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Abstract

In order to improve the therapeutic index of adapalene, a new drug under development for the treatment of acne, site-specific delivery to the hair follicles using 50:50 poly(DL-lactic-co-glycolic acid) microspheres as particulate carriers was investigated in vitro and in vivo. The percutaneous penetration pathway of the microspheres was shown to be dependent on their mean diameter. Thus, after topical application onto hairless rat or human skin, adapalene-loaded microspheres (5-microns diameter) were specifically targeted to the follicular ducts and did not penetrate via the stratum corneum. The in vitro release of adapalene from the microspheres into artificial sebum at 37 degrees C was controlled and faster than the in vivo sebum excretion in humans. Aiming to reduce either the applied dose of drug or the frequency of administration, different formulations of adapalene-loaded microspheres were evaluated in vivo in the rhino mouse model. A dose-related comedolytic activity of topical formulations of adapalene-loaded microspheres was observed in this model. Furthermore, by applying a site-specific drug delivery system (0.1% adapalene) every other day or by administering a 10-fold less concentrated targeted formulation (0.01%) every day, a pharmacological activity equivalent to a daily application of an aqueous gel containing drug crystals (0.1% adapalene) was observed. Since an aqueous gel containing 10% adapalene-loaded microspheres was not irritating in a rabbit skin irritancy test, this formulation was applied onto forearms of human volunteers. Site-specific drug delivery was further evidenced by follicular biopsy. Since an aqueous gel containing 10% adapalene-loaded microspheres was not irritating in a rabbit skin irritancy test, this formulation was applied onto forearms of human volunteers. Site-specific drug delivery was further evidenced by follicular biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Colloidal stability and in vitro permeation study of poly(ɛ-caprolactone) nanocapsules containing hinokitiol

“…On the other hand, despite of much bigger size, poly(D,L-lactic-co-glycolic acid) (PLGA) microparticles of several microns were found even in the upper epidermis, 24 h after applying them a porcine skin [23]. A similar result was obtained by Rolland et al with porcine skin and microparticles [24]. The porcine skin is hairy and the follicular ducts, of which diameter is tens of micron, are proposed to the path way for the penetration of the microparticles.…”

Recent Advances in Drug Delivery Systems

“…It was found that microparticles ranging from 3 -10 µm selectively penetrate the follicular ducts, whereas particles larger than 10 µm remain randomly distributed in the hair follicles and stratum corneum [130]. Moreover, 5 µm PLGA microparticles were visualized in the follicular ducts, while 1 µm was randomly distributed into the stratum corneum and hair follicles.…”

“…Finally, the role of skin appendages is sometimes neglected due to the fact that they only represent 0.1% of the skin surface [130]. It was found that microparticles ranging from 3 -10 µm selectively penetrate the follicular ducts, whereas particles larger than 10 µm remain randomly distributed in the hair follicles and stratum corneum [130].…”

The Mystical Effects of Dermatological Vehicles

“…increased bioavailability, drug targeting within the skin etc.) is currently under debate [26, 50, 51, 52, 53]. In clinical practice, the question is often asked whether creams, gels, ointments or liposomes are better in delivering a drug to the skin in terms of promoting the drug absorption and therapeutic effect [54].…”