A self-microemulsifying drug delivery system to overcome intestinal resveratrol toxicity and presystemic metabolism.
J Pharm Sci
; 103(11): 3491-3500, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-25103361
A mixed lipid-mixed surfactant self-microemulsifying drug delivery system (SMEDDS) was developed to exploit the health benefits of resveratrol, a Biopharmaceutical Classification System Class 2 natural polyphenol, subject to extensive intestinal presystemic metabolism. SMEDDS with a mixed lipid phase (castor oil/Capmul MCM 1:1) and a mixed surfactant phase (Kolliphor EL/Kolliphor RH 40 1:1) was developed and evaluated for its self-emulsifying properties and in vitro dispersion. The impact of SMEDDS on the permeability properties of resveratrol and its metabolite fluxes through the rat intestine and Caco-2 cells was monitored. The inhibitory effect of selected SMEDDS components on the efflux transporters multidrug resistance-associated protein and P-gp as well as cytotoxicity was assessed on Caco-2 cells. The formulation allowed for high resveratrol loading (122.5 mg/g SMEDDS), excellent self-emulsifying properties, and very rapid release. When formulated in SMEDDS, resveratrol metabolite efflux significantly declined. The formulation (SMEDDS without incorporated resveratrol) and its individual components did not compromise in vitro cell vitality and integrity. Mixed lipid-mixed surfactant SMEDDS is a prospective formulation to improve resveratrol biopharmaceutical, pharmacokinetic, and toxicological properties, leading the way to resveratrol use not only as a supplement but also as a pharmacological drug.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estilbenos
/
Tensoactivos
/
Aceite de Ricino
/
Caprilatos
/
Portadores de Fármacos
/
Glicéridos
/
Yeyuno
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Pharm Sci
Año:
2014
Tipo del documento:
Article
País de afiliación:
Eslovenia
Pais de publicación:
Estados Unidos