摘要
背景:万古霉素为骨髓炎治疗首选抗生素之一,局部给药不仅能发挥其抗菌作用,而且还能大幅减少全身不良反应。目的:优选万古霉素-聚富马酸丙二醇酯/聚乳酸-羟基乙酸共聚物微球的制备工艺,并考察其体外释放行为及细胞毒性。方法:采用复乳溶剂挥发法(W1/O/W2)制备万古霉素-聚富马酸丙二醇酯/聚乳酸-羟基乙酸共聚物微球,以微球的包封率和载药量为评价指标,应用星点设计-效应面法考察聚富马酸丙二醇酯和聚乳酸-羟基乙酸共聚物质量比、聚富马酸丙二醇酯和聚乳酸-羟基乙酸共聚物与万古霉素的质量比、二氯甲烷浓度对制备工艺的影响,对结果进行多元线性回归和二项式拟合,效应面法优选最佳工艺条件,测量微球的粒径、ζ电位、体外释放行为及细胞毒性。结果与结论:(1)成功制备了微球,优选聚合物微球的最佳制备工艺为:聚富马酸丙二醇酯与聚乳酸-羟基乙酸共聚物的质量比=2.41、聚富马酸丙二醇酯/聚乳酸-羟基乙酸共聚物与药物质量比=3.56、CH2Cl2浓度为129.73 g/L,实测平均包封率为83.38%,与预测值相比偏差为0.63%;实测平均载药量为18.19%,与预测值相比偏差为0.55%;(2)最佳工艺制得微球的平均粒径为103.902μm,ζ电位为-21.5 mV;微球体外3 d后累计释药量为(22.90±0.55)%,28 d后累计释放量达(43.57±1.02)%,28 d后微球释药明显增快,42 d时累计释放量为(97.89±1.39)%;微球细胞毒性分级为1级;(3)星点设计-效应面法优化微球制备工艺预测性良好,所优化的制备工艺重现性好、简单易行,所制备的微球具有较好的体外缓释特性和生物相容性。
BACKGROUND:Vancomycin is one of the first-choice antibiotics for osteomyelitis.Local administration can not only exe rt its antibacte rial effect,but also greatly reduce systemic adverse reactions.OBJECTIVE:To optimize the preparation process of hydrochloric acid vancomycin-poly(pro pylene fumarate)/poly(lactic-co-glycolic acid)microspheres,and examine its in vitro release behavior and cytotoxicity.METHODS:The hydrochloric acid vancomycin-poly(propylene fumarate)/poly(la ctic-co-glycolic acid)microspheres were prepared by the double emulsion solvent evapo ration method{W/O/W).The encapsulation efficiency and drug loading capacity of microspheres were used as evaluation indicato rs.The effects of mass ratio of poly(propylene fumarate)and poly(la ctic-co-glycolic acid),mass ratio of poly(propylene fumarate)and poly(la ctic-co-glycolic acid)to vanco mycin and dichloromethane concentration of oil phase poly(propylene fumarate)and poly(la ctic-co-glycolic acid)on the preparation process were investigated by star point design-response surface method.The results were analyzed by multiple linear regression and binomial fitting.The effect surfa ce method was used to optimize the optimal process conditions.The particle size of microspheres,theζpotential,in vitro release behavior,and the cytotoxicity were measured.RESULTS AND CONCLUSION:(1)The hydrochloric acid vancomycin-poly(propylene fumarate)/poly(la ctic-co-glycolic acid)microspheres were successfully prepared,and the optimal preparation process of the polymer mic rospheres was as follows:poly(propylene fumarate):poly(lactic-co-glycolic acid)mass ratio=2.41;poly(pro pylene fumarate)/poly(la ctic-co-glycolic acid):pharmaceutical mass ratio=3.56;CHClconcentration of poly(propylene fumarate)/poly(lactic-co-glycolic acid)=129.73 g/L;the measured average encaps ulation efficiency was 83.38%;deviation of 0.63%compared to predicted value;the measured average drug loading was 18.19%;deviation of 0.55%compared to predicted value.(2)The average particle size of the microspheres was 103.902μm.Theζpotential was-21.5 mV.The cumulative release of the microspheres prepared with the optimal formulation was(22.90±0.55)%after 3 days,and the cumulative drug release reached(43.57±1.02)%after 28 days.After 28 days,the drug release of mic rospheres increased significantly,and the cumulative release amount was(97.89±1.39)%at 42 days.CTS classification was grade 1.(3)The microsphere preparation process optimized by the star point designresponse surfa ce method has good predictability.The optimized preparation process has good reproducibility,is simple and easy to implement,and the prepared microspheres have good in vitro sustained-release prope rties and biocompatibility.
作者
王江华
尹东锋
滕勇
乌日开西·艾依提
王晓锋
马热艳木·艾尼
蒋厚峰
帕提古丽·艾合麦提
王晶
Wang Jianghua;Yin Dongfeng;Teng Yong;Wurikaixi·Aiyiti;Wang Xiaofeng;Mareyanmu·Aini;Jiang Houfeng;Patiguli·Aihemaiti;Wang Jing(Xinjiang Medical University,Urumqi 830000,Xinjiang Uygur Autonomous Region,China;General Hospital of Xinjiang Military Region of the Chinese People’s Liberation Army,Urumqi 830000,Xinjiang Uygur Autonomous Region,China;Xinjiang University,Urumqi 830000,Xinjiang Uygur Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第16期2510-2517,共8页
Chinese Journal of Tissue Engineering Research
基金
新疆维吾尔自治区区域协同创新专项(科技援疆)计划(2019E0277)
项目负责人:滕勇。
关键词
万古霉素
聚乳酸-羟基乙酸共聚物
聚富马酸丙二醇酯
微球
复乳溶剂挥发法
星点设计-效应面法
体外释药
细胞毒性
vacomycin
poly(lactic-co-glycolic acid)
poly(propylene fumarate)
microspheres
emulsion solvent evaporation method
star point design-response surface method
in vitro drug release
cytotoxicity
