1. Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug.
- Author
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Mu Y, Fu Y, Li J, Yu X, Li Y, Wang Y, Wu X, Zhang K, Kong M, Feng C, and Chen X
- Subjects
- Administration, Oral, Antineoplastic Agents administration & dosage, Caco-2 Cells, Chitosan chemical synthesis, Doxorubicin administration & dosage, Drug Carriers chemical synthesis, Drug Liberation, Humans, Micelles, Nanostructures chemistry, Particle Size, Quercetin chemical synthesis, Static Electricity, Tight Junctions metabolism, ATP Binding Cassette Transporter, Subfamily B antagonists & inhibitors, Antineoplastic Agents pharmacology, Chitosan chemistry, Doxorubicin pharmacology, Drug Carriers chemistry, Quercetin chemistry
- 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 (P
app ) 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., (Copyright © 2018. Published by Elsevier Ltd.)- Published
- 2019
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