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Lactobionic/folate dual-targeted amphiphilic maltodextrin-based micelles for targeted co-delivery of sulfasalazine and resveratrol to hepatocellular carcinoma.

08:00 EDT 15th August 2018 | BioPortfolio

Summary of "Lactobionic/folate dual-targeted amphiphilic maltodextrin-based micelles for targeted co-delivery of sulfasalazine and resveratrol to hepatocellular carcinoma."

In this study, promising approaches of dual-targeted micelles and drug-polymer conjugation were combined to enable injection of poorly soluble anti-cancer drugs together with site-specific drug release. Ursodeoxycholic acid (UDCA) as a hepatoprotective agent was grafted to maltodextrin (MD) via carbodiimide coupling to develop amphiphilic maltodextrin-ursodeoxycholic acid (MDCA)-based micelles. Sulfasalazine (SSZ), as a novel anti-cancer agent, was conjugated via a tumor-cleavable ester bond to MD backbone to obtain tumor-specific release whereas resveratrol (RSV) was physically entrapped within the hydrophobic micellar core. For maximal tumor-targeting, both folic acid (FA) and lactobionic acid (LA) were coupled to the surface of micelles to obtain dual-targeted micelles. The decrease of critical micelle concentration (CMC) from 0.012 to 0.006 mg/ml declares the significance of dual hydrophobicized core of micelles by both UDCA and SSZ. The dual-targeted micelles showed a great hemocompatibility, as well as enhanced cytotoxicity and internalization into HepG-2 liver cancer cells via binding to over-expressed folate and asialoglycoprotein receptors. In vivo, the micelles demonstrated superior anti-tumor effects revealed as reduction in the liver/body weight ratio, inhibition of angiogenesis and enhanced apoptosis. Overall, combined strategies of dual active targeted micelles with bioresponsive drug conjugation could be utilized as a promising approach for tumor-targeted drug delivery.

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Name: Bioconjugate chemistry
ISSN: 1520-4812
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