Drug delivery strategies for local immunomodulation in transplantation: Bridging the translational gap

• Published in: Advanced drug delivery reviews 2024-10, Vol.213, p.115429, Article 115429
• Main Authors: Naaz, Afsana, Turnquist, Heth R., Gorantla, Vijay S., Little, Steven R.
• Format: Article
• Language: English
• Subjects: Clinical translation; Controlled release; Hydrogels; Immunosuppression; Implants; Microparticles; Nanoparticles; Transplantation rejection; Transplantation tolerance
• ISSN: 0169-409X; 1872-8294; 1872-8294
• DOI: 10.1016/j.addr.2024.115429

[Display omitted] •Nanoparticles, microparticles, hydrogels, and implants for drug delivery in transplantation.•Local release depots, targeted delivery, and intra-organ delivery of drugs and biologics to enhance allograft survival.•Challenges in clinical translation of drug delivery strategies in transplantation. Drug delivery strategies for local immunomodulation hold tremendous promise compared to current clinical gold-standard systemic immunosuppression as they could improve the benefit to risk ratio of life-saving or life-enhancing transplants. Such strategies have facilitated prolonged graft survival in animal models at lower drug doses while minimizing off-target effects. Despite the promising outcomes in preclinical animal studies, progression of these strategies to clinical trials has faced challenges. A comprehensive understanding of the translational barriers is a critical first step towards clinical validation of effective immunomodulatory drug delivery protocols proven for safety and tolerability in pre-clinical animal models. This review overviews the current state-of-the-art in local immunomodulatory strategies for transplantation and outlines the key challenges hindering their clinical translation.