Murueva Anastasiya, Zhila Natalia, Dudaev Alexey, Shishatskaya Ekaterina, Volova Tatiana
Institute of Biophysics SB RAS, Federal Research Center "Krasnoyarsk Science Center SB RAS", 50/50 Akademgorodok, Krasnoyarsk 660036, Russia.
Siberian Federal University, 79 Svobodnyi av., Krasnoyarsk 660041, Russia.
ADMET DMPK. 2025 Mar 18;13(2):2645. doi: 10.5599/admet.2645. eCollection 2025.
The use of drug delivery systems to enhance the efficacy of existing antimicrobial drugs is one of the promising approaches to combat bacterial resistance. The simultaneous presence of a polycationic biopolymer (chitosan) and an antibacterial drug (ceftazidime) in polyhydroxyalkanoates microparticles is more effective since it allows such carriers to have a more pronounced therapeutic effect. In this study, chitosan-modified ceftazidime-loaded poly(3-hydroxybutyrate-3-hydroxyvalerate-3-hydroxyhexanoate) (P(3HB-3HV-3HHх)) microparticles were prepared and investigated as a drug delivery system.
The obtained microparticles were characterized in terms of their particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, drug release studies , cytotoxicity and antibacterial properties in cell cultures.
The microparticles had spherical shapes with diameters from 0.6 to 1.6 μm. The constructed chitosan-modified ceftazidime-loaded microparticles are a depot form of drug, the release of which is realized for a long time, without burst releases, corresponds to Korsmeyer-Peppas and Higuchi models. cell viability and proliferation studies on designed microparticles investigated using HaCaT (human keratinocyte skin cell lines) showed good cell proliferation. The hemolytic activity of chitosan-modified P(3HB- 3HV-3HHх) microparticles evaluated by hemolysis assay demonstrated good blood compatibility. Chitosan-modified microparticles enhanced the antibacterial activity of ceftazidime, being effective against and .
Thus, the obtained drug delivery systems based on PHAs and chitosan in the form of microparticles can be promising means in treating infectious skin diseases for topical use.
利用药物递送系统提高现有抗菌药物的疗效是对抗细菌耐药性的有前景的方法之一。聚羟基脂肪酸酯微粒中同时存在聚阳离子生物聚合物(壳聚糖)和抗菌药物(头孢他啶)更有效,因为这使此类载体具有更显著的治疗效果。在本研究中,制备了壳聚糖修饰的载头孢他啶聚(3-羟基丁酸酯-3-羟基戊酸酯-3-羟基己酸酯)[P(3HB-3HV-3HHx)]微粒,并将其作为药物递送系统进行研究。
对所得微粒的粒径、多分散指数(PDI)、zeta电位、包封率、药物释放研究、细胞毒性及细胞培养中的抗菌性能进行了表征。
微粒呈球形,直径为0.6至1.6μm。构建的壳聚糖修饰的载头孢他啶微粒是一种药物储库形式,其释放可长时间实现,无突释现象,符合Korsmeyer-Peppas和Higuchi模型。使用HaCaT(人角质形成细胞皮肤细胞系)对设计的微粒进行的细胞活力和增殖研究表明细胞增殖良好。通过溶血试验评估的壳聚糖修饰的P(3HB-3HV-3HHx)微粒的溶血活性显示出良好的血液相容性。壳聚糖修饰的微粒增强了头孢他啶的抗菌活性,对[具体菌株1]和[具体菌株2]有效。
因此,所获得的基于PHA和壳聚糖的微粒形式的药物递送系统有望成为治疗感染性皮肤病的局部用药手段。