In response to increasing patient interest in regenerative medicine for healthy and youthful skin, the industry has responded with technologies and devices that promote skin permeability for effective delivery of topicals, including regenerative ingredients such as exosomes, growth factors, peptides and more. Known as intradermal or transdermal delivery devices, these technologies enhance transepidermal delivery of specific topicals in a minimally invasive manner to stimulate and support tissue and cell regeneration for enhanced outcomes.
The Evolution of Intradermal Delivery Technologies
While transdermal patches are often what comes to mind for intradermal delivery, electroporation, which uses electrical pulses to create temporary pores, is also beginning to draw attention. For now, however, the greatest focus remains on energy- and microneedlingbased options for topical drug delivery.
Microneedling, or collagen induction therapy, is a popular method for transdermal delivery of active products in aesthetics. Board-certified dermatologist Todd Schlesinger, MD, director for the Clinical Research Center of the Carolinas (Charleston, S.C.), has used this treatment in his practice for the last decade. “Micronee
dling started with simple rolling devices and evolved into powered pens,” he reported. “We now have energy-based devices that combine microneedling with radiofrequency (RF) energy as one of our primary modalities in the management of aging skin and other conditions such as acne scarring.
“I primarily employ microneedling to aid in the penetration of topical cosmetics, such as growth factors, collagen stimulators and peptides,” Dr. Schlesinger continued. “Exosomes derived from various sources are more commonly employed today. We often apply 5-fluorouracil (5-FU) topically after microneedling or laser, both ablative and non-ablative, to treat hypertrophic, keloid and post-surgical scars. Some providers use similar techniques to help the penetration of aminolaevulinic acid prior to photodynamic therapy.”
According to Dr. Schlesinger, laser-assisted drug delivery (LADD) is another option that specifically aids in penetration of poly-L-lactic acid (PLLA), neuromodulators or mixtures of various types of hyaluronic acid (HA) to improve the skin. “We use lasers differently for penetration enhancement,” he explained. “We can limit the depth of laser penetration to the epidermis to avoid irritation and sensitization and penetrate the stratum corneum without placing too much product into the dermis.”
Recent research is mixed on ideal delivery methods. One 2023 study1 indicated that fractional CO2 lasers provided superior results in transdermal drug delivery compared to microneedle-facilitated delivery. Another review2 found that RF microneedling (RFMN) may be as effective as a CO2 laser for acne scar remodeling, with RFMN offering a non-invasive approach and more appropriate for darker skin tones.
Michael Gold, MD, founder and medical director of Gold Skin Care Center, Advanced Aesthetics Medical Spa, The Laser & Rejuvenation Center, and Tennessee Clinical Research Center (Nashville, Tenn.), employs both microneedling and a CO2 fractional laser to promote deep 
absorption of topicals. “I use sterile triamcinolone acetonide following CO2 fractional laser therapy for the treatment of hypertrophic scars and keloids. The fractional CO2 laser goes deep within the scar to open channels and then I apply the sterile triamcinolone acetonide to the treated area immediately after the procedure. We may recommend patients return every six to eight weeks, if needed. We also treat hypertrophic scars and keloids with corticosteroids post-needling to help reduce these scars.”
Dr. Gold shared that his favorite technique is RFMN plus exosomes for hair loss. “Microneedling establishes channels for the topical applications of the exosomes to penetrate into the dermis and allow them to exert their effects on the hair follicles. I mainly use non-insulated needles for this treatment, which is performed at monthly intervals with typically three to four treatments for this form of therapy.”
There has been an escalation in the use of exosomes in the past several years, according to Dr. Gold who offered a note of caution. “Exosomes show very promising data. We are seeing positive effects with intradermal drug delivery and beginning to see the clinical work to support their effectiveness in aesthetic medicine. However, clinicians should ask what clinical work is being done with whichever exosome company they are using. Make sure that they are an established company and not just a fly-by-night company trying to capitalize on a ‘hot’ topic.”
