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The Immunosuppressive Activity of Polymeric Micellar Formulation of Cyclosporine A: In Vitro and In Vivo Studies

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Abstract

We have previously developed micelles of methoxy poly(ethylene oxide)-b-poly(ε-caprolactone) as vehicles for the solubilization and delivery of cyclosporine A (CsA). These micelles were able to reduce the renal uptake and nephrotoxicity of CsA. The purpose of the current study was to test the efficacy of polymeric micellar formulation of CsA (PM-CsA) in suppressing immune responses by either T cells or dendritic cells (DCs). The performance of PM-CsA was compared to that of the commercially available formulation of CsA (Sandimmune®). Our results demonstrate that PM-CsA could exert a potent immunosuppressive effect similar to that of Sandimmune® both in vitro and in vivo. Both formulations inhibited phenotypic maturation of DCs and impaired their allostimulatory capacity. Furthermore, both PM-CsA and Sandimmune® have shown similar dose-dependent inhibition of in vitro T cell proliferative responses. A similar pattern was observed in the in vivo study, where T cells isolated from both PM-CsA-treated and Sandimmune®-treated mice have shown impairment in their proliferative response and IFN-γ production at similar levels. These results highlight the potential of polymeric micelles to serve as efficient vehicles for the delivery of CsA.

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ACKNOWLEDGMENTS

The authors would like to thank Elaine Moase for proof reading the manuscript. The authors would like to acknowledge financial support by research grant from Natural Sciences and Engineering Council of Canada (STPGP 336987).

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Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3133 Dentistry/Pharmacy Centre, Edmonton, Alberta, T6G 2N8, Canada

    Samar Hamdy, Anooshirvan Shayeganpour, Aws Alshamsan & Afsaneh Lavasanifar

  2. College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Azita Haddadi

  3. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

    Aws Alshamsan

  4. Faculty of Engineering, Department of Chemical and Material Engineering, University of Alberta, Edmonton, Alberta, Canada

    Hamidreza Montazeri Aliabadi & Afsaneh Lavasanifar

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  1. Samar Hamdy
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  2. Azita Haddadi
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  3. Anooshirvan Shayeganpour
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  4. Aws Alshamsan
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  5. Hamidreza Montazeri Aliabadi
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  6. Afsaneh Lavasanifar
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Correspondence to Afsaneh Lavasanifar.

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Hamdy, S., Haddadi, A., Shayeganpour, A. et al. The Immunosuppressive Activity of Polymeric Micellar Formulation of Cyclosporine A: In Vitro and In Vivo Studies. AAPS J 13, 159–168 (2011). https://doi.org/10.1208/s12248-011-9259-8

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  • DOI: https://doi.org/10.1208/s12248-011-9259-8

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