期刊
PHARMACEUTICS
卷 14, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14040728
关键词
albumin; drug delivery system; cancer-targeted therapy; prodrug
资金
- National Research Foundation of Korea (NRF) - Korea government [NRF-2019R1A2C3006283, NRF-2021R1C1C2005460]
- KU-KIST Graduate School of Converging Science and Technology (Korea University KIST)
- Intramural Research Program of KIST
Albumin has the potential to improve the delivery of anticancer drugs by acting as a natural carrier. It can enhance the circulation time of the drugs and passively target tumors through enhanced permeability and retention. However, the delivery efficiency of exogenous albumin formulations is low, which increases the risk of systemic toxicity. Prodrugs that bind endogenous albumin have been investigated as a safer and more effective drug delivery option.
Albumin has shown remarkable promise as a natural drug carrier by improving pharmacokinetic (PK) profiles of anticancer drugs for tumor-targeted delivery. The exogenous or endogenous albumin enhances the circulatory half-lives of anticancer drugs and passively target the tumors by the enhanced permeability and retention (EPR) effect. Thus, the albumin-based drug delivery leads to a potent antitumor efficacy in various preclinical models, and several candidates have been evaluated clinically. The most successful example is Abraxane, an exogenous human serum albumin (HSA)-bound paclitaxel formulation approved by the FDA and used to treat locally advanced or metastatic tumors. However, additional clinical translation of exogenous albumin formulations has not been approved to date because of their unexpectedly low delivery efficiency, which can increase the risk of systemic toxicity. To overcome these limitations, several prodrugs binding endogenous albumin covalently have been investigated owing to distinct advantages for a safe and more effective drug delivery. In this review, we give account of the different albumin-based drug delivery systems, from laboratory investigations to clinical applications, and their potential challenges, and the outlook for clinical translation is discussed. In addition, recent advances and progress of albumin-binding drugs to move more closely to the clinical settings are outlined.
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