Polylactide-cyclosporin A nanoparticles for targeted immunosuppression

Jamil Azzi, Li Tang, Robert Moore, Rong Tong, Najib El Haddad, Takurin Akiyoshi, Bechara Mfarrej, Sunmi Yang, Mollie Jurewicz, Takaharu Ichimura, Neal Lindeman, Jianjun Cheng, Reza Abdi

Research output: Contribution to journalArticlepeer-review

Abstract

Polymeric nanoparticles (NPs), prepared via coprecipitation of drugs and polymers, are promising drug delivery vehicles for treating diseases with improved efficacy and reduced toxicity. Here, we report an unprecedented strategy for preparing polylactide-cyclosporine A (PLA-CsA) NPs (termed CsA-NPs) through CsA-initiated ring-opening polymerization of lactide (LA) followed by nanoprecipitation. The resulting CsA-NPs have sub-100 nm sizes and narrow particle size distributions, and release CsA in a sustained manner without a "burst"-release effect. Both free CsA and CsA-NPs displayed comparable suppression of T-cell proliferation and production of inflammatory cytokines in various T-cell assays in a dose-dependent manner. The IC50 values for CsA and CsA-NPs were 27.5 and 72.0 ng/ml, respectively. As lymph nodes are the main loci for T-cell activation, we coupled dendritic cells (DCs) with CsA-NPs and successfully delivered CsA selectively to the lymph nodes. Our studies indicated that CsA-NPs could be internalized in the DCs with a sustained release of CsA to the culture medium, suppressing alloreactive T-cell proliferation. Allogeneic DCs loaded with CsA-NPs were able to migrate to the draining lymph nodes where the T-cell priming was significantly reduced without any systemic release. This innovative nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and reduced toxicity.

Original languageEnglish (US)
Pages (from-to)3927-3938
Number of pages12
JournalFASEB Journal
Volume24
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • CsA toxicity
  • Dendritic cells
  • Targeted delivery

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

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