Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA, 15213, USA.
AIDS Res Ther. 2011 Jul 29;8:27. doi: 10.1186/1742-6405-8-27.
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.
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.
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.
RC-101 是一种阳离子肽类 retrocyclin 类似物，对 HIV-1 具有体外活性。肽类药物在制剂中暴露于赋形剂或体内生物体液时，通常容易发生构象变化、氧化和水解，这会影响产品的疗效。我们旨在研究 RC-101 在几种条件下的稳定性，包括存在人阴道液（HVF），从而能够有效地设计安全有效的杀微生物产品。通过 HPLC、圆二色性和质谱（LC-MS/MS）进行稳定性研究（温度、pH 值和氧化）。此外，还评估了 HVF 对配方 RC-101 的影响，使用来自健康志愿者或细菌性阴道病（BV）受试者的流体进行评估。通过 LC-MS/MS 监测 RC-101 长达 72 小时。
RC-101 在 pH 值为 3、4 和 7、25°C 和 37°C 时稳定。高浓度的过氧化氢在 24 小时内导致 RC-101 减少不到 10%。RC-101 在与正常 HVF 孵育 48 小时后被检测到；然而，在与 BV 受试者的 HVF 孵育后未被检测到。
我们的研究结果强调了预配方评估的重要性，并强调了 HVF 对杀微生物产品稳定性和疗效的影响。RC-101 在正常 HVF 中至少稳定 48 小时，表明它是杀微生物产品开发的有前途的候选物。然而，RC-101 在 BV 个体中的稳定性似乎受到损害，需要更先进的配方策略来稳定这种环境。
