硫酸钙/PMMA复合缓释系统的体外药物释放和抗菌性能

Drug release and antibacterial properties of composite antibiotic delivery system consisted of calcium sulfate and PMMA in vitro

目的探讨硫酸钙/PMMA复合缓释系统的体外抗生素释放规律和抗菌性能,并和含万古霉素的PMMA进行比较。方法将含万古霉素的硫酸钙颗粒以单层形态嵌入含万古霉素的PMMA的表层,制备硫酸钙/PMMA复合缓释系统。将硫酸钙/PMMA复合缓释系统和含万古霉素的PMMA浸入10 m L模拟体液(SBF)中,在不同时间点进行全量换液,采用高效液相色谱法检测不同时间点全量换液的SBF中的万古霉素浓度。使用上述不同时间点全量换液的SBF进行金黄色葡萄球菌抑菌环试验,以评价硫酸钙/PMMA复合缓释系统的体外抗菌性能,与含有和未含有万古霉素的PMMA进行比较。结果硫酸钙/PMMA复合缓释系统的万古霉素硫酸钙颗粒在7周内逐渐降解。在不同时间点全量换液的SBF中,硫酸钙/PMMA复合缓释系统的万古霉素浓度均高于万古霉素PMMA的万古霉素浓度(P<0.05)。在不同时间点全量换液的SBF抑菌环试验中,硫酸钙/PMMA复合缓释系统的抑菌环均大于含万古霉素PMMA的抑菌环(P<0.05)。结论与含万古霉素的PMMA相比,硫酸钙/PMMA复合缓释系统能够释放更高浓度的万古霉素,并且能够在体外更加有效地抑制金黄色葡萄球菌的生长。

Objective To explore the antibiotic release characteristics and the antibacterial properties of the composite drug delivery system consisted of vancomycin-loaded calcium sulfate and vancomycin-loaded Poly(methyl acrylate,methyl methacrylate)(PMMA),comparing to PMMA loaded with vancomycin.Methods To obtain the composite drug delivery system,the vancomycin-loaded calcium sulfate pellets were embed into the surface layer of vancomycin-loaded PMMA spacer via monolayer morphology.The composite drug delivery system consisted of vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA or the vancomycin-loaded PMMA were immersed in sterile polyethylene containers containing 10 m L of SBF(p H 7.4),respectively.The SBF solution was fully quantitatively refreshed at different times after samples immersed in SBF.The vancomycin concentrations of the eluents obtained at different times were determined through HPLC according to the standard curve of vancomycin.The antibacterial properties of the eluents releasing from the composite drug delivery system and the vancomycin-loaded PMMA at the above different times were evaluated by the zone of inhibition for Staphylococcus aureus subsp.Aureus,comparing with the vancomycin-loaded PMMA and the PMMA without vancomycin.Results The vancomycin-loaded calcium sulfate pellets implanted into the composite drug delivery system gradually degraded and maintained a gradually degraded phase up to about 7 weeks.During the degradation of vancomycin-loaded calcium sulfate pellets,the concentration of vancomycin releasing from the composited drug delivery system consisted of vancomycin-loaded calcium sulfate and the vancomycin-loaded PMMA was higher than that releasing from the vancomycin-loaded PMMA(P<0.05).In each assay at different elution time points,the inhibition zone of the composited drug delivery system consisted of vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA was larger than the inhibition zone of the vancomycin-loaded PMMA.There were significant differences among the two groups(P<0.05).Conclusion It is aware of that the composite drug delivery system consisted of vancomycin-loaded calcium sulfate and vancomycin-loaded PMMA can release higher concentrations of antibiotics and more effectively inhibit bacteria growth in vitro,comparing to the vancomycin-loaded PMMA.