口服高分子微球疫苗的制备研究

Preparation of oral polymeric microspheres carrying vaccine

目的：研制口服靶向长效的包载抗原蛋白的疫苗微球。方法：以可生物降解高分子聚－Ｄ，Ｌ－乳酸－聚乙二醇（ＰＬＡ－ＰＥＧ）为基质材料。采用复合乳液溶剂蒸发技术包载外膜蛋白（ＯＭＰ）及人血清白蛋白（ＨＳＡ），制备出粒径小于２μｍ的微球。考察了制备工艺对微球粒径及蛋白含量的影响。结果：采用适当配比的聚乙烯醇（ＰＶＡ）水溶液为分散介质，可得到期望粒径的ＰＬＡ－ＰＥＧ微球。对抗原蛋白的包裹量可达１％左右，并视蛋白性质而定。表面活性剂可改善微球对蛋白的包裹条件。结论：可生物降解的ＰＬＡ－ＰＥＧ能对抗原蛋白进行有效包裹，并制得粒径小于２μｍ的微球。

OBJECTIVE:To prepare oral biodegradable polymeric microspheres with micron size carrying antigen protein outer membrane protein(OMP) for an effective immunization.METHOD:By composite emulsion solvent evaporation technique with biodegradable poly D,L lactide polyethylene glycol(PLA PEG) as matrix microspheres with sizes in 0.1～2 μm encapsulating antigen protein OMP was prepared.Human serum albumin(HSA) as a model protein was also encapsulated in the microspheres to investigate the conditions of protein encapsulation.Differential scanning calorimetry(DSC) was used for estimating the internal crystallinity of PLA PEG microspheres.UV absorbance at 283 nm was used for quantitating the amount of protein in PLA PEG microspheres.RESULTS:The aim microspheres were obtained.The OMP can be effectively encapsulated in the PLA PEG microsp heres.The nature of protein would affect the amount of protein in the microspheres.CONCLUSION:Polyvinyl alcohol(PVA) with 88% hydralyzation was suitable for preparing PLA PEG microspheres carrying antigen protein.The amount of antigen protein in the microspheres could be over 1% which was able to be used as oral vaccine microspheres.