Abstract
Poor in vivo characteristics of gambogic acid (GA) and difficulties in industrial manufacturing of its nanocarriers have hindered its clinical translation. Therefore, a reproducible nano-drug delivery system must be developed to realize simpler manufacture and address inherent defects of GA, such as short circulation and severe side effects, in order to facilitate its clinical application. Herein, a drug self-assembled nanoparticles (NPs) consisting of a hydrophobic prodrug based on GA and oleyl alcohol (OA), as well as vitamin E-polyethylene glycol succinate (TPGS) as a shield to improve the stability of the NPs is reported. The preparation method is simple enough to stably facilitate large-scale manufacturing. The self-assembled NPs exhibit a remarkably high drug-loading capacity, and their prolonged circulation enables the NPs to demonstrate superior antitumor efficacy in both cellular and animal models. The flexible hydrophobic long chain wraps GA groups, which mitigates vascular irritation and reduces hemolysis rates. Consequently, the prodrug nano-system addresses GA-related concerns regarding stability, efficacy, and safety, offering a simple, stable, and secure nano-platform for similar candidate drugs.
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