Cauwenbergh Thibault, Ballet Steven, Martin Charlotte
Research Group of Organic Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050, Brussels, Belgium.
Mater Today Bio. 2024 Dec 25;31:101423. doi: 10.1016/j.mtbio.2024.101423. eCollection 2025 Apr.
Efficacy of therapeutic drugs is oftentimes limited in time by their low metabolic stability and rapid clearance mechanisms. Peptide hydrogels have been used for the physical encapsulation of a vast number of drugs in the treatment of many different disease states, thereby effectively prolonging activity profiles of these drugs. However, consistent drug loading and release is generally lacking, while the delivery of hydrophobic drugs remains problematic. Many of these shortcomings can be addressed by covalently attaching the drug to the hydrogelator, thereby creating hydrogel-drug conjugates. Their easy synthesis and functionalization, alongside their biocompatibility, makes peptide hydrogels particularly fit for this purpose. Release can readily be tuned depending on the choice of linker connecting the drug to the hydrogelator, where it can be specifically directed towards the site of action, which limits undesired side effects. By attaching appropriate targeting motifs, additional site-selectivity can be obtained. This review provides an overview of the main principles applied in the development of peptide-based hydrogel-drug conjugates, illustrated with a selection of representative examples from literature.
治疗药物的疗效常常因其低代谢稳定性和快速清除机制而在时间上受到限制。肽水凝胶已被用于在治疗许多不同疾病状态时对大量药物进行物理包封，从而有效地延长了这些药物的活性曲线。然而，通常缺乏一致的药物负载和释放，而疏水性药物的递送仍然存在问题。通过将药物共价连接到水凝胶剂上，从而形成水凝胶-药物缀合物，可以解决这些缺点中的许多问题。它们易于合成和功能化，以及它们的生物相容性，使得肽水凝胶特别适合于此目的。根据连接药物与水凝胶剂的连接子的选择，可以很容易地调节释放，在这种情况下，释放可以被特异性地导向作用部位，这限制了不良副作用。通过连接适当的靶向基序，可以获得额外的位点选择性。本综述概述了基于肽的水凝胶-药物缀合物开发中应用的主要原理，并辅以文献中精选的代表性实例进行说明。
