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Research Article

Cyclosporine A: A Review of Current Oral and Intravenous Delivery Systems

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Pages 211-220 | Published online: 26 Sep 2008
 

ABSTRACT

As early as 1978, the immunosuppressive effect of cyclosporine A (CsA), a metabolite of the fungus Tolypocladium inflatum (Citation), was reported to be effective in inhibiting organ rejection in patients receiving kidney transplants from mismatched cadaver donors (Citation) and in the treatment of graft-versus-host disease in patients with acute leukemia following bone marrow transplants (Citation). Today, CsA is still indicated to prevent rejection following solid organ transplantations, prevent and treat graft-vs-host disease following bone marrow transplants, and has also been used in the treatment of autoimmune disease such as psoriasis, rheumatoid arthritis, and nephrotic syndrome (Citation). The effectiveness of CsA is derived from its ability to specifically and reversibly inhibit immunocompetent lymphocytes in the G0 and G1 phase of the cell cycle. The T-helper cells are the main target, but suppression of the T‐suppressor cells also occurs. The production and release of lymphokines, including interleukin-2 are also inhibited (Citation). CsA can be administered intravenously as well as orally in the form of a solution or a soft gelatin capsule. The following review will focus on the evolution of the emulsion-based oral formulations from the first generation as Sandimmune® to the second generation Neoral®, both products of Novartis Pharmaceutical, as well as on the Sandimmune® commercial intravenous formulation. The potential of alternative delivery systems, including micelles, micro- and nanoparticles, and liposomes, will also be discussed.

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