The aim of this study was to synthesize polymeric excipients that can form mucoadhesive hydrogels containing amphotericin B (AmB) for the treatment of mucosal leishmaniasis. 2-(2-Acryloylaminoethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinyl pyrrolidone to obtain thiolated polyvinylpyrrolidone (PVP) that was then complexed with AmB to improve its solubility. The resulting structure of thiolated PVP was evaluated by ¹H nuclear magnetic resonance to confirm S-protected thiol groups, and the average molecular mass was determined by size exclusion chromatography. Moreover, variants of thiolated PVP–AmB were studied for the thiol content, amount of complexed AmB, cytotoxicity, mucoadhesive properties, and antileishmaniasis activity. The highest achieved degree of thiolation was 772 ± 24.64 μmol/g, and the amount of complexed AmB was 27.05 ± 0.31 μmol per g of polymer. Thiolated PVP and thiolated PVP–AmB variants (0.5% m/v) showed no cytotoxicity, whereas the equivalent concentration of free AmB reduced Caco-2 cell viability to 70% within 24 h. Thiol-functionalized PVP and PVP–AmB complexes displayed 7.66- and 7.20-fold higher adhesion to the mucosal surface in comparison to unmodified PVP and PVP–AmB, respectively. In addition, variants of thiolated PVP–AmB complexes displayed 100% antileishmaniasis activity in comparison to the 80% killing efficiency of Fungizone, which has been applied in the equivalent AmB concentration of 0.2 μg/mL. Thiol-functionalized PVP proved to be a promising novel excipient for the delivery of AmB providing enhanced solubility and improved mucoadhesive properties which are beneficial for the treatment of mucosal leishmaniasis.

中文翻译：

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硫酰化的PVP-两性霉素B复合物：一种创新的方法，用于粘膜利什曼病治疗的高度粘膜粘附凝胶。

这项研究的目的是合成可以形成包含两性霉素B（AmB）的粘膜粘附水凝胶的聚合物赋形剂，用于治疗粘膜利什曼病。将2-（2-丙烯酰基氨基乙基二硫烷基）-烟酸（ACENA）与N-乙烯基吡咯烷酮共聚以获得硫醇化的聚乙烯吡咯烷酮（PVP），然后将其与AmB络合以提高其溶解度。所得硫醇化PVP的结构用¹评价H核磁共振确认S保护的硫醇基，并通过尺寸排阻色谱法测定平均分子量。此外，还研究了硫醇化PVP-AmB的变体的巯基含量，复合AmB的量，细胞毒性，粘膜粘附特性​​和抗泛乐活性。达到的最高硫醇化度为772±24.64μmol/ g，复合的AmB量为27.05±0.31μmol/ g聚合物。硫醇化的PVP和硫醇化的PVP-AmB变体（0.5％m / v）没有细胞毒性，而当量的游离AmB浓度在24 h内将Caco-2细胞活力降低至70％。与未修饰的PVP和PVP-AmB相比，硫醇官能化的PVP和PVP-AmB复合物对粘膜表面的粘附力分别高7.66和7.20倍。此外，巯基化的PVP-AmB复合物的变体显示出100％的抗疟疾活性，而Fungizone的杀灭效率为80％，后者已在0.2μg/ mL的当量AmB浓度下使用。硫醇官能化的PVP被证明是一种有前途的新型赋形剂，可用于AmB的递送，具有增强的溶解性和改善的粘膜粘附特性​​，对治疗粘膜利什曼病很有帮助。