title: Enhanced oral bioavailability of nevirapine within micellar nanocarriers compared with Viramune(®).
abstract: In this work, Nevirapine (NVP) was encapsulated within three derivatives of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers (Tetronic(®) 904, 1107 and Pluronic(®) F127) with and without the addition of three pharmaceutical cosolvents (glycerin, propylene glycol and polyethylene glycol 400) over a wider range of concentrations (0-40% v/v). Also, we evaluated the effect of addition of the cosolvents on the micellar size as determined by dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM). The solubilization capacity of the systems was investigated by UV-spectrophotometry (282nm) and the systems stability was evaluated for 1 month at 25°C. Finally, oral bioavailability of the NVP-loaded micellar systems (2mg/mL) was assessed in male Wistar rats (8mg/kg) and compared with a pediatric commercially available formulation (Viramune(®)). The present study demonstrates that PEO-PPO-PEO polymeric micelles were able to enhance apparent aqueous solubility of NVP with the addition of cosolvents. Moreover, micellar nanocarriers significantly (p<0.05) improved the oral bioavailability of the drug versus Viramune(®). Overall results support the suitability of the strategy toward the development of an optimized NVP aqueous formulation to prevent HIV/AIDS mother-to-child transmission.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Moretton
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Cohen
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
authors.forename: Leandro
authors.initials: L
authors.lastname: Lepera
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Bernabeu
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; National Science Research Council (CONICET), Argentina.
authors.forename: Carlos
authors.initials: C
authors.lastname: Taira
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
authors.forename: Christian
authors.initials: C
authors.lastname: Höcht
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina; National Science Research Council (CONICET), Argentina. Electronic address: diegochiappetta@yahoo.com.ar.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Chiappetta
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers; D008297:Male; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D019829:Nevirapine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D004337:Drug Carriers; D008823:Micelles; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine
keywords: In vivo oral pharmacokinetic studies; Nevirapine; PEO–PPO–PEO block copolymers; Polymeric micelles; Viramune(®)