低相对分子质量聚乳酸及其与壳聚糖的共混为载体的药物控释研究

Low-relative-molecular-mass Poly(D,L-lactic acid) Used Alone or Blended with Chitosan as Matrices in the Controlled Drug Delivery System

以两种低黏均相对分子质量(Mη=3 595和10 306)聚乳酸及其与壳聚糖按5∶1,10∶1,20∶1,40∶1质量比共混为载体,用熔融法制备了吡虫啉控释制剂;用体外实验测定了制剂中吡虫啉的释放动力学;通过测定释放过程中释放介质水的pH,初步考察了基体的降解性能;通过测定释放实验结束时制剂残留质量,考察了基体的溶蚀性能,初步探讨了释放机理。结果表明,低相对分子质量聚乳酸及其与壳聚糖共混材料为载体,可以用于吡虫啉的控制释放,呈现扩散和溶蚀共同控制的缓慢释放,和溶蚀控制的快速释放两阶段释放规律。提高聚乳酸的相对分子质量可以减缓吡虫啉的释放,使释放特征发生从初期的快速释放和后期的缓慢释放,到初期缓慢释放和随后的快速持续释放的转变。降低聚乳酸相对分子质量或在基体中加入壳聚糖,可加大基体的溶蚀,使溶蚀控制的吡虫啉快速释放阶段提前。在Mη=10 306的聚乳酸中加入不同质量比的壳聚糖,可使释放介质水的pH约为中性,在117-336 h内调节快速释放开始时间,在228-445 h内调节释药中值时间。这种聚乳酸/壳聚糖共混载体可望在多功能型种子处理控释制剂上获得应用。

The controlled release formulations of imidacloprid were prepared by a melt method using two low viscosity-average-relative-molecular-mass poly （ D, L-lactic acid ） （ PLA ） alone or in combination with chitosan at different ratios （5：1,10：1,20：1,40：1 ）as matrix materials. The release kinetics of the formulations were investigated in vitro. The degradation of matrix in the formulations was estimated by determining the pH values of water samples obtained during release experiment, and the erosion of matrices was evaluated by measuring the dry mass of the formulation residues collected at the end of the release experiment. The release mechanism was also evaluated by fitting the release data to a generalized model. The results indicated that the PLA with viscosity - average relative molecular mass of 3 595 and 10 306 could be used alone or in combination with chitosan for the controlled release of imidacloprid, showing a slow release controlled by diffusion and erosion and a fast release controlled by erosion. An increase in the relative molecular mass of PLA resulted in a reduction in the release rates of imidacloprid,and a transition from an initial fast release followed by a slow release to an initial slow release followed by a fast constant release. Reduction in the relative molecular mass of PLA and the incorporation of chitosan in PLA matrix could alter the degradation and erosion of PLA, and cause an earlier occurrence of the fast constant release. The incorporation of chitosan in the matrix of PLA with Mη of 10 306 at different ratios could alter the release water to neutral, the initial time of fast release from 117 h to 336 h,and the ts0 value from 228 h to 445 h. Low-relative-molecular-mass PLA-chitosan matrix could thus be useful to produce multifunctional controlled release formulations for seed treatment.