Nanomedicine for immunosuppressive therapy: achievements in pre-clinical and clinical research

ABSTRACT

Introduction: Immunosuppression is the mainstay therapy in organ transplantation and autoimmune diseases. The effective clinical application of immunosuppressive agents has suffered from the emergence of systemic immunosuppression and/or individual drug side effects. Nanotechnology approaches may be used to modify the mentioned shortcomings by enhancing the delivery of immunosuppressants to target cells of the immune system, thus reducing the required dose for function, and/or reducing drug distribution to non-target tissues.

Areas covered: We provide an overview on the development of nanotechnology products for the most commonly used immunosuppressive agents. At first, the rationale for the use of nanoparticles as means for immunosuppressive therapy is discussed. This is followed by a review of major accomplishments in this area, particularly in preclinical in vivo studies.

Expert opinion: The results of research conducted in this area to date, points to a great promise for nano-medicine in increasing the bioavailability, reducing the toxicity, and/or potentiating the activity of immunosuppressive agents. It is, therefore, safe to speculate the more rapid translation of nanotechnologyin clinical immunosuppressive therapy in the near future providing to the overcoming of hurdles associated with nano-drug delivery such as high cost, inadequate reproducibility and potential safety concerns of the delivery systems themselves.

KEYWORDS:

• Immunosuppression
• drug delivery
• nanoparticles
• cyclosporine A
• tacrolimus
• corticosteroids
• methotrexate
• sirolimus
• mycophenolic acid
• mycophenolate mofetil

Article highlights

• Nano-carriers are shown to act as effective solubilizing agents for several small molecule immunosuppressants eliminating the need for the use of toxic solubilizing agents for their formulation.

• Nano-carriers with proper surface properties, size and drug release, are shown to alter the pharmacokinetics and biodistribution of immunosuppressive drugs following intravenous administration leading to improvements in their activity and/or toxicity profile.

• Administration of nano-formulations of immunosuppressive agents through non-parenteral routes has resulted in improved absorption of these agents through the skin, or the gastrointestinal tract, leading to improved systemic bioavailability for the delivered drugs.

• Strong evidence showing the absorption of intact nanoparticles from non-parenteral routes of administration leading to changes in the pharmacokinetic or biodistribution of encapsulated immunosuppressive agents is still missing.

• Targeting strategies within the context of nanotechnology has been explored for potentiating the immunosuppressive activity of certain agents.

• While it is clear that the development of nanomedicine for enhancing the performance of immunosuppressive agents has witnessed several examples of success at the preclinical stage, only a few of the developed systems have found their way to clinical trials, so far.

This box summarizes key points contained in the article.

Declaration of interest

H Al-Lawati would like to acknowledge support received from the ministry of health and the ministry of higher education, Oman for PhD study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

A Lavasanifar acknowledges financial support to related research from Natural Science and Engineering Research Council of Canada (NSERC). Canadian Institute of Health Research (CIHR) and Alberta Innovates Health Soluction.