title: The role of glycyrrhetinic acid modification on preparation and evaluation of quercetin-loaded chitosan-based self-aggregates.
abstract: Quercetin (QC), a type of plant-based chemical, has been reported to own anticancer activity in vivo. However, the poor water solubility limits its pharmaceutical application. In this study, two kinds of QC-loaded self-aggregates based on O-carboxymethyl chitosan-cholic acid conjugates (CMCA) were developed to improve the drug bioavailability in which glycyrrhetinic acid (GA) modification was utilized in the nanocarrier fabrication (QC-GA-CMCA) or not (QC-CMCA). These self-aggregates were prepared by a modified ultrasound-dialysis method and the role of GA modification on the evaluation of QC-loaded self-aggregates was investigated. Transmission Electron Microscopy (TEM) images revealed the formation of spherical particles of both self-aggregates. Dynamic Light Scattering (DLS) analysis and UV-VIS spectroscopy showed that the QC-GA-CMCA had smaller size, narrower size distribution, higher drug loading and entrapment efficiency than corresponding QC-CMCA aggregates. QC-GA-CMCA showed more obvious sensitivity to acidic pH condition based on the zeta potential measurements at various pHs, and fastest drug release was observed at pH 5.7 for QC-CMCA while at pH 6.5 for QC-GA-CMCA. In addition, QC-GA-CMCA demonstrated enhanced cell cytotoxicity and higher cell apoptosis rate in vitro, and also higher AUC value and a prolonged residence time of drug in vivo.
authors: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors: Hongliang
authors: H
authors: Du
authors: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors: Mengrui
authors: M
authors: Liu
authors: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors: Xiaoye
authors: X
authors: Yang
authors: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors: Guangxi
authors: G
authors: Zhai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D065546:Drug Liberation; D006034:Glycyrrhetinic Acid / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011794:Quercetin / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013053:Spectrophotometry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C504164:O-carboxymethylchitosan; D048271:Chitosan; D011794:Quercetin; D006034:Glycyrrhetinic Acid
keywords: Cell apoptosis; Cell cytotoxicity; Chitosan; Drug release; Glycyrrhetinic acid; Pharmacokinetics; Quercetin; Self-aggregates; Zeta potential