期刊
AIDS RESEARCH AND THERAPY
卷 8, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1742-6405-8-27
关键词
-
资金
- National Institute of Allergy and Infectious Diseases (NIAID) [NIH 1U19 AI065430-01, AI082623]
- James B. Pendleton Charitable Trust
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000005] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024153] Funding Source: NIH RePORTER
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.
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