Laser-Assisted Drug Delivery

Laser-assisted drug delivery (LADD) is an emerging concept for a variety of aesthetic and therapeutic indications. With the growing popularity of laser and energy-based devices, aesthetic providers can adopt LADD to augment treatments with topical medication.

HOW DOES LADD WORK?

The absorption of topical medications into the skin is limited by the protective barrier of the stratum corneum, which on average limits absorption to 1% to 5% of the applied dose.^1,2 Lasers help to enhance transcutaneous absorption by causing microscopic breakdown of the skin barrier, which can be accomplished by both ablative fractional (AFL) and non-ablative fractional (NAFL) devices. These devices both create microscopic channels in the skin, which re-epithelize over time. As an added benefit, the use of one of these lasers alone may offer a therapeutic and beneficial effect. For instance, when LADD is used to deliver intralesional steroids for treatment of hypertrophic scars, the fractional laser therapy itself offers additional collagen breakdown and scar remodeling, which is not achieved with injection of steroids alone.¹

TREATMENT CONSIDERATIONS

When designing treatment regimens, the provider must consider the laser, patient, and drug/compound characteristics. While LADD can be performed with either AFL or NAFL devices, studies support the use of AFLs for the most benefit.³ Three laser parameters must also be chosen carefully based on treatment goals: fluence, density, and zone of coagulation. Laser fluence or energy determines the depth and width of the channels created in the skin—while drug penetration increases proportionally with channel depth, this effect plateaus around 500 µm to 700 µm, with increased depth yielding higher risk of adverse effects without increased therapeutic effect of the drug. Density reflects how many channels are created per treatment zone, with increased density correlating with increased penetration, though again plateauing at a density of about 5%. The zone of coagulation refers to the thin area of thermal injury surrounding each channel in the skin; while substances are absorbed at varying thicknesses depending on their hydrophilicity, a thin zone of coagulation (20 µm or less) is recommended for optimal absorption of most drugs. Patient skin characteristics, including Fitzpatrick skin type and anatomical site, should also guide treatment settings, with special care to avoid post-inflammatory hyperpigmentation in dark skin tones.

While drug properties, such as molecule size and vehicle, impact transcutaneous penetration with smaller, more hydrophobic molecules and liquid gel formulations yielding high absorption, timing of application is also crucial. Studies show increased absorption of the drug up to 6 hours post AFL treatment, with peak absorption occurring with 30 minutes of laser treatment, while the laser-induced channels in the skin are still intact.⁴

CLINICAL APPLICATIONS

The range of applications of LADD is a growing area of research. While LADD is being adopted for medical indications including treatment of skin cancers, the remainder of this article will focus on the cosmetic indications for this technology. The most common lasers studied in LADD are AFLs and, to a lesser degree, NAFLs.5 AFLs, namely the carbon dioxide (CO2) laser, have been cited to produce highly effective and reproducible results when combined with LADD.1 In one study, 10 individuals (FST I-III) with moderate-to-severe perioral rhytids underwent three bimonthly treatments with a low-density fractional CO2 laser followed by topical application of a poly-L-lactic acid (PLLA) suspension.6 PLLA is not only an injectable filler but also a biostimulator that has been shown to stimulate neocollagenesis.^3,6,7 Wrinkle severity before and after treatment was analyzed by computer-generated analyses, and after three treatments, wrinkle severity was decreased by an average of 47% (p < 0.05).6 A retrospective review performed over a 3.5-year period at a high-volume laser center found similar improvements in rhytids with AFL LADD performed with topical PLLA and supported the effectiveness in treating other etiologies, including atrophic surgical and traumatic scars, skin laxity, and fine lines.³ Over 3.5 years, 57 patients underwent a total of 71 treatments with the fractional ablative CO2 laser immediately followed by topical PLLA application. Using the Global Aesthetic Improvement Scale (GAIS), comparing pretreatment photographs to the patient’s follow-up visit photographs at a minimum of 4 weeks, the median improvement was graded as “much improved.”³ Notably, most of this patient cohort (80.7%) only underwent a single treatment and saw strong clinical improvement, which the authors attribute to synergistic interactions between the laser therapy and topically applied PLLA.³

