Fractional Ablative Laser Followed by Transdermal Acoustic Pressure Wave Device to Enhance the Drug Delivery of Aminolevulinic Acid: In Vivo Fluorescence Microscopy Study

January 2016 | Volume 15 | Issue 1 | Original Article | 14 | Copyright © 2016

Jill S. Waibel MD,a Ashley Rudnick,a Carlos Nousari MD,b and Dhaval G. Bhanusali MDc

aMiami Dermatology and Laser Institute, Miami, FL
bDermpath Diagnostics, Pompano Beach, FL
cSadick Dermatology /Weill Cornell Medical College, New York, NY

Abstract

BACKGROUND: Topical drug delivery is the foundation of all dermatological therapy. Laser-assisted drug delivery (LAD) using fractional ablative laser is an evolving modality that may allow for a greater precise depth of penetration by existing topical medications, as well as more efficient transcutaneous delivery of large drug molecules. Additional studies need to be performed using energy-driven methods that may enhance drug delivery in a synergistic manner. Processes such as iontophoresis, electroporation, sonophoresis, and the use of photomechanical waves aid in penetration. This study evaluated in vivo if there is increased efficacy of fractional CO2 ablative laser with immediate acoustic pressure wave device.
METHODS: Five patients were treated and biopsied at 4 treatment sites: 1) topically applied aminolevulinic acid (ALA) alone; 2) fractional ablative CO2 laser and topical ALA alone; 3) fractional ablative CO2 laser and transdermal acoustic pressure wave device delivery system; and 4) topical ALA with transdermal delivery system. The comparison of the difference in the magnitude of diffusion with both lateral spread of ALA and depth diffusion of ALA was measured by fluorescence microscopy.
RESULTS: For fractional ablative CO2 laser, ALA, and transdermal acoustic pressure wave device, the protoporphyrin IX lateral fluorescence was 0.024 mm on average vs 0.0084 mm for fractional ablative CO2 laser and ALA alone. The diffusion for the acoustic pressure wave device was an order of magnitude greater.
CONCLUSION: We found that our combined approach of fractional ablative CO2 laser paired with the transdermal acoustic pressure wave device increased the depth of penetration of ALA.

J Drugs Dermatol. 2016;15(1):14-21.

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INTRODUCTION

Laser-Assisted Drug Delivery

Topical drug delivery is the foundation of all dermatological therapy. However, therapeutic benefit is often ultimately limited by absorption of the medication. The stratum corneum (SC), the outermost layer of the skin, serves as the rate-limiting step for percutaneous penetration. Because of this barrier, only 1% to 5% of topically applied drugs absorb into the skin.1 Furthermore, many medications are too large to penetrate and require either an injectable or systemic delivery.

Laser-assisted drug delivery (LAD) is an evolving modality that may allow for a greater precision of depth penetration by existing topical medications, as well as a more efficient transcutaneous delivery of drug molecules.2 High energy fractional laser therapy is a unique ablative modality that has the ability to destroy the SC, epidermal, and dermal layers in a predictable and controlled pattern, resulting in the potential for increased penetration of topically applied molecules.

Laser-assisted drug delivery is an emerging modality that provides a novel way to overcome issues faced by traditional therapy.3 It provides a greater and more precise depth of penetration than existing topical medications, more efficient transcutaneous delivery of large drug molecules, and potentially a way of delivering systemic medication via a transcutaneous route.2 Ablative fractional resurfacing is a new treatment model that creates vertical channels of ablation surrounded by thin layers of coagulated tissue known as microthermal zones (MTZ).3 The creation of these channels theoretically serve as access points for drug delivery and allow for transport of actives deeper into the skin than would otherwise be possible.

As LAD is a new field, we need to optimize strategies for cutaneous delivery of drugs and molecules. Our goals for a cutaneous delivery system would include increasing the efficacy of the drug at target tissue, decreasing toxicity to other organs (gastrointestinal tract), decreasing the amount of drug needed

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