The Department of Physiology and Biophysics (A.R.C.), University of Mississippi Medical Center, Jackson.
the Department of Medicine (A.R.C.), University of Mississippi Medical Center, Jackson.
Hypertension. 2022 Sep;79(9):1937-1948. doi: 10.1161/HYPERTENSIONAHA.122.17944. Epub 2022 Jun 2.
The burden of acute and chronic kidney diseases to the health care system is exacerbated by the high mortality that this disease carries paired with the still limited availability of comprehensive therapies. A reason partially resides in the complexity of the kidney, with multiple potential target cell types and a complex structural environment that complicate strategies to protect and recover renal function after injury. Management of both acute and chronic renal disease, irrespective of the cause, are mainly focused on supportive treatments and renal replacement strategies when needed. Emerging preclinical evidence supports the feasibility of drug delivery technology for the kidney, and recent studies have contributed to building a robust catalog of peptides, proteins, nanoparticles, liposomes, extracellular vesicles, and other carriers that may be fused to therapeutic peptides, proteins, nucleic acids, or small molecule drugs. These fusions can display a precise renal uptake, an enhanced circulating time, and a directed intraorgan biodistribution while protecting their cargo to improve therapeutic efficacy. However, several hurdles that slow the transition towards clinical applications are still in the way, such as solubility, toxicity, and sub-optimal renal targeting. This review will discuss the feasibility and current limitations of drug delivery technologies for the treatment of renal disease, offering an update on their potential and the future directions of these promising strategies.
急性和慢性肾脏疾病给医疗系统带来的负担因该疾病的高死亡率以及综合治疗方法仍然有限而加剧。部分原因在于肾脏的复杂性，多种潜在的靶细胞类型和复杂的结构环境使得在损伤后保护和恢复肾功能的策略变得复杂。急性和慢性肾脏病的治疗，无论病因如何，主要集中在支持性治疗和必要时的肾脏替代策略上。新兴的临床前证据支持将药物输送技术应用于肾脏的可行性，最近的研究为构建肽、蛋白质、纳米颗粒、脂质体、细胞外囊泡和其他载体的丰富目录做出了贡献，这些载体可与治疗性肽、蛋白质、核酸或小分子药物融合。这些融合物可以显示精确的肾脏摄取、增强的循环时间和靶向的器官内分布，同时保护其货物以提高治疗效果。然而，仍有几个阻碍向临床应用过渡的障碍，如溶解度、毒性和不理想的肾脏靶向。本文将讨论治疗肾脏疾病的药物输送技术的可行性和当前限制，更新它们的潜力以及这些有前途的策略的未来方向。
