期刊
EXPERT OPINION ON DRUG DELIVERY
卷 16, 期 6, 页码 667-674出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/17425247.2019.1609449
关键词
Vismodegib; nanocarriers; basal cell carcinoma; topical delivery; polymeric micelle
Background: The aim was to investigate cutaneous delivery and biodistribution of the hedgehog pathway inhibitor, vismodegib (VSD), indicated for basal cell carcinoma (BCC), from polymeric micelle formulations under infinite/finite dose conditions. Methods: VSD-loaded micelles were characterized for drug content, particle size, and shape; a micelle gel was characterized for its rheological behavior. Cutaneous deposition and biodistribution of VSD were determined using porcine and human skin in vitro with quantification by UHPLC-MS/MS. Results: The optimal micelle solution (Z(av) 20-30 nm) increased the aqueous solubility of VSD by >8000-fold; drug content was stable after 4 weeks at 4 degrees C. Application of micelle solution and micelle gel (0.086% w/v) to human skin for 12 h under infinite dose conditions resulted in statistically equivalent VSD deposition (0.62 +/- 0.11 and 0.67 +/- 0.14 mu g/cm(2), respectively). Cutaneous biodistribution in human skin under infinite (micelle solution and gel) and finite (micelle gel) dose conditions showed that the VSD concentrations obtained in the basal epidermis, at depths of 120-200 mu m, were >3800- and >2300-fold greater than the IC50 reported for hedgehog signaling pathway inhibition in vitro. Conclusion: Cutaneous delivery of VSD from micelle-based formulations might enable targeted, topical treatment of superficial BCC with minimal risk of systemic exposure.
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