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包封环孢素A的尺寸可控聚乙二醇-聚乳酸纳米颗粒的免疫抑制活性

Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A.

作者信息

Tang Li, Azzi Jamil, Kwon Mincheol, Mounayar Marwan, Tong Rong, Yin Qian, Moore Robert, Skartsis Nikolaos, Fan Timothy M, Abdi Reza, Cheng Jianjun

机构信息

Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

出版信息

J Transplant. 2012;2012:896141. doi: 10.1155/2012/896141. Epub 2012 Mar 29.

DOI:10.1155/2012/896141
PMID:22545201
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3321582/
Abstract

We encapsulated cyclosporine A (CsA) in poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs) by nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100 nm in diameter with a narrow particle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio during formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum albumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1) showed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs suppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay, the IC(50) values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35 ng/mL, respectively. This nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and potentially reduced toxicity.

摘要

我们通过环孢素A（CsA）与聚（乙二醇）-b-聚（d，l-丙交酯-共-乙交酯）（PEG-PLGA）的纳米沉淀法将CsA包裹于纳米颗粒（NPs）中。所得的CsA/PEG-PLGA-NPs直径小于100纳米，粒径分布狭窄。在制剂过程中，可通过调节聚合物浓度、溶剂或水/溶剂比例来控制NP大小。聚乙二醇化的NPs在盐溶液中保持不聚集。为方便储存和运输，制备了用牛血清白蛋白冻干保护的固体NPs。CsA的释放动力学（第1天释放55.6%）显示出在体内维持治疗性CsA浓度的潜力。在T细胞试验中，游离CsA和CsA/PEG-PLGA-NPs均剂量依赖性地抑制T细胞增殖和炎性细胞因子的产生。在混合淋巴细胞反应试验中，游离CsA和CsA/PEG-PLGA-NPs的半数抑制浓度（IC50）值分别为30和35纳克/毫升。这种纳米颗粒CsA递送技术为未来高效且潜在降低毒性的免疫抑制药物靶向递送奠定了坚实基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/a34b3e5d981d/JTRAN2012-896141.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/b52602e19c6d/JTRAN2012-896141.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/41c57eebee4e/JTRAN2012-896141.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/d0ce72f3d139/JTRAN2012-896141.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/a34b3e5d981d/JTRAN2012-896141.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/b52602e19c6d/JTRAN2012-896141.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/41c57eebee4e/JTRAN2012-896141.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/d0ce72f3d139/JTRAN2012-896141.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6a9/3321582/a34b3e5d981d/JTRAN2012-896141.004.jpg

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