Although research on exosomes and transdermal devices is limited, there are a few early studies that show promise. In one study,3 researchers applied rose (Rosa damascena) stem cell exosomes after microneedling in participants with Fitzpatrick skin types I-III. Of these, 90% showed significant improvement with favorable tolerability and only mild, transient side effects, warranting further research. Exosome-based molecules are also being investigated as a new-generation vehicle for drug delivery of biomedical applications.4
Erez Dayan, MD, a plastic surgeon and owner of Avance Plastic Surgery Institute (Reno, Nev.), emphasized that microneedling is a cornerstone in most aesthetic practices today thanks to the advancement of treatments like platelet-rich plasma (PRP) and exosomes. “One of our most common treatments that utilize transdermal drug delivery includes microneedling with PRP for anti-aging purposes,” he reported. “The use of PRP and tranexamic acid and exosomes have proven to be safe and effective, and we find that PRP helps patients recover more quickly from the redness after microneedling and improves the overall results. We also use microneedling and PRP for hair stimulation and tranexamic acid over microneedling for patients with dark undereye circles.”
DiAnne Davis, MD, a board-certified and fellowship-trained dermatologist in Dallas, Texas, also combines microneedling with topical tranexamic acid or PRP tailored for her patient demographic in her practice. “I use microneedling to drive the tranexamic acid deeper into the skin to help even out the skin tone and PRP to further enhance the results o
f the microneedling procedure and reduce downtime.”
Dr. Davis incorporates CO2 or Er:YAG lasers to treat surgical, hypertrophic and keloid scars by delivering drugs such as triamcinolone acetonide to help to break down the collagen fibers and reduce the amount of scar tissue, or 5-FU to inhibit the cellular proliferation that leads to the development of scars. “For scars that are hypopigmented, I combine LADD with bimatoprost to help restimulate pigment,” she added.
While she is not aware of any topicals that have been created specifically for LADD, Dr. Davis explained that the dermatology literature lists a host of medications including methotrexate, betamethasone, minoxidil and onabotulinum toxin that have been delivered via laser for a number of dermatologic conditions. “Certain cosmeceuticals, such as antioxidants, salicylic acid, ascorbic acid and hydroquinone have also been utilized with LADD. We are now also starting to see biostimulatory agents such as PLLA utilized for the improvement of depressed or atrophic scars, skin texture and fine lines and wrinkles.”
What’s Next for Intradermal Technology?
As research evolves, so too will device and product technologies. “Several studies have shown that topically applying the drug or ingredient before treatment with a microneedling device allows for deeper penetration,” Dr. Davis shared. “But this will also depend on various qualities of the topical used such as molecular weight, potential of hydrogen (pH) and lipophilicity.”
One innovative device allows Dr. Davis more control over the topical she applies. “I utilize fractionated Er:YAG and fractionated 1064 nm Nd:YAG laser devices for the treatment of scars, hyperpigmentation or melasma. To apply the topical agent, I will often use a 1 mL or 3 mL syringe to gently drip the product onto the skin. At my current practice we have the CuraCator™ device from Air-Tite Aesthetics (Virginia Beach, Va.), which is a non-sharp device that attaches to the end of a Luer Lock syringe, allowing for an even spread of fluid that is dispersed through the tip of the device. It helps to accurately control how topical products are dispensed and dispersed on top of the skin.”
Hollow needles are another technology update on the horizon, Dr. Dayan noted. “The current method of spreading medication over microneedling channels is less precise and it is difficult to quantify how much medication is reaching the channels and depth,” he reported. “I am familiar with RF device companies looking into hollow needles that intend to d
eliver drugs subdermally in higher quantities with more precision. The use of standard microneedling creates small channels for drug delivery; however, this new system of using hollow needles may allow for more efficient drug delivery.” He added that there are also devices in development that will have the ability to preferentially deposit drugs at different depths.
Despite the excitement of what the future holds for transdermal devices, Dr. Schlesinger feels providers should continue to do their due diligence, including knowing the patients’ background and the ingredients of any topical skincare technology before application. “The skin is a barrier with complex immune functionality. Penetrating it with certain products like retinoids or topical vitamin C that are not designed for injection may lead to irritation or a potentially long-term problem,” he clarified.
Product Watch List
Adding even more functionality to their Morpheus* RF microneedling device, InMode (Irvine, Calif.) introduces Morpheus8 Burst and Burst Deep devices with innovative SCALE and Burst functionalities to offer a comprehensive approach to transdermal topical delivery. These proprietary technologies automatically deploy bipolar RF to multi-level treatment depths and programmable energy levels in millisecond internals with a single pulse. Morpheus8 Burst is designed to safely and efficaciously meet patient demand for dermal 
contraction and subdermal adipose treatments. Morpheus8 Burst Deep provides the deepest available levels of targeted RF energy deposition, protecting dermal pigment while allowing greater energy to be deployed to the Fibro Septal Network (FSN) and adipose tissue.
