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Effects of pH-sensitive chain length on release of doxorubicin from mPEG-b-PH-b-PLLA nanoparticles

Authors Liu R, He B, Li, Lai, Chang J, Tang, Gu Z

Received 21 March 2012

Accepted for publication 25 April 2012

Published 14 August 2012 Volume 2012:7 Pages 4433—4446

DOI https://doi.org/10.2147/IJN.S32053

Review by Single-blind

Peer reviewer comments 5

Rong Liu,1,2 Bin He,1 Dong Li,1 Yusi Lai,1 Jing Chang,1 James Z Tang,3 Zhongwei Gu1

1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 2Dalian Institute of Chemical Physics Chinese Academy of Sciences, Dalian, China; 3Department of Pharmacy, School of Applied Sciences, University of Wolverhampton, Wolverhampton, United Kingdom

Background: Two methoxyl poly(ethylene glycol)-poly(L-histidine)-poly(L-lactide) (mPEG-PH-PLLA) triblock copolymers with different poly(L-histidine) chain lengths were synthesized. The morphology and biocompatibility of these self-assembled nanoparticles was investigated.
Methods: Doxorubicin, an antitumor drug, was trapped in the nanoparticles to explore their drug-release behavior. The drug-loaded nanoparticles were incubated with HepG2 cells to evaluate their antitumor efficacy in vitro. The effects of poly(L-histidine) chain length on the properties, drug-release behavior, and antitumor efficiency of the nanoparticles were investigated.
Results: The nanoparticles were pH-sensitive. The mean diameters of the two types of mPEG-PH-PLLA nanoparticle were less than 200 nm when the pH values were 5.0 and 7.4. The nanoparticles were nontoxic to NIH 3T3 fibroblasts and HepG2 cells. The release of doxorubicin at pH 5.0 was much faster than that at pH 7.4. The release rate of mPEG45-PH15-PLLA82 nanoparticles was much faster than that of mPEG45-PH30-PLLA82 nanoparticles at pH 5.0.
Conclusion: The inhibition effect of mPEG45-PH15-PLLA82 nanoparticles on the growth of HepG2 cells was greater than that of mPEG45-PH30-PLLA82 nanoparticles when the concentration of encapsulated doxorubicin was less than 15 µg/mL.

Keywords: poly(ethylene glycol), poly(L-histidine), poly(L-lactide), pH sensitivity, doxorubicin, drug release, nanoparticle

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