Cui Xiaoming, Li Xiaoli, Xu Zhilu, Guan Xiuwen, Ma Jinlong, Ding Dejun, Zhang Weifen
College of Pharmacy, Weifang Medical University, Weifang, China.
Department of Pharmacy, Weifang Traditional Chinese Hospital, Weifang, China.
Front Bioeng Biotechnol. 2021 Mar 5;9:635485. doi: 10.3389/fbioe.2021.635485. eCollection 2021.
Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). The resulting NAT/CLZ@CTS/PLGA formulations were characterized by a transmission electron microscope (TEM) and release test. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. Furthermore, hemolysis, corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. Thus, good biosafety along with a significant anti-candidiasis effect are found in the NAT/CLZ@CTS/PLGA nanoparticles (NPs). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.
那他霉素（NAT）是治疗真菌性角膜炎（FK）的首选药物。然而，其固有的缺点，如溶解度差、给药频率高和治疗周期长，需要通过设计新的给药方式来紧急解决，以扩大其临床应用。越来越多的研究证实，克霉唑（CLZ）在抑制真菌生长方面发挥着重要作用。因此，本文采用同轴电喷雾（CO-ES）技术制备了平均流体动力学粒径为309-406 nm的纳米系统，用于在壳聚糖（CTS）和聚乳酸-羟基乙酸共聚物（PLGA）中共同递送NAT和CLZ。通过透射电子显微镜（TEM）和释放试验对所得的NAT/CLZ@CTS/PLGA制剂进行了表征。结果表明，该制剂具有明显的核壳结构，颗粒分布均匀，并且能够在36小时内持续释放药物。此外，还进行了溶血试验、角膜刺激性试验、局部过敏试验和抗真菌活性分析，以评估该制剂的安全性和有效性。因此，在NAT/CLZ@CTS/PLGA纳米颗粒（NPs）中发现了良好的生物安全性以及显著的抗念珠菌病效果。综上所述，结果表明该设计可能为治疗FK提供一种有前景的药物递送系统和新的选择。
