Fractional Laser-Assisted Drug Delivery: Active Filling of Laser Channels With Pressure and Vacuum Alteration

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Abstract

Background and Objective:

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.

Methods:

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.

Results:

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.

Conclusion:

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. Lasers Surg. Med. 48:116–124, 2016. © 2015 Wiley Periodicals, Inc.

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