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

• Main Authors: Conrads Thomas P, Hood Brian L, Bunge Katherine E, Sassi Alexandra B, Cole Alexander M, Gupta Phalguni, Rohan Lisa C
• Format: Article
• Language: English
• Published: BMC 2011-07-01
• Series: AIDS Research and Therapy
• Online Access: http://www.aidsrestherapy.com/content/8/1/27

<p>Abstract</p> <p>Background</p> <p>RC-101, a cationic peptide retrocyclin analog, has <it>in vitro </it>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.</p> <p>Results</p> <p>RC-101 was stable at pH 3, 4, and 7, at 25 and 37°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.</p> <p>Conclusions</p> <p>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.</p>