Direct, reliable, controlled, and sustained drug delivery to female reproductive tract (FRT) remains elusive, with conventional dosage forms falling way short of the mark, leading to premature leakage, erratic drug delivery, and loss of compliance. Historically, the intravaginal route remains underserved by the pharmaceutical sector. To comprehensively address this, we turned our focus to phase-transforming sol-gels, using poloxamers, a thermosensitive polymer and, doxycycline (as hyclate salt, DOXH) as our model agent given its potential use in sexually transmitted infections (STIs). We further enhanced mucoadhesiveness through screening of differing viscosity grade hydroxypropyl methyl celluloses (HPMCs). The optimised sol-gels remained gelled at body temperature (<37 °C) and were prepared in buffer aligned to vaginal cavity pH and osmolality. Lead formulations were progressed based on their ability to retain key rheological properties, and acidic pH in the presence of simulated vaginal fluid (SVF). From a shelf-life perspective, DOXH stability, gelation temperature (T), and pH to three months (2–8 °C) was attained. In summary, the meticulously engineered, phase-transforming sol-gels provided sustained mucoretention despite dilution by vaginal fluid, paving the way for localised antimicrobial drug delivery at concentrations that potentially far exceed the minimum inhibitory concentration (MIC) for target STI-causing bacteria of the FRT.

中文翻译：

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用于通过阴道内途径持续和受控跨粘膜药物递送的相变原位凝胶

直接、可靠、受控和持续的女性生殖道 (FRT) 药物输送仍然难以实现，传统剂型远远达不到标准，导致过早泄漏、药物输送不稳定和依从性丧失。从历史上看，制药行业对阴道内途径的服务仍然不足。为了全面解决这个问题，我们将重点转向相变溶胶凝胶，使用泊洛沙姆（一种热敏聚合物）和多西环素（如盐酸，DOXH）作为我们的模型药物，因为它在性传播感染（STI）方面具有潜在用途。我们通过筛选不同粘度等级的羟丙基甲基纤维素（HPMC）进一步增强了粘膜粘附性。优化的溶胶-凝胶在体温（<37°C）下保持胶凝状态，并在与阴道腔 pH 值和渗透压一致的缓冲液中制备。铅制剂的进展基于其保留关键流变特性的能力，以及在模拟阴道液 (SVF) 存在下的酸性 pH 值。从保质期的角度来看，DOXH 稳定性、胶凝温度 (T) 和 pH 值均达到三个月 (2–8 °C)。总之，精心设计的相变溶胶-凝胶尽管被阴道液稀释，但仍能提供持续的粘液滞留，为局部抗菌药物递送铺平了道路，其浓度可能远远超过引起性传播感染的目标细菌的最低抑制浓度（MIC）。 FRT。