Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system

The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate for intravenous paclitaxel (PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles (PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hem...

Full description

Saved in:
Bibliographic Details
Published in:Chinese journal of natural medicines 2015-12, Vol.13 (12), p.915-924
Main Authors: ZHANG, Li, ZHOU, Jian-Ping, YAO, Jing
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Antineoplastic Agents - chemistry
Antitumor activity
Apoptosis - drug effects
Conjugate
Drug Carriers - chemistry
Drug Delivery Systems - instrumentation
Drug Delivery Systems - methods
Drug Synergism
Female
Glycyrrhetinic acid
Glycyrrhetinic Acid - chemistry
Hep G2 Cells
Humans
Hyaluronic acid
Hyaluronic Acid - chemistry
Male
Mice
Paclitaxel - administration & dosage
Paclitaxel - adverse effects
Paclitaxel - chemistry
Synergistically targeted delivery
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate for intravenous paclitaxel (PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles (PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio (TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects.
ISSN:1875-5364
1875-5364
DOI:10.1016/S1875-5364(15)30097-2