Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin

Jong Oh Kim, Alexander V. Kabanov, Tatiana K Bronich

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w%) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalJournal of Controlled Release
Volume138
Issue number3
DOIs
StatePublished - Sep 15 2009

Fingerprint

Micelles
Doxorubicin
Polymers
Pharmaceutical Preparations
polyanions
Anthracyclines
Divalent Cations
Static Electricity
Metals
Carcinoma

Keywords

  • Block copolymer micelles
  • Core-shell morphology
  • Doxorubicin
  • Self-assembly

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin. / Kim, Jong Oh; Kabanov, Alexander V.; Bronich, Tatiana K.

In: Journal of Controlled Release, Vol. 138, No. 3, 15.09.2009, p. 197-204.

Research output: Contribution to journalArticle

@article{46dadf05199f497a9fc61e835c63377d,
title = "Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin",
abstract = "Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w{\%}) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX.",
keywords = "Block copolymer micelles, Core-shell morphology, Doxorubicin, Self-assembly",
author = "Kim, {Jong Oh} and Kabanov, {Alexander V.} and Bronich, {Tatiana K}",
year = "2009",
month = "9",
day = "15",
doi = "10.1016/j.jconrel.2009.04.019",
language = "English (US)",
volume = "138",
pages = "197--204",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin

AU - Kim, Jong Oh

AU - Kabanov, Alexander V.

AU - Bronich, Tatiana K

PY - 2009/9/15

Y1 - 2009/9/15

N2 - Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w%) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX.

AB - Polymer micelles with cross-linked ionic cores were prepared by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) copolymer and divalent metal cations as templates. Doxorubicin (DOX), an anthracycline anticancer drug, was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. A substantial drug loading level (up to 50 w/w%) was achieved and it was strongly dependent on the structure of the cross-linked micelles and pH. The drug-loaded micelles were stable in aqueous dispersions exhibiting no aggregation or precipitation for a prolonged period of time. The DOX-loaded polymer micelles exhibited noticeable pH-sensitive behavior with accelerated release of DOX in acidic environment due to the protonation of carboxylic groups in the cores of the micelles. The attempt to protect the DOX-loaded core with the polycationic substances resulted in the decrease of loading efficacy and had a slight effect on the release characteristics of the micelles. The DOX-loaded polymer micelles exhibited a potent cytotoxicity against human A2780 ovarian carcinoma cells. These results point to a potential of novel polymer micelles with cross-linked ionic cores to be attractive carriers for the delivery of DOX.

KW - Block copolymer micelles

KW - Core-shell morphology

KW - Doxorubicin

KW - Self-assembly

UR - http://www.scopus.com/inward/record.url?scp=68749103243&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68749103243&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2009.04.019

DO - 10.1016/j.jconrel.2009.04.019

M3 - Article

C2 - 19386272

AN - SCOPUS:68749103243

VL - 138

SP - 197

EP - 204

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 3

ER -