The objective of this study was to evaluate the effects of nanoparticles (nanospheres and nanocapsules) of the promising antifungal 2-amino-thiophene (6CN10) and 6CN10 complexed with 2-hydroxypropyl-β-cyclodextrin (6CN10:HP-β-CD) in vitro and compared with free drug against Candida and Cryptococcus , using a microdilution method to measure susceptibility. The Candida and Cryptococcus clinical strains were identified using phenotypic methods and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF). To measure in vitro antifungal susceptibility, we used microdilution trials. Serial drug or nanoparticle dilutions were prepared according to the CLSI M27-A3 guidelines. Anti-biofilm activity was verified for Cryptococcus neoformans . All Candida isolates were sensitive to the free drug (MIC = 41.66–333.33 μg/mL) and were able to grow even at the higher concentration tested for all 6CN10 nanoparticles. However, the Cryptococcus neoformans strains presented MIC values of 0.32–83.33 μg/mL for 6CN10 nanoparticles, and MIC values of 0.1–0.2 μg/mL for 6CN10:HP-β-CD nanoparticles, i.e., 3333 times more active than the free drug (MIC values 166.66–333.33 μg/mL), and presenting activity greater than that of the reference drug amphotericin B (MIC = 0.5–0.125 μg/mL). 6CN10:HP-β-CD nanosphere also showed high anti-biofilm potential. The in vitro study showed that the nanoparticles allowed better drug efficiency against Cryptococcus than did the free drug. These results suggest that 6CN10-loaded nanoparticles may become a future alternative for cryptococcosis and candidiasis therapy. In vivo experiments are essential prior to clinical use.

中文翻译：

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在纳米颗粒中加入 2-氨基-噻吩衍生物：增强抗真菌活性

本研究的目的是评估具有前景的抗真菌 2-氨基噻吩 (6CN10) 和 6CN10 与 2-羟丙基-β-环糊精 (6CN10:HP-β-CD) 复合的纳米颗粒（纳米球和纳米胶囊）在体外并与游离药物对念珠菌和隐球菌进行比较，采用微量稀释法测定药敏。使用表型方法和基质辅助激光解吸/电离飞行时间 (MALDI-TOF) 鉴定了念珠菌和隐球菌临床菌株。为了测量体外抗真菌药的敏感性，我们使用了微量稀释试验。根据 CLSI M27-A3 指南制备系列药物或纳米颗粒稀释液。验证了新型隐球菌的抗生物膜活性。所有念珠菌分离株都对游离药物敏感（MIC = 41.66–333。33 μg/mL) 并且即使在所有 6CN10 纳米颗粒测试的更高浓度下也能够生长。然而，新型隐球菌菌株对 6CN10 纳米颗粒的 MIC 值为 0.32-83.33 μg/mL，对 6CN10:HP-β-CD 纳米颗粒的 MIC 值为 0.1-0.2 μg/mL，即活性比游离药物高 3333 倍（MIC 值 166.66–333.33 μg/mL），并且呈现出高于参考药物两性霉素 B 的活性（MIC = 0.5–0.125 μg/mL）。6CN10:HP-β-CD 纳米球也表现出很高的抗生物膜潜力。体外研究表明，与游离药物相比，纳米颗粒对隐球菌的药效更好。这些结果表明，载有 6CN10 的纳米颗粒可能成为未来隐球菌病和念珠菌病治疗的替代品。在临床使用之前，体内实验是必不可少的。