Atrophic scars represent another difficult-to-treat indication for which LADD has shown promise. In a recent study, 19 patients received treatment with an ablative fractional CO2 laser, followed by topical application of PLLA.7 Eighteen of the 19 received only one treatment session, with one patient receiving two treatments. At their 3-month follow up, four dermatologists blinded to the study rated 95% of scars improved.7

Several other topical combinations have been shown to have augmented therapeutic effects with deeper penetration afforded through LADD. These include analgesics, medications used in photodynamic therapy such as aminolaevulinic acid, topical antioxidants, imiquimod, 5-fluorouracil, corticosteroid, and others.^2,6 With further studies, there is evidence in favor of the potential clinical applications of LADD to include several other common dermatotic conditions such as scars, warts, dyspigmentation, alopecia areata, skin cancer, and melasma.

IMPORTANT CONSIDERATIONS

As with any treatments, there is always the potential for adverse effects. As previously mentioned, increased channel depth, laser densities, and coagulation zones may affect the efficacy and safety of LADD.^5,8 Balance must be achieved between the correct treatment settings for improved topical penetration, while mitigating the risk of burns and/or scars. It is important for the topicals being applied to be well-studied in terms of their ingredients and components to avoid potential foreign body or hypersensitivity reactions. Local cutaneous reactions are also a potential risk that must be accounted for. For example, intensified local cutaneous responses after AFL-assisted photodynamic therapy (PDT) have been shown in contrast to PDT alone.⁵ It is therefore important to be well-aware of local and systemic reactions to topically applied medications and the potential for these effects to present with prominence through LADD. In addition to patient skin type, which should be considered when using any laser, the patient anatomic site is also important as the thickness of the dermis, as well as the presence of adnexal structures, will impact the degree of penetration of substances. Transfollicular penetration can increase the absorption of medications, thereby potentially increasing the effect of topicals absorbed.5 Given the complexity and various considerations that must be taken into account, it is imperative that individuals seek LADD providers with an in-depth understanding of the skin, in addition to laser science and treatment.

CONCLUSION

Laser-assisted drug delivery is emerging in popularity as an approach to treat a wide variety of medical and aesthetic dermatologic indications. Through inducing a zone of thermal damage, lasers help to achieve a higher penetration of topically applied medications, improving their absorption and biologic effects. In-depth training in technique along with fundamental knowledge of the skin, laser, and topical medication properties is critical to allow treatments to be performed safely and effectively.

1. Labadie JG, Ibrahim O, and Dover JS. Laser-Assisted Drug Delivery. Advances in Cosmetic Surgery. 2023;6(1):19-30.

2. Labadie JG, et al. Evidence-Based Clinical Practice Guidelines for Laser-Assisted Drug Delivery. JAMA Dermatol. 2022;158(10):1193-201.

3. Steuer AB, Bajaj S, Wang JV, and Geronemus RG. Safety and Effectiveness of Fractional Ablative CO 2 Laser-Assisted Delivery of Topical Poly- l -Lactic Acid for Rhytides and Scars. Dermatol Surg. 2024;50(4):400-02.

4. Banzhaf CA, et al. Fractional laser-assisted drug uptake: Impact of time-related topical application to achieve enhanced delivery. Lasers Surg Med. 2017;49(4):348-54.

5. Ibrahim O, et al. Challenges to laser-assisted drug delivery: Applying theory to clinical practice. Lasers Surg Med. 2018;50(1):20-27.

6. Ibrahim O, et al. Safety of Laser-Assisted Delivery of Topical Poly-L-Lactic Acid in the Treatment of Upper Lip Rhytides: A Prospective, Rater-Blinded Study. Dermatol Surg. 2019;45(7):968-74.

7. Rkein A, Ozog D, Waibel JS. Treatment of atrophic scars with fractionated CO2 laser facilitating delivery of topically applied poly-L-lactic acid. Dermatol Surg. 2014;40(6):624-31.

8. Sklar LR, Burnett CT, Waibel JS, Moy RL, Ozog DM. Laser assisted drug delivery: a review of an evolving technology. Lasers Surg Med. 2014;46(4):249-62.