Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide
Abbreviated Journal Title
Aids Res. Ther.
BACTERIAL VAGINOSIS; VAGINAL MICROBICIDE; CELLS; PEPTIDE; PROTEIN; TRANSMISSION; CANDIDATE; INFECTION; TYPE-1; Infectious Diseases
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.
Aids Research and Therapy
"Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide" (2011). Faculty Bibliography 2010s. 1857.