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Towards the enhancement of transdermal drug delivery through thermocavitation
JUAN PABLO PADILLA MARTINEZ
JULIO CESAR RAMIREZ SAN JUAN
RUBEN RAMOS GARCIA
Acceso Abierto
Atribución-NoComercial-SinDerivadas
Thermocavitation
Stratum corneum
Tape stripping
H&E technique
Drug delivery
Background and objective: Although 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 volumen 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. Materials and methods: Thermocavitation bubbles were induced close to the surface of skin models (agar gels) and ex-vivo porcine skin samples using a 975 nm CW laser, focused on a thin (100 – 300 μm) topical layer of copper nitrate (CuNO₄ ). The damage induced by thermocavitation on the surface of agar tissue phantoms was analyzed by optical microscopy and the penetration depth of a fluorescent drug surrogate (FITC dextran, molecular weight=4 kDa), applied topically to the surface of ex-vivo porcine skin samples following thermocavitation. The corresponding histological structure was analyzed by fluorescent microscopy and hematoxylin and eosin (H&E) staining, respectively. Results: The 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.
Photonics and Lasers in Medicine
2012
Artículo
Inglés
Estudiantes
Investigadores
Público en general
Padilla Martínez, J. P., et al., (2012), Towards the enhancement of transdermal drug delivery through thermocavitation, Photonics and Lasers in Medicine, Vol. 1(3):183–193
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