Polymeric micelle nanocarriers for targeted epidermal delivery of the hedgehog pathway inhibitor vismodegib: formulation development and cutaneous biodistribution in human skin.
Expert Opin Drug Deliv
; 16(6): 667-674, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30995141
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 Ë3800- and Ë2300-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Piridinas
/
Sistemas de Liberação de Medicamentos
/
Proteínas Hedgehog
/
Anilidas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Expert Opin Drug Deliv
Assunto da revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça