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Lactobionic/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma.

Lactobionic/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma.

Authors :
Anwar DM
Khattab SN
Helmy MW
Kamal MK
Bekhit AA
Elkhodairy KA
Elzoghby AO
Source :
Bioconjugate chemistry [Bioconjug Chem] 2018 Sep 19; Vol. 29 (9), pp. 3026-3041. Date of Electronic Publication: 2018 Aug 27.
Publication Year :
2018

Abstract

In this study, promising approaches of dual-targeted micelles and drug-polymer conjugation were combined to enable injection of poorly soluble anticancer 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 anticancer 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 a 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 overexpressed folate and asialoglycoprotein receptors. In vivo, the micelles demonstrated superior antitumor 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.

Details

Language :
English
ISSN :
1520-4812
Volume :
29
Issue :
9
Database :
MEDLINE
Journal :
Bioconjugate chemistry
Publication Type :
Academic Journal
Accession number :
30110148
Full Text :
https://doi.org/10.1021/acs.bioconjchem.8b00428