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Polylactide‐cyclosporin A nanoparticles for targeted immunosuppression
Author(s) -
Azzi Jamil,
Tang Li,
Moore Robert,
Tong Rong,
El Haddad Najib,
Akiyoshi Takurin,
Mfarrej Bechara,
Yang Sunmi,
Jurewicz Mollie,
Ichimura Takaharu,
Lindeman Neal,
Cheng Jianjun,
Abdi Reza
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-154690
Subject(s) - toxicity , pharmacology , chemistry , lymph , t cell , drug delivery , immunosuppression , immune system , medicine , immunology , pathology , organic chemistry
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 IC 50 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.—Azzi, J., Tang, L., Tong, R., El Haddad, N., Akiyoshi, T., Mfarrej, B., Moore, R., Yang, S., Jurewicz, M., Ichimura, T., Lindeman, N., Cheng, J., Abdi, R. Polylactide‐cyclosporin A nanoparticles for targeted immunosuppression. FASEB J. 24, 3927–3938 (2010). www.fasebj.org