The role of glycyrrhetinic acid modification on preparation and evaluation of quercetin-loaded chitosan-based self-aggregates

• Glycyrrhetinic acid decorated polymer (GA-CMCA) was used to deliver quercetin (QC).
• QC-GA-CMCA had smaller size and narrower size distribution than unmodified ones.
• GA modification on conjugates could alter the in vitro release pattern of QC.
• QC-GA-CMCA showed enhanced cytotoxicity and cell apoptosis rate.
• QC-GA-CMCA could prolong drug circulation time in rats.

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.

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