Fractional Laser-assisted Drug Delivery Research Articles

49921 Safety of Ablative Fractional Laser-Assisted Drug Delivery

49921 Safety of Ablative Fractional Laser-Assisted Drug Delivery

The role of fractional laser-assisted drug delivery in enhancing the efficacy of topical bimatoprost solution in the treatment of alopecia areata: An intra-patient comparative randomized clinical trial.

Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. This is a prospective intra-patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. SALT score was reduced significantly during treatment sessions and after a 3-month follow-up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow-up period, respectively (p = 0.000). A general linear model of two-way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata.

The Role of Fractional CO2 and Pulsed Dye Laser in Scar Management

Introduction: An estimated 100 million patients acquire scars of any type every year, a few of which will lead to hypertrophic, contracting scars or keloids. Management remains challenging and encompasses surgical and non-surgical treatment options. The introduction of fractional photothermolysis (FP) in 2004,marked a major advancement in treatment. Unlike classic non-fractional ablative lasers, FP uses well focused laser beams to create small columns of ablation called microscopic treatment zones (MTZ).FP has since been discovered to be particularly useful in relieving scar contractures with efficacy on improving functionality and cosmetic outcomes. We aim to present a case of a contracting scald burn over the buttocks improving exceptionally following pulsed dye (595 nm) laser and fractional resurfacing using an ablative CO2 (10600 nm) laser associated with transepidermal triamcinolone delivery. Materials and Methods: Case presentation of the management of a hypertrophic scar following a scald burn. Results: A 12 year old boy suffered a third degree scald burn on the right buttock requiring a split thickness skin graft. The follow-up was complicated by a contracting, hypertrophic scar with a negative impact on his soccer playing due to diminished running ability. we started treatment with pulsed dye laser (595 nm, handpiece of 12 mm, pulse duration of 6 ms, fluence of 5 à 6 J/cm2),fractional resurfacing treatments using an ablative fractional CO2 laser(10600 nm, Deep-Fx, 30 to 50 mJ/MTZ, 5% coverage)followed by topical triamcinolone application by the principle of fractional laser-assisted drug delivery. We applied a hydrocolloid dressing 24/7,wearing compression shorts and to massage the scar regularly. After a total of 19 treatments, we observed a smooth scar without any signs of contraction and a normal range of motion of the hip joint. The patient was highly satisfied with the functional and aesthetic result. Conclusion: Lasers are a safe and effective treatment option for traumatic scars. Choosing the appropriate laser with the appropriate dosimetry is one of the cornerstones to a good scar-management.

Comparison of fractional laser-assisted drug delivery and intralesional injection of triamcinolone acetonide in nail psoriasis.

The treatment of nail psoriasis is often unsatisfactory due to poor penetration of topical therapeutics through the nail plate. The development of innovative methods that provide adequate delivery of the drug into the nail is warranted. In this study, we aim to compare the efficacy of intralesional corticosteroid injection versus its topical application after fractional CO2 laser in the treatment of fingernail psoriasis. The study included 36 patients with fingernail psoriasis divided into two groups. The nails in group A were treated with intralesional injection of triamcinolone acetonide while the nails in group B received fractional CO2 laser therapy followed by topical application of the drug for six sessions. The evaluation was performed using NAPSI and dermatoscopic scores. Both modalities yielded a significant improvement of the nail matrix and bed psoriatic signs. No statistically significant difference was found between the two groups by both clinical and dermatoscopic assessment. The laser treatment was associated with significantly lower pain scores (P=0.03) and higher patient satisfaction (P=0.007). Fractional CO2 laser-assisted delivery of topical corticosteroids can be a potentially effective and well-tolerated therapeutic modality in the treatment of nail psoriasis with comparable efficacy to intralesional injection.

A simple, inexpensive, and reproducible wound dressing to optimize topical drug absorption after ablative fractional laser-assisted drug delivery

Laser-assisted drug delivery uses an ablative fractional laser to create microchannels in skin to overcome the epidermal barrier and improve drug delivery to the intended target while providing therapeutic benefit from the laser itself.1 There are no standard protocols regarding postprocedural care and, in particular, how to optimize penetration of topical agents before laser microchannels re-epithelialize, which occurs approximately 48 hours after laser treatment. In accordance with our experience treating burn scars with topical triamcinolone acetonide, we describe a simple, affordable, and readily adoptable dressing to optimize drug delivery for select topical agents while laser microchannels are still patent.

Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation

Oral administration of vismodegib for basal cell carcinoma treatment is limited by significant class-specific systemic side effects. We investigated the approach of combining ablative fractional laser-assisted drug delivery with an extended-release microemulsion formulation of vismodegib to provide efficient cutaneous delivery invivo. The developed formulation consisted of an oil-in-water microemulsion stabilized by Tween-80. Pig skin was exposed to ablative fractional laser followed by topical application of vismodegib microemulsion for 4 hours. At 4 hours, 2 days, 5 days, and 9 days, we evaluated vismodegib biodistribution in superficial, mid, and deep dermis and plasma (n= 189 measurements) and assessed local skin reactions. Sustained topical delivery of vismodegib was detected in all depths of ablative fractional laser-exposed skin over the course of the study, with peak concentrations found at 5 days and 9 days. The highest vismodegib concentrations reached 1,409.7 μmol/liter in superficial dermis and 62.3 μmol/liter in deep dermis, exceeding steady-state plasma concentrations previously reported for oral administration of vismodegib (5.5-56.0 μmol/liter). Ablative fractional laser increased vismodegib uptake up to 16.6-fold compared with intact skin. Only mild local skin responses to vismodegib were observed, and no vismodegib was detected in plasma. We report sustained topical delivery of vismodegib invivo at high concentrations with favorable skin tolerability, suggesting a future safer vismodegib treatment.

Opportunities for laser-assisted drug delivery in the treatment of cutaneous disorders.

Fractional laser-assisted drug delivery (LADD) is increasingly finding its way into clinical practice as a new means to enhance topical drug uptake and improve treatment of cutaneous disorders. To date, LADD has been used for a wide range of conditions, including photodamaged skin, neoplastic lesions, scars, cutaneous infections, and vitiligo as well as for topical anesthetic and aesthetic procedures. Substantiated by randomized controlled clinical trials, strong evidence is available for LADD's usefulness for photodynamic therapy (PDT), for which improved efficacy using laser-assisted photosensitizer treatment is established for actinic keratosis compared with conventional PDT. Over time, the modality has undergone increasing refinement and offers the potential advantages of reduced treatment durations, shortened incubation times, and the replacement of cumbersome, patient-dependent treatment regimens with quick, in-office procedures. Notwithstanding, LADD is still a new enhancement technique, and risks of both local and systemic adverse events are insufficiently explored. With conscientious development, however, LADD promises to improve existing regimens and make new pharmacological treatments a reality for a wide range of cutaneous disorders.

Fractional laser-assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration.

Ablative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug-induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser-generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous deposition and delivery kinetics; (iii) biodistribution and diffusion pattern, estimated by mathematical simulation. Franz diffusion chambers (FCs) were used to evaluate the PVP-technique, comparing passive (AFXL) and active (AFXL + PVP) channel filling. A fractional CO2-laser generated superficial (225 µm;17.5 mJ/channel) and deep (1200 µm; 130.5 mJ/channel) channels, and PVP was delivered as a 3-minutes cycle of 1 minute pressure (+1.0 atm), 1 minute vacuum (-1.0 atm), and 1 minute pressure (+1.0 atm). Filling of laser channels was visualized with a colored biomarker liquid (n = 12 FCs, n = 588 channels). Nuclear magnetic resonance quantified intracutaneous deposition of topically applied polyethylene glycol (PEG400) over time (10 minutes, 1 hour, and 4 hours), investigated with (n = 36 FCs) and without (n = 30 FCs) PVP-filling. Two-dimensional mathematical simulation was used to simulate intradermal biodistribution and diffusion at a depth of 1,000 µm. Active filling with application of PVP increased the number of filled laser channels. At a depth of 1,000 µm, filling increased from 44% (AFXL) to 94% with one PVP cycle (AFXL + PVP; P < 0.01). Active filling greatly enhanced intracutaneous deposition of PEG400, resulting in a rapid delivery six-folding uptake at 10 minutes (AFXL 54 µg/ml vs. AFXL + PVP 303 µg/ml, P < 0.01). AFXL alone generated an inhomogeneous uptake of PEG400, which greatly improved with active filling, resulting in a uniform uptake within the entire tissue. Active filling with PVP secures filling of laser channels and induces a deeper, greater, more rapid delivery than conventional AFXL. This delivery technique has promise to improve treatment efficacy for medical treatments of dermally invasive lesions, such as BCCs.

Feasibility of ablative fractional laser-assisted drug delivery with optical coherence tomography.

