期刊
MOLECULAR PHARMACEUTICS
卷 16, 期 9, 页码 3957-3967出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b00583
关键词
lipid nanoparticles; curcumin; cisplatin; enhanced efficacy and reduced toxicity; microfluidics
资金
- Canadian Institutes of Health Research (CIHR)
- Natural Sciences and Engineering Research Council of Canada
- Canada Foundation of Innovation
- Uehara Memorial Foundation Research Fellowship
- CIHR New Investigator Salary Awards
- Angiotech Professorship in Drug Delivery
Curcumin exhibits potent anticancer activity via various mechanisms, but its in vivo efficacy has been hampered by poor solubility. Nanotechnology has been employed to deliver curcumin, but most of the reported systems suffered from low drug loading capacity and poor stability. Here, we report the development and optimization of a liposomal formulation for curcumin (Lipo-Cur) using an automated microfluidic technology. Lipo-Cur exhibited a mean diameter of 120 nm with a low polydispersity index (<0.2) and superior loading capacity (17 wt %) compared to other reported liposomal systems. Lipo-Cur increased the water solubility of curcumin by 700-fold, leading to 8-20-fold increased systemic exposure compared to the standard curcumin suspension formulation. When coadministered with cisplatin to tumor-bearing mice, Lipo-Cur augmented the antitumor efficacy of cisplatin in multiple mouse tumor models and decreased the nephrotoxicity. This is the first report demonstrating the dual effects of curcumin enabled by a nanoformulation in enhancing the efficacy and reducing the toxicity of a chemo-drug in animal models under a single and low dose administration.
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