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将黏附性聚合物基质和脂质体联合用于咪康唑的局部递药:治疗口腔念珠菌病的新方法。

Association of mucoadhesive polymeric matrices and liposomes for local delivery of miconazole: A new approach for the treatment of oral candidiasis.

机构信息

Department of Pharmacy and Biotechnology, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Edificio Polifunzionale, 87036 Arcavacata di Rende, Cosenza, Italy.

出版信息

Int J Pharm. 2024 Aug 15;661:124461. doi: 10.1016/j.ijpharm.2024.124461. Epub 2024 Jul 10.

Abstract

Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP). The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC). MN-loaded LP measured 284.7 ± 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 ± 3.3 %) and positive zeta potential (+47.4 ± 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis.

摘要

由于口腔念珠菌病的局部治疗通常需要长期使用抗真菌药物,因此理想的剂型应能够延长药物释放时间,确保在感染部位达到足够的药物浓度。在这种情况下,我们考虑了通过黏膜黏附聚合物基质经口腔递送硝酸咪康唑(MN)的可能性。通过利用脂质体(LP)的两亲性,使亲水性基质能够负载抗真菌药物。载药 LP 通过薄膜蒸发法和挤出法制备,而固体基质则通过将 LP 混悬液冷冻干燥在基于壳聚糖(CH)、透明质酸钠(HYA)或羟丙基甲基纤维素(HPMC)的聚合物溶液中获得。载 MN 的 LP 的粒径为 284.7±20.1nm,具有均匀的粒径分布、较高的药物包封效率(86.0±3.3%)和正的 ζ 电位(+47.4±3.3)。CH 和 HYA 基配方在 24 小时后几乎完全抑制了白色念珠菌的生长,即使 HYA 基配方释放了更多的药物。基于 CH 的基质还提供了最佳的黏膜黏附能力,因此是治疗口腔念珠菌病的最有前途的候选药物。

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