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

IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY Advanced drug delivery reviews Pub Date : 2024-08-13 DOI:10.1016/j.addr.2024.115429
Afsana Naaz , Heth R. Turnquist , Vijay S. Gorantla , Steven R. Little
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Abstract

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.

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移植中局部免疫调节的给药策略:缩小转化差距。
与目前临床上的金标准全身免疫抑制相比,局部免疫调节的给药策略大有可为,因为它们可以提高挽救生命或增强生命的移植手术的获益风险比。这种策略有助于在动物模型中以较低的药物剂量延长移植物的存活时间,同时最大限度地减少脱靶效应。尽管临床前动物研究取得了可喜的成果,但将这些策略推向临床试验仍面临挑战。全面了解转化障碍是临床验证临床前动物模型安全性和耐受性的有效免疫调节给药方案的关键第一步。本综述概述了目前用于移植的局部免疫调节策略的最新进展,并概述了阻碍其临床转化的主要挑战。
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来源期刊
CiteScore
28.10
自引率
5.00%
发文量
294
审稿时长
15.1 weeks
期刊介绍: The aim of the Journal is to provide a forum for the critical analysis of advanced drug and gene delivery systems and their applications in human and veterinary medicine. The Journal has a broad scope, covering the key issues for effective drug and gene delivery, from administration to site-specific delivery. In general, the Journal publishes review articles in a Theme Issue format. Each Theme Issue provides a comprehensive and critical examination of current and emerging research on the design and development of advanced drug and gene delivery systems and their application to experimental and clinical therapeutics. The goal is to illustrate the pivotal role of a multidisciplinary approach to modern drug delivery, encompassing the application of sound biological and physicochemical principles to the engineering of drug delivery systems to meet the therapeutic need at hand. Importantly the Editorial Team of ADDR asks that the authors effectively window the extensive volume of literature, pick the important contributions and explain their importance, produce a forward looking identification of the challenges facing the field and produce a Conclusions section with expert recommendations to address the issues.
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