ABSTRACT
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.
Author contributions
S Kandekar was involved in conception, design, performing experiments and analysis of data and manuscript writing. M Singhal and K Sonaje were involved in conception and guidance to perform experiments. Y Kalia was involved in conception and design, data analysis and manuscript writing.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed here.