Pre-clinical Research Of Nifeviroc And F18 Microemulsion Complex As Microbicide

This report describes studies using Solutol HS15 as solubilizer and the development of a HPLC-based quantitative method for the analysis of F18 and Nifeviroc mixture. The separation was performed on a GL Science Inertsil ODS column (4.60*250 mm,5μm) maintained at 30℃ and monitored by an UV detector at 272 nn. Methanol (phase A) and acetic acid buffer (phase B) (65:35, v/v) was used as mobile phase to carry out isometric elution at a flow rate of 1.0ml-min-1.Nifeviroc and F18 were well separated from each other in Solutol HS15 under the conditions, with distinct peaks at 34.3 and 14.2 min, respectively. HPLC conditions established in this study allows accurate, sensitive and reproducible detection of both components, with sufficient dynamic range Nifeviroc, a synthetic small molecule and an antagonist of HIV-1 coreceptor CCR5, is a potent entry inhibitor highly specific for CCR5 isolates. Nifeviroc exhibits low toxicity, acidic stability, preferable pharmacokinetic properties and compatibility with vaginal microflora environment. A gel formulation of Nifeviroc has been developed for Phase-I clinical trial in China. F18, a chloro-derivative of calanolide A, is a non-nucleoside reverse-transcriptase inhibitor with potent inhibitory activity on viral replication. In the current study, to extend the efficacy of topical microbicide, the combination of Nifeviroc and F18 was evaluated both in vitro and in vivo models for the anti-HIV activities and cytotoxicities.The ratio of microemulsion complex is:Surfactant: Cosurfactant:Oil:Water=35:15:40:10.This resrarch focus on build a new basic microemulsion formulation for anti-HIV drugs delivery,which will be helpful in the future clinical research.