Cemal Shaul D, Kazimirsky Gila, Shadkchan Yana, Eswaran Lakshmanan, Abramovitch Rinat, Abudi Natalie, Cuestas Maria L, Osherov Nir, Byk Gerardo
Laboratory of Nano-Biotechnology, Dept. of Chemistry, Bar-Ilan University, Israel.
Department of Clinical Microbiology and Immunology, Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel.
Nanomedicine. 2025 Jun;66:102824. doi: 10.1016/j.nano.2025.102824. Epub 2025 Apr 23.
Biodegradable polymers have gained attention for controlled drug delivery due to their potential for sustained release. Herein, a novel series of cross-linked, narrow size nanohydrogels (NHGs) with tunable sizes (20-500 nm), devoid of toxicity, and suitable for diverse biological applications were developed. These NHGs are synthesized via a thermo-responsive self-assembly process followed by confined polymerization. Ester cross-linkers were introduced into the polymeric backbone to enhance biodegradability. The NHGs comprise ideal candidates for drug delivery due to their long circulation in blood after iv administration. The anti-oxidant curcumin and the antifungal drug amphotericin B (AmB) as hydrophobic drug models were successfully loaded. The AmB-loaded NHGs showed improved antifungal activity against clinical isolates of molds and yeasts and markedly reduced morbidity in murine models inoculated with lethal doses of the pathogenic mold Candida albicans as compared to the commercial AmB formulation Fungizone. The NHGs thereby offer a versatile platform for controlled drug release.
可生物降解聚合物因其具有持续释放的潜力而在药物控释方面受到关注。在此,我们开发了一系列新型的交联窄尺寸纳米水凝胶(NHGs),其尺寸可调(20 - 500纳米),无毒,适用于多种生物应用。这些NHGs通过热响应自组装过程随后进行受限聚合反应合成。酯类交联剂被引入到聚合物主链中以增强生物降解性。由于静脉注射后NHGs在血液中循环时间长,它们是药物递送的理想候选物。成功负载了抗氧化剂姜黄素和抗真菌药物两性霉素B(AmB)作为疏水性药物模型。与市售的两性霉素B制剂Fungizone相比,负载AmB的NHGs对临床分离的霉菌和酵母菌显示出更高的抗真菌活性,并且在接种致死剂量致病性霉菌白色念珠菌的小鼠模型中显著降低了发病率。因此,NHGs为药物控释提供了一个通用平台。