Tumoral acidic extracellular pH targeting of pH-responsive MPEG-poly(beta-amino ester) block copolymer micelles for cancer therapy.

Abstract

The main objective of this study was to develop and characterize a pH-responsive and biodegradable polymeric micelle as a tumor-targeting drug delivery system. The pH-responsive block copolymer was synthesized by a Michael-type step polymerization of hydrophilic methyl ether poly(ethylene glycol) (MPEG) and pH-responsive and biodegradable poly(beta-amino ester), resulting in an amphiphilic MPEG-poly(beta-amino ester) block copolymer. This copolymer, which formed nano-sized self-assembled micelles under aqueous conditions, could be efficiently (74.5%) loaded with doxorubicin (DOX) using a solvent evaporation method. In an in vitro drug release study, these DOX-loaded polymeric micelles showed noticeable pH-dependent micellization-demicellization behavior, with rapid release of DOX from the micelles in weakly acidic environments (pH 6.4) but very slow release under physiological conditions (pH 7.4). Moreover, due to demicellization, the tumor cell uptake of DOX released from polymeric micelles was much higher at pH 6.4 than at pH 7.4. When in vivo anti-tumor activity of pH-responsive polymeric micelles was evaluated by injecting the DOX-loaded polymeric micelles into B16F10 tumor-bearing mice, these micelles notably suppressed tumor growth and also prolonged survival of the tumor-bearing mice, compared with mice treated with free DOX.

• Authors: Jinyoung Ko, Kyeongsoon Park, Yoo-Shin Kim, Min Sang Kim, Jong Kwon Han, Kwangmeyung Kim, Rang-Woon Park, In-San Kim, Hyun Kyu Song, Doo Sung Lee, Ick Chan Kwon
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 123 Issue 2 Pg. 109-15 (Nov 06 2007) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 17894942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Delayed-Action Preparations
• Drug Carriers
• Esters
• Micelles
• Polymers
• poly(beta-amino ester)
• Polyethylene Glycols
• Doxorubicin
• monomethoxypolyethylene glycol

Topics

• Animals
• Antibiotics, Antineoplastic (chemistry, metabolism, pharmacology, therapeutic use)
• Cell Line, Tumor
• Chemistry, Pharmaceutical
• Delayed-Action Preparations
• Doxorubicin (chemistry, metabolism, pharmacology, therapeutic use)
• Drug Carriers
• Drug Compounding
• Esters (chemistry)
• Hydrogen-Ion Concentration
• Kinetics
• Male
• Melanoma, Experimental (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Micelles
• Nanoparticles
• Particle Size
• Polyethylene Glycols (chemistry)
• Polymers (chemistry)
• Solubility
• Technology, Pharmaceutical (methods)