Gugleva Viliana, Michailova Victoria, Mihaylova Rositsa, Momekov Georgi, Zaharieva Maya Margaritova, Najdenski Hristo, Petrov Petar, Rangelov Stanislav, Forys Aleksander, Trzebicka Barbara, Momekova Denitsa
Department of Pharmaceutical Technologies, Faculty of Pharmacy, Medical University of Varna, 84 Tsar Osvoboditel Str., 9000 Varna, Bulgaria.
Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.
Pharmaceutics. 2022 Mar 30;14(4):747. doi: 10.3390/pharmaceutics14040747.
The current study describes the elaboration of a hybrid drug delivery platform for an intravesical application based on curcumin/gentamicin sulfate simultaneously loaded niosomes incorporated into thermosensitive in situ gels. Series of niosomes were elaborated via the thin film hydration method, evaluating the impact of non-ionic surfactants', cholesterol's, and curcumin's concentration. The formulation composed of equimolar ratio of Span 60, Tween 60, and 30 mol% cholesterol was selected as the optimal composition, due to the high entrapment efficiency values obtained for both drugs, and appropriate physicochemical parameters (morphology, size, PDI, and zeta potential), therefore, was further incorporated into Poloxamers (407/188) and Poloxamers and chitosan based in situ gels. The developed hybrid systems were characterized with sol to gel transition in the physiological range, suitable rheological and gelling characteristics. In addition, the formed gel structure at physiological temperatures determines the retarded dissolution of both drugs (vs. niosomal suspension) and sustained release profile. The conducted microbial studies of selected niosomal in situ gels revealed the occurrence of a synergetic effect of the two compounds when simultaneously loaded. The findings indicate that the elaborated thermosensitive niosomal in situ gels can be considered as a feasible platform for intravesical drug delivery.
本研究描述了一种用于膀胱内应用的混合药物递送平台的制备,该平台基于姜黄素/硫酸庆大霉素同时负载的脂质体,并将其掺入热敏原位凝胶中。通过薄膜水化法制备了一系列脂质体,评估了非离子表面活性剂、胆固醇和姜黄素浓度的影响。由于两种药物均获得了较高的包封率值以及合适的物理化学参数(形态、大小、多分散指数和zeta电位),因此选择由等摩尔比的司盘60、吐温60和30 mol%胆固醇组成的配方作为最佳组成,进而将其掺入泊洛沙姆(407/188)以及基于泊洛沙姆和壳聚糖的原位凝胶中。所开发的混合系统在生理范围内具有溶胶-凝胶转变特性,具备合适的流变学和胶凝特性。此外,在生理温度下形成的凝胶结构决定了两种药物(与脂质体悬浮液相比)的溶解延迟和缓释特性。对所选脂质体原位凝胶进行的微生物学研究表明,两种化合物同时负载时会产生协同效应。研究结果表明,所制备的热敏脂质体原位凝胶可被视为一种可行的膀胱内药物递送平台。