不同方法构建抗结核β-磷酸三钙药物缓释系统的载药和缓释性能

The drug loading capacity and controlled drug release property of beta-tricalcium phosphate/rifampicin drug delivery systems constructed by different solution adsorption methods

背景:构建药物缓释系统的常用方法静态溶液吸附法、动态溶液吸附法和真空溶液吸附法中,哪种方法可以使单纯多孔β-磷酸三钙载体负载更多的抗结核药物并维持更长的药物释放时间,目前尚不十分清楚。目的:研究不同溶液吸附法构建的抗结核多孔β-磷酸三钙药物缓释系统的载药性能和体外缓释规律。方法:分别利用静态溶液吸附法、动态溶液吸附法和真空溶液吸附法将利福平负载于多孔β-磷酸三钙中,比较这3种方法构建的药物缓释系统的载体力学强度、载药性能和药物缓释特性。结果与结论:(1)3种不同方法负载利福平后,载体间的力学强度无显著差异(P>0.05);载体负载利福平后的力学强度与负载前相比,差异均无显著性意义(P>0.05);(2)药物缓释系统体外载药实验表明,真空溶液吸附法构建的药物缓释系统单位质量载体的载药量(1.02±0.16)mg/g明显高于静态溶液吸附法(0.79±0.12)mg/g和动态溶液吸附法(0.89±0.13)mg/g(P<0.05);(3)体外释放实验表明,通过3种溶液吸附法构建的药物缓释系统其释药均存在突释现象。体外84 h,利福平在真空溶液吸附法、动态溶液吸附法和静态溶液吸附法构建的药物缓释系统中的累积释放百分比分别为(66.82±5.16)%,(79.49±3.50)%和(91.30±5.86)%(P<0.05),完全释药结束的时间分别为21.5,17.5和14.5 d(P<0.05);(4)结果提示,真空溶液吸附法构建的药物缓释系统可以负载更多的利福平并使其更持久的释放,因此,真空溶液吸附法可能更适合用来构建多孔β-磷酸三钙抗结核药物缓释系统。

BACKGROUND:The drug delivery systems(DDS)are commonly constructed by vacuum adsorption(VA),dynamic adsorption(DA)and static adsorption.Up to now,there is still no published studies that systematically evaluate the drug loading capacity and controlled drug release property of porousβ-tricalcium phosphate(β-TCP)scaffolds loading rifampicin(RFP)constructed by these three solution adsorption methods.OBJECTIVE:To investigate the drug loading capacity and controlled drug release property of porousβ-TCP scaffolds loading RFP constructed by these three solution adsorption methods.METHODS:Theβ-TCP/RFP drug delivery systems were constructed by VA,DA and SA,respectively.The mechanical strength ofβ-TCP,drug loading capacity and controlled drug release property of the three different DDS were analyzed.RESULTS AND CONCLUSION:(1)There were no differences in the mechanical strength ofβ-TCP from VA-DDS,DA-DDS and SA-DDS(P>0.05).The mechanical strength ofβ-TCP in three DDS groups was not significantly different from that of unloadingβ-TCP(P>0.05).(2)The in vitro drug loading testing indicated that the unit mass of RFP in VA-DDS[(1.02±0.16)mg/g]was significantly higher than that in SA-DDS[(0.79±0.12)mg/g]or DA-DDS[(0.89±0.13)mg/g](P<0.05).(3)The in vitro release study showed an initial burst release of RFP in the three different DDSs within the first 12 hours and after 84 hours.At 84 hours,the cumulative release of RFP from VA-DDS,DA-DDS and SA-DDS was up to(66.82±5.16)%,(79.49±3.50)%and(91.30±5.86%),respectively(P<0.05).Complete RFP release was observed at 21.5,17.5 and 14.5 days in VA-DDS,DA-DDS and SA-DDS,respectively(P<0.05).As the VA-DDS shows highest RFP loading capacity and most sustained drug release,VA is recommended for the construction of porousβ-TCP/RFP DDS.