Glowpin™ by PDO Max® (Liverpool, N.Y.) is a multi-needle stamping device specifically designed for the application of topical skin boosters, allowing them to flow easily, effectively and with optimal absorption. The nineteen 32G hypodermic surgical steel needles ensure accurate penetration and direct delivery of serums, while the airless press pump allows for controlled application and diffusion of the serum.
Each needle is equally positioned for equal diffusion with a penetration depth of 0.5 mm at a 90° angle and the lancet 2x cut needle technology helps reduce pain and the risk of injury. The GlowPin was designed with PDO Max’s AfterGlo® serum in mind but can be used with most topicals including PRP and exosomes.
Scarlet SRF from Aesthetic Management Partners (Cordova, Tenn.) is an RFMN system that employs a patented single-pulse microneedling technology to deliver RF energy through 25 noninsulated microneedles that penetrate from 0.5 mm to 3.5 mm, creating controlled, fractionated micro-injuries in the skin, enabling effective intradermal penetration of topical treatments. This unique design incorpor
ates an individual electrode around every microneedle in a distinctive arrangement that forms a teardrop-shaped micro-injury to effectively engage the entire dermal layer of the skin. A smooth-running and consistent robotic motor delivers the gold-plated microneedles in a gently controlled motion, providing a well-tolerated patient experience without compromising the speed of treatment. Well-documented, positive clinical results coupled with minimal downtime and discomfort firmly place Scarlet SRF into the realm of superior aesthetic devices.
The Collagen P.I.N.® Microneedling System from Induction Therapies (Louisville, Ky.) significantly enhances the delivery of post-skincare topicals by leveraging advanced 36-pin needle technology to deliver more uniform microneedling results, less patient downtime and a heightened return on investments for aesthetic providers. By creating precise microchannels in the skin for topical delivery, treatments with Collagen P.I.N. initiate and enhance the natural healing response to boost collagen and elastin production. The microchannels serve as direct pathways for skincare products to penetrate into deeper layers of the skin, thereby increasing their efficacy. With Co
llagen P.I.N., active ingredients, such as plant-derived exosomes found in PRX⁸ Plant- Exo System by Induction Therapies, can be absorbed more effectively and work more efficiently at the cellular level to expedite results and further reduce patient downtime.
PRX Derm Perfexion from WiQo® (Muggia, Italy) is a non-invasive Topical Collagen Biostimulator™ clinically proven to help tighten, tone and lift the skin for visible rejuvenation of the face and body delivering the ultimate PRX GLOW™. Invented by the founder of WiQo, Rossana Castellana, MD, PRX is a globally pantented professional treatment formulated with 33% trichloroacetic acid (TCA) and hydrogen peroxide that is clinically proven to deliver immediate and long-lasting results with no needles, no discomfort and no downtime. PRX can be combined with microneedling and RF microneedling for intradermal penetration.
References:
1. Indramaya DM, Listiawan MY, Citrashanty I, et al. The Comparison between Microneedling and Fractional CO2 Laser for Amniotic Membrane Stem Cell-Conditioned Medium and Vitamin C in Photoaging Treatment. Indian J Dermatol. 2023;68(4):430-436. doi:10.4103/ijd.ijd_839_20
2. Meghe S, Saoji V, Madke B, Singh A. Efficacy of Microneedling and CO2 Laser for Acne Scar Remodelling: A Comprehensive Review. Cureus. 2024;16(2):e55092. Published 2024 Feb 27. doi:10.7759/cureus.55092
3. Proietti I, Battilotti C, Svara F, Innocenzi C, Spagnoli A, Potenza C. Efficacy and Tolerability of a Microneedling Device plus Exosomes for Treating melasma. Preprints. 2024. https://doi.org/10.20944/preprints202402.1458.v1
4. Rajput A, Varshney A, Bajaj R, Pokharkar V. Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives. Molecules. 2022;27(21):7289. Published 2022 Oct 27. doi:10.3390/ molecules27217289
