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目的制备重组降血压肽(rAHP,氨基酸序列为VLPVPR)缓释微球。方法以不同单体比和相对分子质量的乳酸-羟基乙酸共聚物(PLGA)为缓释材料,利用正交设计优化微球制备的最佳工艺条件,并考察微球的体外释药特性。结果乳酸-羟基乙酸共聚物相对分子质量越小,微球粒径越小(P<0.05),孔隙率越高;乳酸-羟基乙酸共聚物中乳酸比例越大,微球粒径越大(P<0.05);微球制备的最优工艺为:油相中乳酸-羟基乙酸共聚物质量浓度ρPLGA为12 g.100 mL-1、初乳搅拌速度Vstir为1 000 r.min-1、内水相与油相体积比Rw/o为1∶7.5,外水相聚乙烯醇124(PVA)质量浓度ρPVA为4 g.100 mL-1,按此工艺制得的重组降血压肽乳酸-羟基乙酸共聚物微球包封率在90%以上,载药量11%以上,微球粒径70～90μm;载药微球在PBS缓冲液中2 h内的累积释药量在40%以内,乳酸-羟基乙酸共聚物相对分子质量越小,释药速度越快(P<0.05),羟基乙酸含量越高释药速度也越快(P<0.05),释药曲线符合Higuchi方程,表明微球通过扩散机制进行缓释。结论该微球制备工艺成熟,包封率高,具有缓释能力。
Objective To prepare sustained-release microspheres of recombinant hypotensive peptide (rAHP, amino acid sequence VLPVPR). Methods The optimal conditions of preparation of microspheres were optimized by orthogonal design using PLGA with different monomer ratio and relative molecular mass as sustained release materials. The in vitro release characteristics of microspheres were also investigated. Results The smaller the molecular weight of lactic acid-glycolic acid copolymer was, the smaller the diameter of the microspheres was (P <0.05) and the higher the porosity was. The larger the proportion of lactic acid in the copolymer was, the larger the particle size was (P <0.05). The optimum conditions for preparation of microspheres were as follows: the mass concentration of lactic acid-glycolic acid copolymer in the oil phase was 12 g.100 mL-1, the colostrum stirring speed Vstir was 1000 r.min-1, The phase-to-oil phase volume ratio Rw / o was 1: 7.5, the external aqueous phase polyvinyl alcohol 124 (PVA) mass concentration ρPVA was 4 g.l00 mL-1, and the recombinant hypotensive peptide lactic acid-glycolic acid The encapsulation efficiency of the microspheres was over 90%, the drug loading was over 11%, the diameter of the microspheres was 70 ~ 90μm. The cumulative release of drug-loaded microspheres in PBS solution within 40% The smaller the molecular weight of glycolic acid copolymer, the faster the drug release rate (P <0.05), and the higher the content of glycolic acid was, the higher the drug release rate was (P <0.05). The drug release curve was in agreement with Higuchi equation, Mechanism for sustained release. Conclusion The preparation process of the microspheres is mature, with high entrapment efficiency and sustained release ability.