Hirun Namon, Kraisit Pakorn, Tantishaiyakul Vimon
Thammasat University Research Unit in Smart Materials and Innovative Technology for Pharmaceutical Applications (SMIT-Pharm), Faculty of Pharmacy, Thammasat University, Pathumthani 12120, Thailand.
Center of Excellence for Drug Delivery System, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai 90112, Thailand.
Polymers (Basel). 2022 Apr 29;14(9):1836. doi: 10.3390/polym14091836.
Herein, thermosensitive blends of poloxamer 407 (P407)/poloxamer 188 (P188)/polycarbophil (PCB) were developed in terms of maximized content of PCB (a mucoadhesive polymer) and desired temperature-dependent rheological properties of the blends as in situ gelling matrices. Maximizing PCB content while achieving the preferable rheological characteristics was accomplished through the Box-Behnken design. The quantitative effect of the polymer composition in the blends on the thermosensitive characteristics was evaluated using the fitted design model and the corresponding surface plots. The optimized P407/P188/PCB blend (OPT) was the mixture of 20.000, 7.349 and 0.595% (/) of P407, P188, and PCB, respectively. The thermosensitive micellization of OPT was investigated using differential scanning calorimetry which revealed an overlapping double endothermic peak caused by the temperature-induced micellization of pure micelles in co-existence with the micelles with attached PCB. Mixing PCB with the P407/P188 matrix promoted a more intense mucoadhesion of the blend. After incorporating metronidazole, a model hydrophilic drug, into OPT, the temperature-dependent characteristics of the hydrogel did not change. Metronidazole release from OPT was sustained by an anomalous mechanism. This optimal ternary hydrogel benefiting from thermosensitive gelling and mucoadhesive matrix might be used as a viable platform for mucoadhesive in situ gelling drug delivery.
在此，开发了泊洛沙姆407（P407）/泊洛沙姆188（P188）/聚卡波非（PCB）的热敏性共混物，其依据在于使PCB（一种粘膜粘附聚合物）的含量最大化，并使共混物具有作为原位凝胶化基质所需的温度依赖性流变特性。通过Box-Behnken设计实现了在获得较好流变特性的同时使PCB含量最大化。使用拟合设计模型和相应的表面图评估了共混物中聚合物组成对热敏特性的定量影响。优化后的P407/P188/PCB共混物（OPT）分别是P407、P188和PCB的20.000%、7.349%和0.595%（/）的混合物。使用差示扫描量热法研究了OPT的热敏胶束化，结果显示存在由纯胶束的温度诱导胶束化与附着有PCB的胶束共存所导致的重叠双吸热峰。将PCB与P407/P188基质混合促进了共混物更强的粘膜粘附性。将模型亲水性药物甲硝唑掺入OPT后，水凝胶的温度依赖性特性未改变。甲硝唑从OPT中的释放通过非Fickian机制持续进行。这种受益于热敏凝胶化和粘膜粘附基质的最佳三元水凝胶可作为粘膜粘附原位凝胶化药物递送的可行平台。
