Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system.
10.1016/S1875-5364(15)30097-2
- Author:
Li ZHANG
1
,
2
;
Jian-Ping ZHOU
3
;
Jing YAO
4
Author Information
1. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
2. Department of Pharmacy, Nanhu Community Health Centre, Nanjing 210019, China.
3. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: zhoujpcpu@163.com.
4. State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yaojing@cpu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Antitumor activity;
Conjugate;
Glycyrrhetinic acid;
Hyaluronic acid;
Synergistically targeted delivery
- MeSH:
Animals;
Antineoplastic Agents;
administration & dosage;
adverse effects;
chemistry;
Apoptosis;
drug effects;
Drug Carriers;
chemistry;
Drug Delivery Systems;
instrumentation;
methods;
Drug Synergism;
Female;
Glycyrrhetinic Acid;
chemistry;
Hep G2 Cells;
Humans;
Hyaluronic Acid;
chemistry;
Male;
Mice;
Paclitaxel;
administration & dosage;
adverse effects;
chemistry
- From:
Chinese Journal of Natural Medicines (English Ed.)
2015;13(12):915-924
- CountryChina
- Language:English
-
Abstract:
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.
