tailieunhanh - Báo cáo y học: "Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide/;

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide. | Sassi et al. AIDS Research and Therapy 2011 8 27 http content 8 1 27 AIDS RESEARCH AND THERAPY RESEARCH Open Access Preformulation and stability in biological fluids of the retrocyclin RC-101 a potential anti-HIV topical microbicide A I zxxz s zx Z Z X D c r r I 1 2 I st-l .z ziz kZ E Oi I zs Z t zx3 D z I zx I I_I z z zd 34 I h n r D zx z -X zd r 1 4 X I r-i r zx zd zx z IV I I zx5 Alexandra B Sassi Katherine E Bunge Brian L Hood ihomas P Conrads Alexander M Cole Phalguni Gupta6 and Lisa c Rohan1 2 3 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 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