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pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combretastatin A4 for the combination therapy against hepatocellular carcinoma

Paper ID Volume ID Publish Year Pages File Format Full-Text
6340 484 2013 10 PDF Available
Title
pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combretastatin A4 for the combination therapy against hepatocellular carcinoma
Abstract

This study designs a pH-sensitive nanoparticle carrier of methotrexate (MTX) and combretastatin A4 (CA4) based on pullulan for the combination therapy against hepatocellular carcinoma (HCC). Briefly, N-urocanyl pullulan (URPA) with the degree of substitution (DS) of 5.2% was synthesized and then conjugated with MTX to form MTX-URPA, in which MTX content was 17.8%. MTX-URPA nanoparticles prepared by the dialysis method had spherical shape and the mean size of 187.1 nm, and showed high affinity for HepG2 cells. CA4 was successfully loaded into MTX-URPA nanoparticles and exhibited pH-sensitive in vitro release property. After intravenous injection to PLC/PRF/5-bearing nude mice, CA4 loaded MTX-URPA (CA4/MTX-URPA) nanoparticles achieved the enhanced antitumor and anti-angiogenic effects, the prolonged circulation time in blood, and the increased distributions both in the liver and the tumor. In conclusion, this drug carrier system has significant liver-targeting property and exhibits advantages for the combination therapy against hepatocellular carcinoma.

Keywords
Pullulan; Nanoparticle carrier; Targeting; Combination therapy
First Page Preview
pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combretastatin A4 for the combination therapy against hepatocellular carcinoma
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 29, September 2013, Pages 7181–7190
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering