Biodegradable Polyhydroxyalkanoates Formed by 3- and 4-Hydroxybutyrate Monomers to Produce Nanomembranes Suitable for Drug Delivery and Cell Culture

T. Volova, A. Demidenko, A. Murueva, Alexey E. Dudaev, I. Nemtsev, E. Shishatskaya
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Abstract

Biodegradable polyhydroxyalkanoates, biopolymers of microbiological origin, formed by 3- and 4-hydroxybutyrate monomers P(3HB-co-4HB), were used to obtain nanomembranes loaded with drugs as cell carriers by electrospinning. Resorbable non-woven membranes from P(3HB-co-4HB) loaded with ceftazidime, doripinem, and actovegin have been obtained. The loading of membranes with drugs differently affected the size of fibers and the structure of membranes, and in all cases increased the hydrophilicity of the surface. The release of drugs in vitro was gradual, which corresponded to the Higuchi and Korsmeyer-Peppas models. Antibiotic-loaded membranes showed antibacterial activity against S. aureus and E. coli, in which growth inhibition zones were 41.7 ± 1.1 and 38.6 ± 1.7 mm for ceftazidime and doripinem, respectively. The study of the biological activity of membranes in the NIH 3T3 mouse fibroblast culture based on the results of DAPI and FITC staining of cells, as well as the MTT test, did not reveal a negative effect despite the presence of antibiotics in them. Samples containing actovegin exhibit a stimulating effect on fibroblasts. Biodegradable polyhydroxyalkanoates formed by 3-hydroxybutyrate and 4-hydroxybutyrate monomers provide electrospinning non-woven membranes suitable for long-term delivery of drugs and cultivation of eukaryotic cells, and are promising for the treatment of wound defects complicated by infection.
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由3-羟基丁酸酯和4-羟基丁酸酯单体形成的可生物降解的聚羟基烷酸酯,用于生产适合药物传递和细胞培养的纳米膜
以3-羟基丁酸酯和4-羟基丁酸酯单体P(3HB-co-4HB)为载体,采用静电纺丝法制备了载药纳米膜。从P(3HB-co-4HB)中获得了可吸收的无纺布膜,负载有头孢他啶、多立平和活素。药物在膜上的负载不同程度地影响了纤维的大小和膜的结构,并且在所有情况下都增加了表面的亲水性。药物在体外的释放是渐进的,符合Higuchi和Korsmeyer-Peppas模型。载药膜对金黄色葡萄球菌和大肠杆菌具有抑菌活性,头孢他啶和多立平的生长抑制区分别为41.7±1.1 mm和38.6±1.7 mm。在NIH 3T3小鼠成纤维细胞培养中,通过细胞DAPI和FITC染色以及MTT试验对膜的生物活性进行了研究,尽管存在抗生素,但未发现膜的生物活性有负面影响。含有活素的样品对成纤维细胞有刺激作用。由3-羟基丁酸酯和4-羟基丁酸酯单体形成的可生物降解聚羟基烷酸酯提供了适合于药物长期递送和真核细胞培养的静电纺丝无纺布膜,有望用于伤口缺损合并感染的治疗。
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