Micro and nanoparticle drug delivery systems for preventing allotransplant rejection.
Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; The Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA; The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
James D
JD
Fisher
The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA.
Abhinav P
AP
Acharya
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; The McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: srlittle@pitt.edu.
Steven R
SR
Little
D000938:Antigen-Presenting Cells / Q000276:immunology; D000963:Antimetabolites / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods; D053758:Nanoparticles / Q000627:therapeutic use*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology
D000963:Antimetabolites; D007166:Immunosuppressive Agents
Biomaterials; Biomimetic; Controlled release; Microparticles; Nanoparticles; Transplant immunology