Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems.
Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems.
复制标题
克服可生物降解药物输送系统中蛋白质和肽不稳定性的策略。
DOI：
10.1016/j.addr.2023.114904
复制
发表时间：
2023
影响因子：
16.1
通讯作者：
McHugh,KevinJ
中科院分区：
文献类型：
--
作者：
Shi,Miusi;McHugh,KevinJ
全球医药市场最近已从小分子药物转向多肽、蛋白质和核酸药物，这些药物现在占市场上最畅销的药品的大部分。虽然这些生物制剂通常提供更好的药物特异性、新的作用机制和/或增强的疗效，但它们也带来了新的挑战，包括降解的可能性增加，以及需要通过更具侵入性的给药途径频繁给药，这可能会限制患者的接触、患者的依从性，并最终限制这些药物的临床影响。控释系统通过提供对活体药物水平的卓越控制，将这些药物定位于感兴趣的组织(例如，肿瘤)，以及减少给药频率，有可能缓解这些挑战。不幸的是，由于生物制品的稳定性差，改装控制释放装置来释放生物制品已被证明是困难的。本文综述了控释肽和蛋白质的研究现状，讨论了通过包埋、储存和体内释放来稳定这些药物的现有技术，并展望了控释肽和蛋白质临床翻译的最有前途的机会。
The global pharmaceutical market has recently shifted its focus from small molecule drugs to peptide, protein, and nucleic acid drugs, which now comprise a majority of the top-selling pharmaceutical products on the market. Although these biologics often offer improved drug specificity, new mechanisms of action, and/or enhanced efficacy, they also present new challenges, including an increased potential for degradation and a need for frequent administration via more invasive administration routes, which can limit patient access, patient adherence, and ultimately the clinical impact of these drugs. Controlled-release systems have the potential to mitigate these challenges by offering superior control overin vivodrug levels, localizing these drugs to tissues of interest (e.g., tumors), and reducing administration frequency. Unfortunately, adapting controlled-release devices to release biologics has proven difficult due to the poor stability of biologics. In this review, we summarize the current state of controlled-release peptides and proteins, discuss existing techniques used to stabilize these drugs through encapsulation, storage, andin vivorelease, and provide perspective on the most promising opportunities for the clinical translation of controlled-release peptides and proteins.