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喷雾干燥壳聚糖微球用于抗原蛋白的细胞递送:物理化学性质及树突状细胞和巨噬细胞的摄取。

Spray-dried chitosan microparticles for cellular delivery of an antigenic protein: physico-chemical properties and cellular uptake by dendritic cells and macrophages.

机构信息

Department of Pharmaceutics and Industrial Pharmacy Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Pharm Res. 2013 Jun;30(6):1677-97. doi: 10.1007/s11095-013-1014-7. Epub 2013 Mar 13.

Abstract

PURPOSE

Spray-dried chitosan microparticles for cellular delivery of antigen to dendritic cells (DC) and macrophages (Mϕ) were investigated.

METHODS

Chitosan microparticles were prepared by spray drying. For comparison, poly(lactic-co-glycolic acid) (PLGA) and poly(α-butyl cyanoacrylate) (BCA) micro-/nanoparticles were generated. Bovine serum albumin (BSA) was used as a model antigen. The particles were characterized in terms of size, morphology, surface charge, surface composition, protein content, entrapment efficiency, in vitro release, and protein integrity. Additionally, they were subject to cell viability and cellular uptake study with DC and Mϕ.

RESULTS

Size of chitosan, PLGA, and BCA micro-/nanoparticles ranged between 3.11-7.18, 0.94-6.26, and 0.30-6.34 μm, respectively. Particle morphology and in vitro protein release varied, depending on polymer type, particle composition and preparation process parameters. Chitosan microparticles were cationic, while PLGA microparticles were neutral. BCA micro-/nanoparticles were either anionic or cationic, according to polymerization pH. Protein content and entrapment efficiency of chitosan and PLGA microparticles were relatively consistent. Only integrity and conformational structure of protein encapsulated in chitosan microparticles were completely retained. Chitosan and PLGA microparticles were non-toxic to DC and Mϕ, but the former were internalized more efficiently.

CONCLUSIONS

Spray-dried chitosan microparticles delivered the antigen efficiently to DC and Mϕ.

摘要

目的

研究喷雾干燥壳聚糖微球在向树突状细胞(DC)和巨噬细胞(Mϕ)递呈抗原中的作用。

方法

通过喷雾干燥制备壳聚糖微球。为了进行比较,还生成了聚(乳酸-共-乙醇酸)(PLGA)和聚(α-丁基氰基丙烯酸酯)(BCA)微/纳米颗粒。牛血清白蛋白(BSA)被用作模型抗原。根据粒径、形态、表面电荷、表面成分、蛋白含量、包封效率、体外释放和蛋白完整性对颗粒进行了表征。此外,还研究了它们对 DC 和 Mϕ 的细胞活力和细胞摄取的影响。

结果

壳聚糖、PLGA 和 BCA 微/纳米颗粒的粒径分别为 3.11-7.18、0.94-6.26 和 0.30-6.34μm。颗粒形态和体外蛋白释放因聚合物类型、颗粒组成和制备工艺参数而异。壳聚糖微球带正电荷,而 PLGA 微球呈中性。根据聚合 pH 值,BCA 微/纳米颗粒带负电荷或正电荷。壳聚糖和 PLGA 微球的蛋白含量和包封效率相对一致。只有包封在壳聚糖微球中的蛋白的完整性和构象结构得以完全保留。壳聚糖和 PLGA 微球对 DC 和 Mϕ 均无毒性,但前者的内化效率更高。

结论

喷雾干燥的壳聚糖微球可有效地将抗原递呈给 DC 和 Mϕ。

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