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载有特比萘芬的具有可修饰性能的支化 PLGA 基阳离子纳米粒。

Terbinafine-loaded branched PLGA-based cationic nanoparticles with modifiable properties.

机构信息

Department of Pharmaceutical Technology, Faculty of Pharmacy in Hradec Kralove, Charles University , Prague , Czech Republic.

Department of Biophysics and Physical Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University , Prague , Czech Republic.

出版信息

Pharm Dev Technol. 2019 Dec;24(10):1308-1316. doi: 10.1080/10837450.2019.1667387. Epub 2019 Sep 25.

Abstract

Although the systemic administration of terbinafine is quite well tolerated, topical treatment of the local infections is often preferred. New formulation strategies in topical antifungal therapy represent the polymeric nanoparticles (NPs). We successfully employed the originally synthesized PLGA derivatives of branched architectures of various molar masses, branching ratio, and high number of terminal hydroxyl or carboxyl groups for compounding of terbinafine loaded nanoparticles by nanoprecipitation method. Employing the polymers with tailored properties allowed us to formulate the NPs with desired particle size, loading capacity for drug, mucoadhesive properties, and drug release profile. The hydrophobicity and the polyester concentration revealed the main impact on the NPs size ranging from 100 to 600 nm. The stability of the nanosuspension is demonstrated by zeta potential >25 mV, and polydispersity index values <0.2. We used terbinafine in its less dissolved form of the base to increase the drug loading and delay the release. Cationic surfactant as stabilizer give the NPs high positive surface charge enhancing the adhesion to the mucosal surfaces. All formulations provided prolonged sustained release of terbinafine for several days. Antimicrobial potential has been proven by agar-well diffusion method.

摘要

虽然特比萘芬的全身给药具有良好的耐受性,但局部感染的局部治疗通常是首选。局部抗真菌治疗的新制剂策略代表了聚合纳米颗粒(NPs)。我们成功地使用了最初合成的具有不同摩尔质量、支化比和末端羟基或羧基数量的支化结构的 PLGA 衍生物,通过纳米沉淀法来制备载有特比萘芬的纳米颗粒。使用具有定制性能的聚合物,我们能够制备出具有所需粒径、药物载药量、粘膜粘附性和药物释放特性的 NPs。疏水性和亲聚酯浓度对 NPs 尺寸的影响最大,范围从 100 到 600nm。纳米混悬液的稳定性通过zeta 电位>25mV 和多分散指数值<0.2 来证明。我们使用了以碱的形式存在的溶解度较低的特比萘芬来增加药物负载并延迟释放。阳离子表面活性剂作为稳定剂赋予 NPs 高正表面电荷,增强了与粘膜表面的粘附性。所有制剂都提供了数天的特比萘芬持续释放。抗菌潜力已通过琼脂扩散法得到证实。

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