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

    124 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

    Fingerprint

    Micelles
    Doxorubicin
    micelles
    Temperature
    Tumors
    Microfiltration
    tumors
    Cytotoxicity
    temperature
    aorta
    dialysis
    Neoplasms
    Dialysis
    Endothelial cells
    poly(lactide)
    poly(IPAAm-co-DMAAm)
    block copolymers
    Heating
    Block copolymers
    Aorta

    Keywords

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

    ASJC Scopus subject areas

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

    Cite this

    Control of adriamycin cytotoxic activity using thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N,N- dimethylacrylamide)-b-poly(D,L-lactide). / Kohori, Fukashi; Sakai, Kiyotaka; Aoyagi, Takao; Yokoyama, Masayuki; Yamato, Masayuki; Sakurai, Yasuhisa; Okano, Teruo.

    In: Colloids and Surfaces B: Biointerfaces, Vol. 16, No. 1-4, 11.1999, p. 195-205.

    Research output: Contribution to journalArticle

    Kohori, Fukashi ; Sakai, Kiyotaka ; Aoyagi, Takao ; Yokoyama, Masayuki ; Yamato, Masayuki ; Sakurai, Yasuhisa ; Okano, Teruo. / Control of adriamycin cytotoxic activity using thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N,N- dimethylacrylamide)-b-poly(D,L-lactide). In: Colloids and Surfaces B: Biointerfaces. 1999 ; Vol. 16, No. 1-4. pp. 195-205.
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    AU - Kohori, Fukashi

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    AU - Aoyagi, Takao

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    AU - Yamato, Masayuki

    AU - Sakurai, Yasuhisa

    AU - Okano, Teruo

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    N2 - 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.

    AB - 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.

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