载柔红霉素和汉防己甲素的聚乳酸羟基乙酸-聚赖氨酸-聚乙二醇纳米粒的制备

Prepraration of PLGA-PLL-PEG Nanoparticles Simultaneously Loaded with Daunorubicin and Tetrandrine

目的制备包载柔红霉素-汉防己甲素的聚乳酸羟基乙酸-聚赖氨酸-聚乙二醇(PLGA-PLL-PEG)纳米粒。方法以合成高分子聚合物聚乳酸羟基乙酸-聚赖氨酸-聚乙二醇作为载体,采用复乳化溶剂挥发法制备包载柔红霉素与汉防己甲素的纳米粒;动态光散射粒径仪和透射电镜测定纳米粒的粒径分布、Zeta电位及表面形态;紫外分光光度计测定柔红霉素的包封率及载药量,HPLC测定汉防己甲素的包封率及载药量;以pH 7.4磷酸盐缓冲液(PBS)作为释放介质,考察载药纳米粒的体外释放行为。结果纳米粒平均粒径为(213.0±12)nm,Zeta电位为-19.16 mV,柔红霉素载药量为(3.63±0.15)%,包封率为(70.23±1.91)%,汉防己甲素载药量为(4.27±0.12)μg·mg-1,包封率为(86.5±0.7)%,7 d两药累积释放率大于80%。结论复乳化溶剂挥发法工艺简便可行,结果稳定,且制备的柔红霉素-汉防己甲素聚乳酸羟基乙酸-聚赖氨酸-聚乙二醇纳米粒在体外具有一定缓释效果。

OBJECTIVE To prepare PLGA-PLL-PEG nanoparticles simultaneously loaded with daunorubicln （DNR） and tetran- drine （Tet）. METHODS A functional polymer composed of PLGA, PLL and PEG was synthesized and used as a carrier material for a drug delivery system of nanoparticles. A modified double-emulsion solvent evaporation/diffusion method was used to prepare the nan- oparticles. A Zetasizer 3000HS system and transmission electron microscopy were used to determine the particle size distribution, Zeta potential and surface morphology of the nanopartieles. UV spectrophotometer and HPLC were used to determine the encapsulation efficiency and drug loading of daunorubicin. HPLC was used to determine the encapsulation efficiency and drug loading of tetrandrine, respectively. The release rates of DNR and Tet from DT-PLCA-PLL-PEG-NPs in vitro were evaluated at （ 37 ± 0. 5 ）℃ using the dialysis bag technique in pH 7. 4 phosphate buffered saline （PBS）. RESULTS The mean particle size of the nanoparticles produced by the optimized process was （213.0 ± 12） nm （ n = 3 ） with a relatively low polydispersity index [ （ 0. 075± 0. 023 ） , n = 3 ]. TEM examination showed that the nanoparticles were spherical with a smooth surface. The drug loadings were （3.63 ± 0. 15 ）% for DNR and （4. 27 ± 0. 13）% for Tet （n =3）. The entrapment efficieneies were（70. 23 ± 1.91 ）% for DNR and（86. 5 ±0. 7）% for Tet （n =3） , respectively. DNR and Tet could be sustainedly released over one week. CONCLUSION Double emulsion solvent evaporation method is simple and feasible. The prepared PLGA-PLL-PEG nanoparticles loaded with DNR and Tet have significant sustained release effect.