Title

Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide

Authors

Authors

A. B. Sassi; K. E. Bunge; B. L. Hood; T. P. Conrads; A. M. Cole; P. Gupta;L. C. Rohan

Comments

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Abbreviated Journal Title

Aids Res. Ther.

Keywords

BACTERIAL VAGINOSIS; VAGINAL MICROBICIDE; CELLS; PEPTIDE; PROTEIN; TRANSMISSION; CANDIDATE; INFECTION; TYPE-1; Infectious Diseases

Abstract

Background: RC-101, a cationic peptide retrocyclin analog, has in vitro activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF), enabling the efficient design of a safe and effective microbicide product. Stability studies (temperature, pH, and oxidation) were performed by HPLC, Circular Dichroism, and Mass Spectrometry (LC-MS/MS). Additionally, the effect of HVF on formulated RC-101 was evaluated with fluids collected from healthy volunteers, or from subjects with bacterial vaginosis (BV). RC-101 was monitored by LC-MS/MS for up to 72 h. Results: RC-101 was stable at pH 3, 4, and 7, at 25 and 37 degrees C. High concentrations of hydrogen peroxide resulted in less than 10% RC-101 reduction over 24 h. RC-101 was detected 48 h after incubation with normal HVF; however, not following incubation with HVF from BV subjects. Conclusions: Our results emphasize the importance of preformulation evaluations and highlight the impact of HVF on microbicide product stability and efficacy. RC-101 was stable in normal HVF for at least 48 h, indicating that it is a promising candidate for microbicide product development. However, RC-101 stability appears compromised in individuals with BV, requiring more advanced formulation strategies for stabilization in this environment.

Journal Title

Aids Research and Therapy

Volume

8

Publication Date

1-1-2011

Document Type

Article

Language

English

First Page

11

WOS Identifier

WOS:000208614500027

ISSN

1742-6405

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