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包裹嗜肺性细菌抗原的聚(D,L-丙交酯-共-乙交酯)和聚(L-乳酸)微球的制备与表征

Preparation and characterization of poly-(D,L-lactide-co-glycolide) and poly-(L-lactic acid) microspheres with entrapped pneumotropic bacterial antigens.

作者信息

Kofler N, Ruedl C, Klima J, Recheis H, Böck G, Wick G, Wolf H

机构信息

Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria.

出版信息

J Immunol Methods. 1996 Jun 10;192(1-2):25-35. doi: 10.1016/0022-1759(95)00267-7.

DOI:10.1016/0022-1759(95)00267-7
PMID:8699019
Abstract

Poly-(lactide-co-glycolide) microspheres with entrapped antigen have shown considerable promise as controlled release vaccines. To enhance the immunomodulatory effect of LW 50020, a bacterial lysate of seven common respiratory pathogens used perorally as an immunomodulator, we prepared poly-(D,L-lactide-co-glycolide) (PLG) and poly-(L-lactic acid) (PLA) microspheres with entrapped immunomodulator by solvent evaporation or solvent extraction double emulsion techniques. Physical properties, such as particle size, LW 50020 entrapment rate, antigen release patterns and morphological characteristics were investigated. All preparations displayed a high degree of antigen loading up to 95%, whereas size, surface morphology and antigen release patterns were significantly influenced by the method of preparation and the polymer components used. Solvent evaporation microspheres are porous particles from 0.8 micron to 2.0 microns in diameter, that show a rapid antigen release for PLG, and a moderate antigen release for PLA microspheres within 33 days. Solvent extraction microspheres have proven to be particles from 1.1 microns to 5.0 microns in diameter showing a smooth surface and a medium antigen release rate over 33 days. SDS-PAGE and immunoblotting of extracted antigen confirmed that the molecular weight and antigenicity of the immunomodulator remained unaltered by the entrapment procedure.

摘要

包裹有抗原的聚(丙交酯-共-乙交酯)微球已显示出作为控释疫苗的巨大潜力。为增强LW 50020(一种由七种常见呼吸道病原体组成的细菌裂解物,经口服用作免疫调节剂)的免疫调节作用,我们通过溶剂蒸发或溶剂萃取双乳液技术制备了包裹有免疫调节剂的聚(D,L-丙交酯-共-乙交酯)(PLG)和聚(L-乳酸)(PLA)微球。研究了其物理性质,如粒径、LW 50020包封率、抗原释放模式和形态特征。所有制剂的抗原负载率均高达95%,而粒径、表面形态和抗原释放模式受制备方法和所用聚合物成分的显著影响。溶剂蒸发微球是直径为0.8微米至2.0微米的多孔颗粒,对于PLG微球显示出快速的抗原释放,对于PLA微球在33天内显示出中等程度的抗原释放。溶剂萃取微球已被证明是直径为1.1微米至5.0微米的颗粒,表面光滑,在33天内抗原释放速率适中。对提取抗原的SDS-PAGE和免疫印迹分析证实,免疫调节剂的分子量和抗原性在包封过程中未发生改变。

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