关键词: Amikacin Drug delivery system Keratitis Nanofiber Sustained delivery Vancomycin

Mesh : Animals Rabbits Nanofibers / chemistry Anti-Bacterial Agents / administration & dosage pharmacokinetics chemistry Polyvinyl Alcohol / chemistry Delayed-Action Preparations Staphylococcus aureus / drug effects Polyesters / chemistry Drug Liberation Administration, Ophthalmic Pseudomonas aeruginosa / drug effects Vancomycin / administration & dosage pharmacokinetics chemistry Amikacin / pharmacokinetics administration & dosage chemistry Drug Delivery Systems Drug Carriers / chemistry Male

来  源:   DOI:10.1016/j.ijpharm.2024.124056

Abstract:
Bacterial corneal keratitis is a damage to the corneal tissue that if not treated, can cause various complications like severe vision loss or even blindness. Combination therapy with two antibiotics which are effective against Gram-positive and Gram-negative bacteria offers sufficient broad-spectrum antibiotic coverage for the treatment of keratitis. Nanofibers can be a potential carrier in dual drug delivery due to their structural characteristics, specific surface area and high porosity. In order to achieve a sustained delivery of amikacin (AMK) and vancomycin (VAN), the current study designed, assessed, and compared nanofibrous inserts utilizing polyvinyl alcohol (PVA) and polycaprolactone (PCL) as biocompatible polymers. Electrospinning method was utilized to prepare two different formulations, PVA-VAN/AMK and PCL/PVA-VAN/AMK, with 351.8 ± 53.59 nm and 383.85 ± 49 nm diameters, respectively. The nanofibers were simply inserted in the cul-de-sac as a noninvasive approach for in vivo studies. The data obtained from the physicochemical and mechanical properties studies confirmed the suitability of the formulations. Antimicrobial investigations showed the antibacterial properties of synthesized nanofibers against Staphylococcus aureus and Pseudomonas aeruginosa. Both in vitro and animal studies demonstrated sustained drug release of the prepared nanofibers for 120 h. Based on the in vivo findings, the prepared nanofibers\' AUC0-120 was found to be 20 to 31 times greater than the VAN and AMK solutions. Considering the results, the nanofibrous inserts can be utilized as an effective and safe system in drug delivery.
摘要:
细菌性角膜角膜炎是对角膜组织的损害,如果不治疗,会导致各种并发症,如严重的视力丧失甚至失明。两种抗生素的联合治疗对革兰氏阳性和革兰氏阴性细菌有效,为角膜炎的治疗提供了足够的广谱抗生素覆盖。纳米纤维由于其结构特点,可以成为双重给药的潜在载体,比表面积和高孔隙率。为了实现阿米卡星(AMK)和万古霉素(VAN)的持续给药,当前的研究设计,评估,并比较了利用聚乙烯醇(PVA)和聚己内酯(PCL)作为生物相容性聚合物的纳米纤维插入物。采用静电纺丝法制备两种不同的配方,PVA-VAN/AMK和PCL/PVA-VAN/AMK,直径为351.8±53.59nm和383.85±49nm,分别。将纳米纤维简单地插入盲囊中作为用于体内研究的非侵入性方法。从物理化学和机械性能研究获得的数据证实了制剂的适用性。抗菌研究表明,合成纳米纤维对金黄色葡萄球菌和铜绿假单胞菌具有抗菌性能。体外和动物研究均表明,所制备的纳米纤维可持续释放药物120小时。发现制备的纳米纤维AUC0-120比VAN和AMK溶液大20至31倍。考虑到结果,纳米纤维插入物可用作药物递送中的有效且安全的系统。
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