Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug. (1st January 2019)

• Record Type: Journal Article
• Authors: Mu, Yuzhi; Fu, Yangmu; Li, Jing; Yu, Xiaoping; Li, Yang; Wang, Yanan; Wu, Xuanjin; Zhang, Kaichao; Kong, Ming; Feng, Chao; Chen, Xiguang
• Is Part Of: Carbohydrate polymers. Volume 203(2019)
• Page Start: 10
• Page End: 18
• Publication Date: 2019-01-01
• Subjects: Quercetin -- Chitosan -- Nano-micelles -- Oral delivery -- Enhance absorption; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2018.09.020
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: Quercetin-chitosan micelle was used as an oral delivery of doxorubicin. The drug loaded micelles could maintain stability and slowly release of drug. The micelles could promot the doxorubicin absorption by permeation enhancement. Abstract: In this study, quercetin-chitosan conjugate (QT-CS) was synthesized for oral delivery of doxorubicin (DOX) to improve its oral bioavailability by increasing its water solubility, opening tight junction and bypassing the P-glycoprotein (P-gp). The prepared QT-CS self-assembled into micelles which could encapsulate DOX with high encapsulation rate, small particle size (136.9 nm) and strong zeta potential (+16.2 mV). QT-CS-DOX micelles displayed sustained-release profile in gastrointestinal simulation fluid (pH 1.2/pH 7.4). QT-CS micelles could promote cellular uptake of doxorubicin, which was 2.2 folds higher than that of free doxorubicin. The trans epithelial electrical resistance (TEER) value of Caco-2 monolayer cells was significantly reduced (about 57%) by drug loaded QT-CS micelles, leading to a high apparent permeability coefficient ( Papp ) of doxorubicin, which was 10.17 folds higher than that of free doxorubicin. Above results indicate that QT-CS micelles are promising vehicles for the oral delivery of insoluble anticancer drugs.