Self-assembled pH-responsive MPEG-b-(PLA-co-PAE) block copolymer micelles for anticancer drug delivery.
A series of amphiphilic pH-responsive poly (ethylene glycol) methyl ether-b-(poly lactic acid-co-poly (β-amino esters)) (MPEG-b-(PLA-co-PAE)) block copolymers with different PLA/PAE ratios were designed and synthesized via a Michael-type step polymerization. The molecular structures of the copolymers were confirmed with (1)H NMR and gel permeation chromatography (GPC). These amphiphilic copolymers were shown to self-assemble into core/shell micelles in aqueous solution at low concentrations, and their critical micelle concentrations (CMC) in water were 1.2-9.5 mg/L. The pH-responsive PAE segment was insoluble at pH 7.4, but it became positively charged and soluble via protonation of amino groups at pH lower than 6.5. The average particle size and zeta potential of micelles increased from 180 nm and 15 mV to 220 nm and 40 mV, respectively, when the pH decreased from 7.4 to 5.0. Doxorubicin (DOX) was loaded into the core of these micelles with a high drug loading of 18%. The in vitro DOX release from the micelles was significantly accelerated when solution pH decreased from 7.4 to 5.0. DOX release in the first 10 h appeared to follow Fickian diffusion mechanism. Toxicity test showed that the copolymers had low toxicity whereas the DOX-loaded micelles remained high cytotoxicity for HepG2 cells. The results indicate the pH-sensitive MPEG-b-(PLA-co-PAE) micelle may be a potential hydrophobic drug delivery carrier for cancer targeting therapy with sustained release.
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, People's Republic of China.
Can Yang
CY
Zhang
You Qiang
YQ
Yang
Tu Xiong
TX
Huang
Bin
B
Zhao
Xin Dong
XD
Guo
Ju Fang
JF
Wang
Li Juan
LJ
Zhang
D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C028210:monomethoxypolyethylene glycol