Publications (2)2.18 Total impact
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ABSTRACT: MC-1220 is a highly potent and selective non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV. The objective is to develop formulations for the vaginal delivery of MC-1220 and characterize them in vitro and in vivo (drug uptake, pharmacokinetics, toxicokinetics and vaginal irritation/inflammation). Due to the low aqueous solubility of MC-1220, emulsion-type and liposomal formulations of MC-1220 were developed. After rheological property adjustment (by gelling agents), the toxicity of two types of vaginal formulations of MC-1220 (emulsion [E] and liposomal [LIP] formulations) at 0.1% (E and LIP) and 0.5% (LIP) drug concentration, towards the vaginal mucosa as well as the absorption of the drug through the vaginal epithelium were investigated, after single and multiple administrations in New Zealand white NZW rabbits, for 10 days. Vaginal irritation was found to be within the acceptable range and always lower compared to the irritation caused by positive control formulation (nonoxynol-9), for all the formulation types (and concentrations evaluated). Pharmacokinetic values measured showed that the 0.1% LIP formulation was faster and better absorbed compared to the similar concentration E formulation, although most differences were not significant due to high variations. In conclusion, both types of formulations can be considered as safe for prolonged vaginal administration of MC-1220 or other drugs.Nano LIFE. 04/2012; 01(03n04).
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ABSTRACT: The availability of an effective vaginal microbicide would be a major step toward containment of HIV transmission as well as allowing women self-protection against HIV infection. Here we evaluated the efficacy of vaginal application of the potent nonnucleoside reverse transcriptase inhibitor (NNRTI) MC 1220 against vaginal challenge of macaques with RT-SHIV, a chimeric simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT) gene of HIV-1. Challenge infection of monkeys with RT-SHIV currently represents the only nonhuman primate model available to test the anti-HIV-1 effects of NNRTIs. Two different gel formulations containing different MC 1220 concentrations were evaluated for efficacy in female rhesus macaques exposed to RT-SHIV. Five groups of five animals each were treated with two different gel compositions containing no drug, 0.1% or 0.5% MC 1220, followed by vaginal RT-SHIV challenge 30 min later. One animal in each group treated with the low concentration of MC 1220 as well as one control animal remained uninfected after vaginal challenge. By contrast, three of the animals receiving 0.5% MC 1220 remained uninfected, suggesting a threshold of the drug. Despite being negative for plasma viral RNA and absence of seroconversion, almost all uninfected animals exhibited SIV-specific T cells, either in the periphery or in lymph nodes draining the portal of virus entry. Our results make MC 1220 a promising compound for further development as a topical microbicide and warrant additional testing with improved formulation, long-lasting vaginal delivery systems, or even combinations with other inhibitors.AIDS research and human retroviruses 02/2011; 27(9):933-43. · 2.18 Impact Factor