-free option that offers practical mesotherapy. It is considered an alternative for those patients that are needle-phobic. Electroporation enhances the penetration of active cosmeceuticals. It overcomes the protective barrier layers of the skin’s surface using mild electrical currents. Thus, aiding the transportation of the substance between the skin cells.

Electroporation or needless mesotherapy-10
no-needles-mesotherapy-or-electroporation10

The technique of electroporation or electrical transdermal delivery, whereby the substance being used to treat the area is ionized (i.e., the molecules within it are given a positive or negative charge) using galvanic current, has been developed since the first discovery in the 1700s.

The electroporation method uses the natural repulsion and attraction properties generated by positive and negatively charged agents when an electric current is applied to the substance in contact with the skin to repel the ingredients into the depths of the skin. Earlier techniques suffered poor skin penetration abilities (often much less than ½cm), despite their ability to carry high concentrations of active ingredients and required polarized substances (i.e., ones with already charged molecules).

The head of the electroporation device is similarly charged to the ionized molecules, and as it moves across the surface, it repels the molecules deep into it. Ingredients in water-soluble molecules permeate the skin’s natural lipid barrier and then cascade through the tissue beneath via minute channels to penetrate the surface up to 9 -10cms and introduce 90% of the active ingredients being administered.

What Can Electroporation Treatment Do?

Electroporation seeks to do the same aim as injection mesotherapy. It thus is targeted at the same treatment indications, such as skin rehydration and toning, as well as cellulite and fat reduction treatments. At MSI, we offer different electroporation treatments for the face and body. We use various actives o treat vitiligo, acne, hyperpigmentation, sensitive areas whitening, and hair loss.

What Happens During Electroporation Treatment?

I should also take a medical history to ensure that there are no reasons you shouldn’t undertake treatment. You may be asked to sign a consent form, which means that you have understood the potential benefits and risks associated with the procedure. The practitioner may also take photographs for a “before and after” comparison.

Electroporation Treatments feel like a ‘pins and needles’ sensation but are described as comfortable. It allows pulsed frequency electric current to deliver active ingredients into the skin. Electroporation treatment sessions are carried out once a week and last about half an hour each. You should usually see changes within a couple of sessions, but 7 is the average number of suggested treatments. Monthly electroporation maintenance sessions are then recommended afterward to maintain the results.

How Long Will It Take to Recover from Electroporation Treatment?

No recovery time is required, and you can return to work or normal activities immediately after treatment.

What are the Risks of Electroporation Treatment?

Electroporation is almost no risks or side effects for healthy candidates. However, there is the possibility of an allergic reaction to one or more of the ingredients within the topically applied serums used, which would become clear immediately on application by the appearance of redness.

Who Should Not be Treated with Electroporation Treatment?

Due to the electrical output of electroporation devices, treatment is not suitable for pregnant women or those people with epilepsy, pacemakers, or any serious psychological or medical condition. If you are healthy and don’t have any skin diseases or infections in the area treated, there are a few medical reasons why patients should not undergo this treatment.

DERMATOLOGISTS ONLY SKINCARE PRODUCTS RESULTS (BEFORE AND AFTER)

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