LIPOSOMAL GELS FOR VAGINAL DELIVERY OF THE MICROBICIDE MC-1220: PREPARATION AND IN VIVO VAGINAL TOXICITY AND PHARMACOKINETICS
| Autor: | Pavlos G. Klepetsanis, John Mao, Sophia G. Antimisiaris, Christophe Claude Parsy, Spyridon Mourtas, Richard Storer |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Nano LIFE. :195-205 |
| ISSN: | 1793-9852 1793-9844 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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