ABSTRACT
Within the past few decades, the number of patients on organ transplant waiting lists has increased dramatically while the number of available organs has remained constant (1). This shortage has led to a reduction in the acceptable criteria for organ transplants (“marginal” donor) and a higher risk for organ rejection. Coupled with the rise in incidence of autoimmune diseases, safer and more effective immunosuppressant medication is needed. Immunosuppressants are used to modulate and in some cases inhibit the cascade of reactions leading to an immune response. Classification of immunosuppressants is based on their mechanism of action, and each class has its own set of formulation challenges. Researchers have used several strategies to improve formulation design of these drugs to overcome some of these formulation challenges. Nanoparticle engineering [Nanocrystals, solution based dispersion by supercritical fluids (SEDS), and emulsification techniques] is one example of formulation design that can overcome formulation challenges such as poor aqueous solubility. Choice of excipients and different routes of administration of the drug can also improve bioavailability of immunosuppressants hindered by p-glycoprotein (PGP)
efflux and cytochrome P450 (CYP 3A) metabolism. Changing the route of administration of these drugs can improve targeting and absorption of the drugs (e.g. inhalation administration for lung transplantation), leading to improved therapeutic outcomes. Novel approaches to formulation design of immunosuppressant drugs have lead to enhanced therapeutic outcomes of these drugs for various disease states. While immunosuppressants are primarily used to treat solid organ (liver, kidney, heart, and lung) and tissue (bonemarrow) transplant rejection, other disorders such asmultiple sclerosis, psoriasis, ulcerative colitis, and asthma are all being aggressively treated with immunosuppressant drugs. Advanced design of drug delivery systems for delivering immunosuppressants shows promise in treating these disease states along with other autoimmune diseases. Immunosuppressant drugs are classified into one of four categories based on their mechanism of action in the body and the type of immunosuppressive effect that is observed in vivo. The categories of immunosuppressants are: glucocorticoids, immunophilin binders, cytostatics, and other immunosuppressant drugs (including monoclonal antibodies, interferons, and other proteins) (2). For the purposes of this review, novel formulations of “small” molecule drugs, including glucocorticoids, immunophilin binders, and cytostatics, will be discussed.
