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J Control Release. 2010 Feb 15;141(3):277-99. doi: 10.1016/j.jconrel.2009.10.016. Epub 2009 Oct 20.

Nanotechnology and the transdermal route: A state of the art review and critical appraisal.

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IDEA AG, Frankfurter Ring 193a, 80807 Munich, Germany.


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 (approximately 10(2)cm(-2)) of relatively wide (> or =10(3)nm) openings in the skin barrier, which then lets transiently (approximately 1 day) small drug quantities (< or =10 mg) and even large molecules (and pathogens?) pass. Microscopic (> or =10(3)nm) ballistic droplets or particles also insert small drug amounts (approximately 1mg) into the upper skin through the > or =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 microm) 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 < or =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 on ultra-adaptable, self-regulating, nano-sized (approximately 10(2)nm) carriers are under development. The first one is already approved in Switzerland.

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