期刊
NANO LETTERS
卷 15, 期 4, 页码 2434-2441出版社
AMER CHEMICAL SOC
DOI: 10.1021/nl504829f
关键词
Nanotopography; transdermal; drug delivery; etanercept; integrin
类别
资金
- National Institutes of Health [R01-EB018842]
- Kimberly-Clark Corporation
- National Psoriasis Foundation (NPF)
Transdermal delivery of therapeutics is restricted by narrow limitations on size and hydrophobicity. Nanotopography has been shown to significantly enhance high molecular weight paracellular transport in vitro. Herein, we demonstrate for the first time that nanotopography applied to microneedles significantly enhances transdermal delivery of etanercept, a 150 kD therapeutic, in both rats and rabbits. We further show that this effect is mediated by remodeling of the tight junction proteins initiated via integrin binding to the nanotopography, followed by phosphorylation of myosin light chain (MLC) and activation of the actomyosin complex, which in turn increase paracellular permeability.
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