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

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...

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Main Authors: Li Tang, Jamil Azzi, Mincheol Kwon, Marwan Mounayar, Rong Tong, Qian Yin, Robert Moore, Nikolaos Skartsis, Timothy M. Fan, Reza Abdi, Jianjun Cheng
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Journal of Transplantation
Online Access:http://dx.doi.org/10.1155/2012/896141
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author Li Tang
Jamil Azzi
Mincheol Kwon
Marwan Mounayar
Rong Tong
Qian Yin
Robert Moore
Nikolaos Skartsis
Timothy M. Fan
Reza Abdi
Jianjun Cheng
author_facet Li Tang
Jamil Azzi
Mincheol Kwon
Marwan Mounayar
Rong Tong
Qian Yin
Robert Moore
Nikolaos Skartsis
Timothy M. Fan
Reza Abdi
Jianjun Cheng
author_sort Li Tang
collection DOAJ
description 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 IC50 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.
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spelling doaj-art-1c09ecdf1ef148ac9ee459d0cb99d0e12025-08-20T02:01:51ZengWileyJournal of Transplantation2090-00072090-00152012-01-01201210.1155/2012/896141896141Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine ALi Tang0Jamil Azzi1Mincheol Kwon2Marwan Mounayar3Rong Tong4Qian Yin5Robert Moore6Nikolaos Skartsis7Timothy M. Fan8Reza Abdi9Jianjun Cheng10Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USATransplantation Research Center, Renal Division, Brigham and Women's Hospital; Children's Hospital Boston, Harvard Medical School, Boston, MA 02139, USADepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USATransplantation Research Center, Renal Division, Brigham and Women's Hospital; Children's Hospital Boston, Harvard Medical School, Boston, MA 02139, USADepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USADepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USATransplantation Research Center, Renal Division, Brigham and Women's Hospital; Children's Hospital Boston, Harvard Medical School, Boston, MA 02139, USATransplantation Research Center, Renal Division, Brigham and Women's Hospital; Children's Hospital Boston, Harvard Medical School, Boston, MA 02139, USADepartment of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USATransplantation Research Center, Renal Division, Brigham and Women's Hospital; Children's Hospital Boston, Harvard Medical School, Boston, MA 02139, USADepartment of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USAWe 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 IC50 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.http://dx.doi.org/10.1155/2012/896141
spellingShingle Li Tang
Jamil Azzi
Mincheol Kwon
Marwan Mounayar
Rong Tong
Qian Yin
Robert Moore
Nikolaos Skartsis
Timothy M. Fan
Reza Abdi
Jianjun Cheng
Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A
Journal of Transplantation
title Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A
title_full Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A
title_fullStr Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A
title_full_unstemmed Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A
title_short Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A
title_sort immunosuppressive activity of size controlled peg plga nanoparticles containing encapsulated cyclosporine a
url http://dx.doi.org/10.1155/2012/896141
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