Title

Formulation Development of Retrocyclin 1 Analog RC-101 as an Anti-HIV Vaginal Microbicide Product

Authors

Authors

A. B. Sassi; M. R. Cost; A. L. Cole; A. M. Cole; D. L. Patton; P. Gupta;L. C. Rohan

Comments

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Abbreviated Journal Title

Antimicrob. Agents Chemother.

Keywords

TOPICAL MICROBICIDES; DELIVERY-SYSTEMS; PHASE-I; TRANSMISSION; PREVENTION; INFECTION; TISSUE; CELLS; ACCEPTABILITY; CHALLENGES; Microbiology; Pharmacology & Pharmacy

Abstract

RC-101 is a synthetic microbicide analog of retrocyclin, which has shown in vitro activity against X4 and R5 HIV-1. In an effort to develop a safe and effective RC-101 vaginal microbicide product, we assessed safety in ex vivo macaque and human models and efficacy using in vitro and ex vivo models. A polyvinyl-alcohol vaginal film containing RC-101 (100 mu g/film) was developed. Formulation assessment was conducted by evaluating disintegration, drug content, mechanical properties, and stability. Efficacy was evaluated by in vitro peripheral blood mononuclear cells (PBMC) assay and ex vivo human ectocervical tissue explant model. Ex vivo safety studies were conducted by exposing RC-101 to an excised monkey reproductive tract and excised human ectocervical tissue. RC-101 100 mu g films were shown to be safe to human and monkey tissue and effective against HIV-1 in vitro and ex vivo in human ectocervical tissue. The 90% inhibitory concentration (IC(90)) for RC-101 films at 2,000 mu g (IC(90) = 57.5 mu M) using an ex vivo model was 10-fold higher than the IC(90) observed using an in vitro model (IC(90) = 5.0 mu M). RC-101 films were stable for 1 month at 25 degrees C, with in vitro bioactivity maintained for up to 6 months. RC-101 was developed in a quick-dissolve film formulation that was shown to be safe in an ex vivo model and effective in in vitro and ex vivo models. RC-101 film formulations were shown to maintain bioactivity for a period of 6 months. Findings from the present study contribute to the development of a safe and effective topical microbicide product.

Journal Title

Antimicrobial Agents and Chemotherapy

Volume

55

Issue/Number

5

Publication Date

1-1-2011

Document Type

Article

Language

English

First Page

2282

Last Page

2289

WOS Identifier

WOS:000290019200058

ISSN

0066-4804

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