Towards the enhancement of transdermal drug delivery through thermocavitation

Abstract

AbstractAlthough for some highly lipophillic drugs the principal barrier to permeate the human skin may reside in the essentially viable epidermal membrane, for most molecules, the stratum corneum (SC) is the rate-limiting barrier to drug delivery. Today, several techniques have been developed to enhance transdermal drug delivery (TDD) by increasing the effective permeability of the SC (e.g., iontophoresis, electroporation, micro-needle, ultrasound, radio frequency and laser radiation). The goal of this study is to investigate the extent to which thermocavitation may be used as a novel alternative method to selectively pierce the SC and thus enhance TDD. Thermocavitation for this purpose is generated by a continuous wave (CW), low power laser beam focused on a highly-absorbing solution topically applied on the skin surface. The absorbed light creates a superheated volume in a tightly localized region followed by explosive phase transition and the formation of vapor-gas bubbles, which expand and later collapse very rapidly emitting intense acoustic shockwaves that disrupt the surface underneath.Thermocavitation bubbles were induced close to the surface of skin models (agar gels) andThe damage observed on agar gel and porcine skin appears to be congruent with the relationship between laser power, focal point, cavitation frequency and extent of damage observed in previous studies. In particular, the greatest damage induced to the agar phantoms was produced with the lowest laser power (∼153 mW) and thinnest solution layer (∼100 μm) used. Similar laser and solution layer settings led to porcine skin damage of ∼80–100 μm in diameter, which was sufficiently large to break the SC and allow the penetration of 4 kDa, FITC-dextran to depths of ∼40–60 μm.This novel approach to achieve cavitation is attractive and seems promising because it can be generated with inexpensive, low power CW lasers, capable of selectively disrupting the SC and allowing the penetration of large, hydrophilic drugs topically applied to the skin.