Development of microparticles prepared by spray-drying as a vaccine delivery system against brucellosis

Development of microparticles prepared by spray-drying as a vaccine delivery system against brucellosis
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DOI:
10.1016/s0378-5173(02)00212-0
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发表时间:
2002-08-21
影响因子:
5.8
通讯作者:
Blanco-Príeto, MJ
Blanco-Príeto, MJ
中科院分区:
医学2区
文献类型:
--
作者:
Murillo, M;Gamazo, C;Blanco-Príeto, MJ

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采用喷雾干燥技术将绵羊布鲁氏菌抗原提取物热盐水与不同的聚酯(聚丙交酯-共-乙交酯RG502H[PLGA],并与聚-F-己内酯[PEC]共混)微胶囊化,以获得小于5μm的微粒。对微粒进行了包封效率、释放研究、体外释放介质的酸化和体外 J744 巨噬细胞实验(制剂的吞噬作用和毒性)测试,以确定用于疫苗接种目的的最佳配方。不含 PCL 的制剂显示出最高的包封效率,但差异并不显着。体外释放动力学的特点是孵育 1 小时后出现高爆发效应,随后缓慢且持续释放。对于基于 PLGA 的制剂,释放过程中介质的 pH 值从 7.4 下降至 3.5,而 PEC 的存在减弱了 pH 值的下降。通过 MTT 测定,所有制剂均显示出轻毒性,但在吞噬作用方面观察到差异,因为用 PEC 制备的颗粒显示出 J744 巨噬细胞和细胞呼吸爆发的更高摄取,这通过过氧化氢释放来确定。所有这些特征表明含有较高比例PEC的微粒抗原制剂易于用于动物疫苗接种研究。 (C) 2002 Elsevier Science B.V. 保留所有权利。
The antigenic extract Hot Saline from Brucella ovis was microencapsulated by the spray-drying technique with different polyesters (poly-lactide-co-glycolide RG502H [PLGA], and blends with poly-F-caprolactone [PEC]) in order to obtain microparticles smaller than 5 mum. Microparticles were tested for encapsulation efficiency, release studies, acidification of the in vitro release medium, and in vitro J744-macrophage experiments (phagocytosis and toxicity of the preparations) to determine the optimal formulation for vaccination purposes. Formulation containing no PCL showed the highest encapsulation efficiency, although the differences were not significant. The in vitro release kinetics were characterized by a high burst effect after 1 h of incubation, followed by a slow and continuos release. For the formulation based on PLGA, the pH of the medium during release dropped from 7.4 to 3.5 while the presence of PEC attenuated the pH drop. All formulations showed light toxicity by the MTT assay, but differences were observed in terms of phagocytosis, as particles prepared with PEC showed the higher uptake by J744-macrophages and cell respiratory burst, determined by oxygen peroxide release. All these characteristics suggest that the microparticulated antigenic formulation containing the higher ratio of PEC is susceptible to be used in animal vaccination studies. (C) 2002 Elsevier Science B.V. All rights reserved.