Control of adriamycin cytotoxic activity using thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N,N- dimethylacrylamide)-b-poly(D,L-lactide)

Fukashi Kohori, Kiyotaka Sakai, Takao Aoyagi, Masayuki Yokoyama, Masayuki Yamato, Yasuhisa Sakurai, Teruo Okano

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Adriamycin (ADR)-loaded thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(D,L-lactide) were prepared by dialysis from its dimethylacetamide solution against water. Microfiltration was successfully applied to removal of block copolymer associates, which were smaller than micellar structures. By this microfiltration polymeric micelles showing a lower critical solution temperature (LCST) at 40°C in phosphate buffered saline was obtained with a monodispersed size distribution of 69.2 nm in cumulant average diameter. ADR- loaded micelles released more ADR at 42.5°C (above the LCST) than at 37°C (below the LCST). ADR-loaded micelles did not show much cytotoxic activity against bovine aorta endothelial cells at 37°C, in contrast to high cytotoxicity at 42.5°C. On the other hand, free ADR expressed high cytotoxicity at both the incubation temperatures. Thus, thermally responsive polymeric micelles showed distinct control of ADR cytotoxic activity by temperature, while free ADR did not. From these results, an effective target therapy against solid tumors is feasible for these polymeric micelles by a combination of selective delivery to tumor sites based on stable micellar structures at 37°C and enhanced cytotoxic activity of these drug-loaded micelles at 42.5°C by local heating at tumor sites.

Original languageEnglish
Pages (from-to)195-205
Number of pages11
JournalColloids and Surfaces B: Biointerfaces
Volume16
Issue number1-4
DOIs
Publication statusPublished - 1999 Nov 1

Keywords

  • Adriamycin
  • Cytotoxicity
  • Poly(D,L-lactide)
  • Poly(N-isopropylacrylamide)
  • Polymeric micelles
  • Thermal response

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Control of adriamycin cytotoxic activity using thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N,N- dimethylacrylamide)-b-poly(D,L-lactide)'. Together they form a unique fingerprint.

  • Cite this