期刊
JOURNAL OF CONTROLLED RELEASE
卷 141, 期 3, 页码 277-299出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2009.10.016
关键词
Drug delivery through the skin; Skin permeation enhancement; Skin penetration; Microneedle; Transdermal carrier; Ultradeformable lipid vesicle; Transfersome (R)
The skin is refractive to most molecules, especially hydrophilic ones, despite the existence of trans-barrier pathways. It is essential to maintain this protective barrier even after breaching skin surface for purposes of transdermal drug delivery to cope with cutaneous microbiota. Mechanical abraders or local energy dischargers (porators) or else hard, sharp objects (perforators, micro-needles) can punch a limited number (-10(2)cm(-2)) of relatively wide (>= 10(3)nm) openings in the skin barrier, which then lets transiently (similar to 1day) small drug quantities (<= 10 mg) and even large molecules (and pathogens?) pass. Microscopic (>= 10(3) nm) ballistic droplets or particles also insert small drug amounts (similar to 1 mg) into the upper skin through the >= 10(6)cm(2) pores they create. The latter skin breaching method is approved for use in humans, whereas the hard nano-sized (5 nm-10 mu m) skin perforators are still in development for transdermal drug delivery. Alternatively, controlled and reliable drug delivery across skin barrier can be achieved with sufficiently deformable and stable nano-sized carriers. Such soft skin penetrators are typically composite colloids. As such they must obtain, or retain, their ability to act as drug carriers on, in, and ideally below skin barrier(s). If properly designed and applied, such self-regulating, ultra-adaptable, and stable hetero-aggregates can open spontaneously and carry drugs through <= 10(9)cm(-2) cutaneous pores in the primary skin barrier and minimise cutaneous drug clearance; this permits deep/targeted deposition and prolonged action of the carrier-transported drugs. Therapeutic products based oil ultra-adaptable, self-regulating, nano-sized (-10(2) nm) carriers are under development. The first one is already approved in Switzerland. (C) 2009 Published by Elsevier B.V.
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