Efavirenz-loaded PEO-PPO polymeric micelles enhance the oral bioavailaibility in the Anti-HIV Pharmacotherapy

CHIAPPETTA D.A.; HOCHT C.; TAIRA C.; SOSNIK A.

Rosario, Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2009

Sociedad Argentina de Farmacología Experimental

Aiming to improve dose adjustment features and bioavailability of efavirenz (EFV), the present work explored the suitability of encapsulation of EFV into polymeric micelles of different commercial poly(ethylene oxide)-poly(propylene oxide) block copolymers. Bioavailability of EFV after oral administration of EFV (40 mg/kg and 80 mg/kg) in a 10% F127 drug-loaded micelles solution was compared with an extemporaneous suspension obtained by manipulation of commercial capsules and an oily solution in male Wistar rats (220-250 g). Concentration of EFV in plasma samples were analyzed by HPLC-UV. Encapsulation of EFV led to a significant increase of the maximal plasma concentration (Cmax) (40 mg/kg: 2.9±0.7 mg/ml; 80 mg/kg: 7.1±1.5 mg/ml, p<0.05) when compared with suspension (40 mg/kg: 1.5±0.6 mg/ml; 80 mg/kg: 3.4±1.7 mg/ml) and oily solution (40 mg/kg: 1.8±0.7 mg/ml; 80 mg/kg: 2.7±0.6 mg/ml). F127 EFV-loaded micelles solution showed an enhanced AUC compared with both suspension and oily solution. In addition, a lower intersubject variability was found in PK parameter estimation after F127 EFV-loaded micelles solution administration. In conclusion, pharmacokinetic results support encapsulation of EFV in polymeric micelles as a strategy toward the development of an optimized EFV liquid formulation for the treatment of pediatric HIV/AIDS.