Purpose

This study investigated surface-modified dual-responsive (bio-responsive and thermo-sensitive) micellar microgels as a novel vaginal drug delivery system (VDDS) for enhanced administration and prolonged localized efficacy.

Methods

Lipid matrices (LMs) consisting of Softisan® 154 and super-refined sunseed oil with or without PEG-4000 were prepared by fusion, loaded with a model topical vaginal drug (miconazole nitrate, MN), characterized and used to formulate MN-loaded surface-modified solid lipid microparticles (SLMs) by melt-homogenization. Surface-modified SLMs were characterized, lyophilized, and used to prepare surface-modified mucoadhesive and thermosensitive microgels (MTMs) employing three bioadhesive agents—hydroxypropylcellulose (HPC), Carbopol® 71G-NF or Polycarbophil®, each alongside two thermosensitive polymers (Kolliphor® P407 and Kolliphor® P188). The MTMs were characterized using phase transition temperature (PTT) and gelation time and evaluated for physicochemical performance, drug dissolution in simulated vaginal fluid (SVF, pH = 4.2) and stability. Antifungal efficacy of optimized (Kolliphor + HPC-based) microgels was evaluated against Candida albicans and compared with control.

Results

Solid-state characterizations confirmed amorphicity of LMs and MN-loaded LMs and stability of MN in the formulations. Viscoelastic MTMs with high drug content, PTT above room temperature, acceptable gelation times (110.00 ± 2.50 to 130.00 ± 7.80 s), and pH values suitable for VDD were obtained. Furthermore, optimized MTMs gave significantly (p < 0.05) greater prolonged drug release in SVF and higher anticandidal activity than commercial formulation (Daktarin®) and MN polymeric-hydrogel.

Conclusion

Dual-responsive micellar microgels represent a promising nonconventional formulation for prolonged localized VDD of MN.

中文翻译：

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以表面工程脂质为基质的双响应胶束微凝胶：一种控制阴道给药的新方法

目的

本研究调查了表面改性的双响应（生物响应和热敏）胶束微凝胶作为一种新型阴道给药系统 (VDDS)，用于增强给药和延长局部疗效。

方法

脂质基质 (LM) 由 Softisan® 154 和含或不含 PEG-4000 的超精制葵花籽油组成，通过融合制备，加载模型局部阴道药物（硝酸咪康唑，MN），表征并用于配制 MN 加载表面-通过熔融均质化修饰的固体脂质微粒 (SLM)。对表面改性的 SLM 进行表征、冻干并用于制备表面改性的粘膜粘附和热敏微凝胶 (MTM)，使用三种生物粘附剂——羟丙基纤维素 (HPC)、Carbopol® 71G-NF 或 Polycarbophil®，每种都与两种热敏聚合物 (Kolliphor® P407 和 Kolliphor® P188）。MTM 使用相变温度 (PTT) 和胶凝时间进行表征，并评估其理化性能、药物在模拟阴道液中的溶出度 (SVF，pH = 4.2) 和稳定性。白色念珠菌与对照相比。

结果

固态表征证实了 LM 和负载 MN 的 LM 的非晶性以及配方中 MN 的稳定性。获得了具有高药物含量、高于室温的 PTT、可接受的胶凝时间（110.00 ± 2.50 至 130.00 ± 7.80 秒）和适合 VDD 的 pH 值的粘弹性 MTM。此外， 与商业制剂 (Daktarin®) 和 MN 聚合物水凝胶相比，优化的 MTM在 SVF 中显着延长了药物释放时间（p < 0.05）和更高的抗念珠菌活性。

结论

双响应胶束微凝胶代表了一种有前途的非常规配方，用于延长 MN 的局部 VDD。