Department of Pharmaceutics and Biopharmacy, Philipps-University Marburg, Ketzerbach 63, 35032 Marburg, Germany.
J Biomed Mater Res B Appl Biomater. 2011 Nov;99(2):391-8. doi: 10.1002/jbm.b.31910. Epub 2011 Sep 21.
The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance.
研究了孔隙率对磷酸钙复合材料中抗生素释放曲线的影响，以优化治疗持续时间。我们假设，通过将万古霉素盐酸盐包封到可生物降解的微球中，然后再混入磷酸钙骨水泥中，可以降低水泥基质的孔隙率对万古霉素释放的影响。通过喷雾干燥将万古霉素包封到可生物降解的聚（乳酸-共-乙醇酸）共聚物（PLGA）中；将载药微球以不同的粉末与液体比（P/L）添加到磷酸钙水泥（CPC）中，从而得到不同孔隙率的水泥复合材料。比较了直接将万古霉素盐酸盐添加到水泥液体中和用载万古霉素盐酸盐的微球改性的水泥复合材料中，不同 P/L 比对药物释放动力学的影响。扫描电子显微镜（SEM）用于可视化不同复合材料的表面和横截面形态。通过 Brunauer、Emmett 和 Teller 图（BET）确定这些基质的比表面积和孔径分布。可以清楚地表明，P/L 比的变化不仅影响水泥的孔隙率，还影响万古霉素的释放曲线。通过琼脂扩散试验成功测量了释放研究期间的抗生素活性。然而，将万古霉素盐酸盐包封到 PLGA 聚合物微球中，降低了水泥对药物释放的孔隙率影响，同时保持了嵌入物质的抗生素活性。
