Implantable Immunosuppressant Delivery to Prevent Rejection in Transplantation

Abstract

An innovative immunosuppressant with a minimally invasive delivery system has emerged in the biomedical field. The application of biodegradable and biocompatible polymer forms, such as hydrogels, scaffolds, microspheres, and nanoparticles, in transplant recipients to control the release of immunosuppressants can minimize the risk of developing unfavorable conditions. In this review, we summarized several studies that have used implantable immunosuppressant delivery to release therapeutic agents to prolong allograft survival. We also compared their applications, efficacy, efficiency, and safety/side effects with conventional therapeutic-agent administration. Finally, challenges and the future prospective were discussed. Collectively, this review will help relevant readers understand the different approaches to prevent transplant rejection in a new era of therapeutic agent delivery.

Keywords: immunosuppressant; implantable drug delivery; rejection; transplantation.

Figure 1

Examples of immunosuppressant targets in allograft rejection. ADCC: antibody-dependent, cell-mediated cytotoxicity; Ab: antibody; Ag: antigen; DC: dendritic cells; FasL: Fas ligand; FoxP3: forkhead box P3; IMPDH: inosine monophosphate dehydrogenase; IDO: indoleamine 2,3-dioxygenase 1; IFN-γ: interferon gamma; IL: interleukin; JAK: janus kinase; MHC: major histocompatibility complex; MMF: mycophenolate mofetil; MSCs: mesenchymal stem cells; mTOR: mammalian target of rapamycin; natural killer cells: NK cells; PDL-1: programmed cell death-1; PGE2: prostaglandin E2; SOT: solid organ transplantation; TGF-β: transforming growth factor beta; Tregs: regulatory T cells; VCA: vascularized composite allotransplantation.

Figure 2

Types of local delivery systems.