Molecular design of biodegradable polymeric micelles for temperature-responsive drug release

Masamichi Nakayama, Teruo Okano, Takanari Miyazaki, Fukashi Kohori, Kiyotaka Sakai, Masayuki Yokoyama

    Research output: Contribution to journalArticle

    259 Citations (Scopus)

    Abstract

    We designed thermo-responsive and biodegradable polymeric micelles for an ideal drug delivery system whose target sites are where external stimuli selectively release drugs from the polymeric micelles. The thermo-responsive micelles formed from block copolymers that were composed both of a hydrophobic block and a thermo-responsive block. Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) showing a lower critical solution temperature (LCST) around 40 °C was synthesized for the thermo-responsive block, while biodegradable poly(d,l-lactide), poly(ε-caprolactone), or poly(d,l-lactide-co-ε-caprolactone) was used for the hydrophobic block. By changing both the block lengths of the poly(d,l-lactide)-containing block copolymers, physical parameters such as micelle diameter and critical micelle concentration were varied. On the other hand, the choice of the hydrophobic block was revealed to be critical in relation to both on the thermo-responsive release of the incorporated anti-cancer drug, doxorubicin, and the temperature-dependent change of the hydrophobicity of the micelles' inner core. One polymeric micelle composition successfully exhibited rapid and thermo-responsive drug release while possessing a biodegradable character.

    Original languageEnglish
    Pages (from-to)46-56
    Number of pages11
    JournalJournal of Controlled Release
    Volume115
    Issue number1
    DOIs
    Publication statusPublished - 2006 Sep 28

    Fingerprint

    Micelles
    Temperature
    Drug Delivery Systems
    Drug Liberation
    Hydrophobic and Hydrophilic Interactions
    Doxorubicin
    Pharmaceutical Preparations
    dilactide
    Neoplasms

    Keywords

    • Biodegradable polymer
    • Polymeric micelle
    • Targeting
    • Temperature
    • Thermo-response

    ASJC Scopus subject areas

    • Pharmaceutical Science

    Cite this

    Molecular design of biodegradable polymeric micelles for temperature-responsive drug release. / Nakayama, Masamichi; Okano, Teruo; Miyazaki, Takanari; Kohori, Fukashi; Sakai, Kiyotaka; Yokoyama, Masayuki.

    In: Journal of Controlled Release, Vol. 115, No. 1, 28.09.2006, p. 46-56.

    Research output: Contribution to journalArticle

    Nakayama, Masamichi ; Okano, Teruo ; Miyazaki, Takanari ; Kohori, Fukashi ; Sakai, Kiyotaka ; Yokoyama, Masayuki. / Molecular design of biodegradable polymeric micelles for temperature-responsive drug release. In: Journal of Controlled Release. 2006 ; Vol. 115, No. 1. pp. 46-56.
    @article{0f13506d9c624115b4c8338b94edc77c,
    title = "Molecular design of biodegradable polymeric micelles for temperature-responsive drug release",
    abstract = "We designed thermo-responsive and biodegradable polymeric micelles for an ideal drug delivery system whose target sites are where external stimuli selectively release drugs from the polymeric micelles. The thermo-responsive micelles formed from block copolymers that were composed both of a hydrophobic block and a thermo-responsive block. Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) showing a lower critical solution temperature (LCST) around 40 °C was synthesized for the thermo-responsive block, while biodegradable poly(d,l-lactide), poly(ε-caprolactone), or poly(d,l-lactide-co-ε-caprolactone) was used for the hydrophobic block. By changing both the block lengths of the poly(d,l-lactide)-containing block copolymers, physical parameters such as micelle diameter and critical micelle concentration were varied. On the other hand, the choice of the hydrophobic block was revealed to be critical in relation to both on the thermo-responsive release of the incorporated anti-cancer drug, doxorubicin, and the temperature-dependent change of the hydrophobicity of the micelles' inner core. One polymeric micelle composition successfully exhibited rapid and thermo-responsive drug release while possessing a biodegradable character.",
    keywords = "Biodegradable polymer, Polymeric micelle, Targeting, Temperature, Thermo-response",
    author = "Masamichi Nakayama and Teruo Okano and Takanari Miyazaki and Fukashi Kohori and Kiyotaka Sakai and Masayuki Yokoyama",
    year = "2006",
    month = "9",
    day = "28",
    doi = "10.1016/j.jconrel.2006.07.007",
    language = "English",
    volume = "115",
    pages = "46--56",
    journal = "Journal of Controlled Release",
    issn = "0168-3659",
    publisher = "Elsevier",
    number = "1",

    }

    TY - JOUR

    T1 - Molecular design of biodegradable polymeric micelles for temperature-responsive drug release

    AU - Nakayama, Masamichi

    AU - Okano, Teruo

    AU - Miyazaki, Takanari

    AU - Kohori, Fukashi

    AU - Sakai, Kiyotaka

    AU - Yokoyama, Masayuki

    PY - 2006/9/28

    Y1 - 2006/9/28

    N2 - We designed thermo-responsive and biodegradable polymeric micelles for an ideal drug delivery system whose target sites are where external stimuli selectively release drugs from the polymeric micelles. The thermo-responsive micelles formed from block copolymers that were composed both of a hydrophobic block and a thermo-responsive block. Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) showing a lower critical solution temperature (LCST) around 40 °C was synthesized for the thermo-responsive block, while biodegradable poly(d,l-lactide), poly(ε-caprolactone), or poly(d,l-lactide-co-ε-caprolactone) was used for the hydrophobic block. By changing both the block lengths of the poly(d,l-lactide)-containing block copolymers, physical parameters such as micelle diameter and critical micelle concentration were varied. On the other hand, the choice of the hydrophobic block was revealed to be critical in relation to both on the thermo-responsive release of the incorporated anti-cancer drug, doxorubicin, and the temperature-dependent change of the hydrophobicity of the micelles' inner core. One polymeric micelle composition successfully exhibited rapid and thermo-responsive drug release while possessing a biodegradable character.

    AB - We designed thermo-responsive and biodegradable polymeric micelles for an ideal drug delivery system whose target sites are where external stimuli selectively release drugs from the polymeric micelles. The thermo-responsive micelles formed from block copolymers that were composed both of a hydrophobic block and a thermo-responsive block. Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) showing a lower critical solution temperature (LCST) around 40 °C was synthesized for the thermo-responsive block, while biodegradable poly(d,l-lactide), poly(ε-caprolactone), or poly(d,l-lactide-co-ε-caprolactone) was used for the hydrophobic block. By changing both the block lengths of the poly(d,l-lactide)-containing block copolymers, physical parameters such as micelle diameter and critical micelle concentration were varied. On the other hand, the choice of the hydrophobic block was revealed to be critical in relation to both on the thermo-responsive release of the incorporated anti-cancer drug, doxorubicin, and the temperature-dependent change of the hydrophobicity of the micelles' inner core. One polymeric micelle composition successfully exhibited rapid and thermo-responsive drug release while possessing a biodegradable character.

    KW - Biodegradable polymer

    KW - Polymeric micelle

    KW - Targeting

    KW - Temperature

    KW - Thermo-response

    UR - http://www.scopus.com/inward/record.url?scp=33748870763&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=33748870763&partnerID=8YFLogxK

    U2 - 10.1016/j.jconrel.2006.07.007

    DO - 10.1016/j.jconrel.2006.07.007

    M3 - Article

    VL - 115

    SP - 46

    EP - 56

    JO - Journal of Controlled Release

    JF - Journal of Controlled Release

    SN - 0168-3659

    IS - 1

    ER -