Polymeric micelle nanocarriers for targeted epidermal delivery of the hedgehog pathway inhibitor vismodegib: formulation development and cutaneous biodistribution in human skin

Article Article scientifique Article Polymeric micelle nanocarriers for targeted epidermal delivery of the hedgehog pathway inhibitor vismodegib: formulation development and cutaneous biodistribution in human skin eng 2019 author Kandekar Somnath 810626 author Singhal Mayank 785743 author Sonaje Kiran 795432 author Kalia Yogeshvar 0000-0001-9049-5489 503798 667-674 10.1080/17425247.2019.1609449 30995141 1742-5247 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 (Zav 20-30 nm) increased the aqueous solubility of VSD by >8000-fold; drug content was stable after 4 weeks at 4°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 μg/cm2, 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 μm, 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. Administration, Cutaneous Anilides/administration & dosage Animals Antineoplastic Agents/administration & dosage Drug Carriers/chemistry Drug Delivery Systems Epidermis/metabolism Hedgehog Proteins/metabolism Humans Micelles Particle Size Polymers/chemistry Pyridines/administration & dosage Skin/metabolism Skin Absorption Swine Tandem Mass Spectrometry Tissue Distribution Dewey 615 31 Section des sciences pharmaceutiques 17 false Expert Opinion on Drug Delivery 16 6 3b1d67ee-351a-4a99-b30a-10d5a45e93e6 Article (Published version) Restricted 19_Kandekar_EODD.pdf 1291731 application/pdf restrictedAccess Faculté des sciences / Section des sciences pharmaceutiques

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Polymeric micelle nanocarriers for targeted epidermal delivery of the hedgehog pathway inhibitor vismodegib: formulation development and cutaneous biodistribution in human skin	Expert Opinion on Drug Delivery			2019	276	3

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Sonaje, Kiran