聚乳酸/聚乙醇酸可生物降解微球的制备及其对RNP的佐剂作用

Preparation of Biodegradable PLA/PLG Microspheres Serves as An Adjuvant of RNP

目的 制备包裹狂犬病毒核衣壳 (RNP)的PLA/PLG可生物降解微球 ,并观察其对RNP的佐剂作用。方法 以蛋白载量、包裹率、微球形态及粒径分布作为评价微球质量的指标 ,通过变换制备条件 ,获取质量较好的微球 ;观察三种不同聚合物材料制成的RNP微球在体外 37℃条件下的水解和释放 ;比较不同微球免疫效果。结果 PLA/PLG微球作为RNP载体 ,单剂接种诱生实验动物的抗NP抗体与AL(OH) 3 佐剂两次接种的滴度接近 ,但明显好于不加佐剂的对照组。结论 PLA/PLG微球对RNP具有良好的佐剂作用。

Objective To prepare biodegradable PLA/PLG microspheres used for encapsulating ribonucleoprotein(RNP)and study on the effect of it as an adjuvant.Methods Biodegradable PLA/PLG microspheres were prepared, and the quality of them were evaluated using protein loading, encapsulation rate, shape and size as indexes. The hydrolysis and release of the microspheres prepared with 3 kinds of materials were observed at 37℃ in vitro, and the immune effects of them were compared.Results At the 2nd to 4th week after immunization, the antibody titer of PLG50/50 microsphere was 2 times higher than those of PLA and PLG85/15 microspheres, and, at the 8th week, the titer of PLA microsphere reached peak value. However, all the antibody titers induced by the 3 kinds of microspheres were 5 times higher than that induced by RNP without encapsulation. The anti NP level induced by a single dose of RNP encapsulated with PLA/PLG microsphere was similar to that induced by 2 doses of RNP using Al(OH) 3 as adjuvant. However, the level was significantly higher than that induced by RNP without any adjuvant.Conclusion PLA/PLG microsphere is a good adjuvant of RNP and worth further investigation.