Johnston Deanne, Choonara Yahya E, Kumar Pradeep, du Toit Lisa C, van Vuuren Sandy, Pillay Viness
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown 2193, Johannesburg, South Africa.
Biomed Res Int. 2013;2013:460936. doi: 10.1155/2013/460936. Epub 2013 Nov 14.
In vitro analysis of drug release and antimicrobial activity of the coblended crosslinked polymeric fibre device (PFD) were investigated. The fibre loaded with ciprofloxacin and diclofenac sodium was comprised of alginate and glycerol crosslinked with barium cations. The pH dependent drug release was evident with ciprofloxacin and diclofenac sodium diffusing from the fibre at pH 4.0 compared to pH 6.8, where the fibre swelled and eroded resulting in zero-order drug release. Agar diffusion studies followed by minimum inhibitory assays were conducted to determine the antimicrobial activity of the device against Escherichia coli, Enterococcus faecalis, and Streptococcus mutans. The antimicrobial activity of the PFD was confirmed in both test assays against all test pathogens. The MIC ranges at pH 4.0 for E. coli, E. faecalis, and S. mutans were 0.5-0.8, 0.4-1.1, and 0.7-2.1 μg/mL, respectively. At pH 6.8, similar efficacies (0.3-0.5 μg/mL for E. coli and E. faecalis and 0.6-1.0 μg/mL for S. mutans) were observed. The effect of varying the plasticizer and crosslinking ion concentration on drug release profile of the fibers was further elucidated and conceptualized using molecular mechanics energy relationships (MMER) and by exploring the spatial disposition of geometrically minimized molecular conformations.
对共混交联聚合物纤维装置(PFD)的药物释放和抗菌活性进行了体外分析。负载环丙沙星和双氯芬酸钠的纤维由与钡阳离子交联的藻酸盐和甘油组成。环丙沙星和双氯芬酸钠在pH 4.0时从纤维中扩散出来,而在pH 6.8时纤维膨胀并侵蚀,导致药物零级释放,pH依赖性药物释放明显。进行了琼脂扩散研究,随后进行最小抑菌试验,以确定该装置对大肠杆菌、粪肠球菌和变形链球菌的抗菌活性。在针对所有测试病原体的两种测试中均证实了PFD的抗菌活性。在pH 4.0时,大肠杆菌、粪肠球菌和变形链球菌的最低抑菌浓度范围分别为0.5 - 0.8、0.4 - 1.1和0.7 - 2.1μg/mL。在pH 6.8时,观察到类似的效果(大肠杆菌和粪肠球菌为0.3 - 0.5μg/mL,变形链球菌为0.6 - 1.0μg/mL)。使用分子力学能量关系(MMER)并通过探索几何最小化分子构象的空间布局,进一步阐明并概念化了改变增塑剂和交联离子浓度对纤维药物释放曲线的影响。