Fractional resurfacing creates hundreds of microscopic wounds in the skin without injuring surrounding tissue. This technique allows rapid wound healing owing to small injury regions, and has been proven as an effective method for repairing photodamaged skin. Recently, ablative fractional laser (AFL) treatment has been demonstrated to facilitate topical drug delivery into skin. However, induced fractional photothermolysis depends on several parameters, such as incident angle, exposure energy, and spot size of the fractional laser. In this study, we used fractional CO2 laser to induce microscopic ablation array on the nail for facilitating drug delivery through the nail. To ensure proper energy delivery without damaging tissue structures beneath the nail plate, optical coherence tomography (OCT) was implemented for quantitative evaluation of induced microscopic ablation zone (MAZ). Moreover, to further study the feasibility of drug delivery, normal saline was dripped on the exposure area of fingernail and the speckle variance in OCT signal was used to observe water diffusion through the ablative channels into the nail plate. In conclusion, this study establishes OCT as an effective tool for the investigation of fractional photothermolysis and water/drug delivery through microscopic ablation channels after nail fractional laser treatment.

Histologic comparison of microscopic treatment zones induced by fractional lasers and radiofrequency

Introduction: Fractional photothermolysis induces microscopic, localized thermal injury in the skin surrounded by undamaged viable tissue in order to promote wound healing. Objective: This study evaluated acute histologic changes following each single pass of various fractional lasers and radiofrequency (RF). Methods: Three male domestic swine were used. We used fractional Erbium:glass (Er:glass), Erbium:yttrium-aluminum-garnet (Er:YAG), CO2 lasers, and fractional ablative microplasma RF. We analyzed features and average values of the diameter, depth, and vertical sectional areas treated with each kind of laser and RF. Results: The microscopic treatment zone (MTZ) of fractional Er:glass resulted in separation of dermoepidermal junction with no ablative zone. Fractional Er:YAG provided the most superficial and broad MTZ with little thermal collateral damage. Fractional CO2 resulted in a narrow and deep “cone”-like MTZ. Fractional RF resulted in a superficial and broad “crater”-like MTZ. Conclusions: This study provides the first comparison of MTZs induced by various fractional lasers and RF. These data provide basic information on proper laser and RF options. We think that these findings could be a good reference for information about fractional laser-assisted drug delivery.

Fractional Carbon Dioxide Laser–Assisted Drug Delivery of Topical Timolol Solution for the Treatment of Deep Infantile Hemangioma: A Pilot Study

Infantile hemangiomas (IHs) are benign vascular tumors of infancy. Topical timolol has recently been reported to be an effective treatment for superficial IHs, although it failed to have an effect on deep IHs. This prospective study was aimed at evaluating the feasibility of ablative fractional laser-assisted drug delivery for enhancing topical timolol permeation into deep IHs. Nine patients ages 1 to 6 months with deep IHs were enrolled. A fractional carbon dioxide (CO2 ) laser system was applied to the skin surface of deep IHs using the DeepFx mode (25-30 mJ/pulse, 5% density, single pulse) at 1-week intervals. Topical timolol maleate 0.5% ophthalmic solution was applied under occlusion for 30 minutes four to five times per day for an average treatment duration of 14.2 weeks. Clinical improvement was evaluated according to a global score and the Hemangioma Activity Score (HAS). Four patients (44.4%) demonstrated excellent regression, four (44.4%) showed good response, and one (11.1%) experienced moderate regression. The HAS declined from 4.1 ± 0.7 at baseline to 1.7 ± 0.7 at 1 week (p < 0.001) and 1.4 ± 0.7 at 3 months (p = 0.03) after the last treatment procedure. Plasma timolol concentration was not detected in any of the patients after the first administration of topical timolol. No systemic complication or skin side effects were observed in any of the patients. Ablative fractional laser-assisted transdermal delivery of topical timolol is a safe and effective method for the treatment of deep IHs.

The impact of treatment density and molecular weight for fractional laser-assisted drug delivery

Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by creating narrow open micro-channels into the skin, but there is limited information on optimal laser settings for delivery of specific molecules. The objective of this study was to investigate the impact of laser treatment density (% of skin occupied by channels) and molecular weight (MW) for fractional CO2 laser-assisted drug delivery. AFXL substantially increased intra- and transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to 4300Da (Nuclear Magnetic Resonance, p<0.01). Increasing laser density from 1 to 20% resulted in augmented intra- and transdermal delivery (p<0.01), but densities higher than 1% resulted in reduced delivery per channel. Mass spectrometry indicated that larger molecules have greater intracutaneous retention than transcutaneous penetration. At 5% density, median delivery of PEGs with mean MW of 400, 1000, 2050 and 3350Da were respectively 0.87, 0.31, 0.23 and 0.15mg intracutaneously and 0.72, 0.20. 0.08 and 0.03mg transcutaneously, giving a 5.8- and 24.0-fold higher intra- and transcutaneous delivery of PEG400 than PEG3350 (p<0.01). This study substantiates that fractional CO2 laser treatment allows uptake of small and large molecules into and through human skin, and that laser density can be varied to optimize intracutaneous or transcutaneous delivery.