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Drug targeting using thermally responsive polymers and local hyperthermia.

Publication ,  Journal Article
Meyer, DE; Shin, BC; Kong, GA; Dewhirst, MW; Chilkoti, A
Published in: J Control Release
July 6, 2001

We report a new thermal targeting method in which a thermally responsive drug carrier selectively accumulates in a solid tumor that is maintained above physiological temperature by externally applied, focused hyperthermia. We synthesized two thermally responsive polymers that were designed to exhibit a lower critical solution temperature (LCST) transition slightly above physiological temperature: (1) a genetically engineered elastin-like polypeptide (ELP) and (2) a copolymer of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm). The delivery of systemically injected polymer-rhodamine conjugates to solid tumors was investigated by in vivo fluorescence video microscopy of ovarian tumors implanted in dorsal skin fold window chambers in nude mice, with and without local hyperthermia. When tumors were heated to 42 degrees C, the accumulation of a thermally responsive ELP with a LCST of 40 degrees C was approximately twofold greater than the concentration of the same polymer in tumors that were not heated. Similar results were also obtained for a thermally responsive poly(NIPAAM-co-AAm), though the enhanced accumulation of this carrier in heated tumors was lower than that observed for the thermally responsive ELP. These results suggest that enhanced delivery of drugs to solid tumors can be achieved by conjugation to thermally responsive polymers combined with local heating of tumors.

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Published In

J Control Release

DOI

ISSN

0168-3659

Publication Date

July 6, 2001

Volume

74

Issue

1-3

Start / End Page

213 / 224

Location

Netherlands

Related Subject Headings

  • Spectrophotometry, Ultraviolet
  • Polymers
  • Pharmacology & Pharmacy
  • Nephelometry and Turbidimetry
  • Microscopy, Video
  • Microscopy, Fluorescence
  • Mice, Nude
  • Mice
  • Hyperthermia, Induced
  • Elastin
 

Citation

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Meyer, D. E., Shin, B. C., Kong, G. A., Dewhirst, M. W., & Chilkoti, A. (2001). Drug targeting using thermally responsive polymers and local hyperthermia. J Control Release, 74(1–3), 213–224. https://doi.org/10.1016/s0168-3659(01)00319-4
Meyer, D. E., B. C. Shin, G. A. Kong, M. W. Dewhirst, and A. Chilkoti. “Drug targeting using thermally responsive polymers and local hyperthermia.J Control Release 74, no. 1–3 (July 6, 2001): 213–24. https://doi.org/10.1016/s0168-3659(01)00319-4.
Meyer DE, Shin BC, Kong GA, Dewhirst MW, Chilkoti A. Drug targeting using thermally responsive polymers and local hyperthermia. J Control Release. 2001 Jul 6;74(1–3):213–24.
Meyer, D. E., et al. “Drug targeting using thermally responsive polymers and local hyperthermia.J Control Release, vol. 74, no. 1–3, July 2001, pp. 213–24. Pubmed, doi:10.1016/s0168-3659(01)00319-4.
Meyer DE, Shin BC, Kong GA, Dewhirst MW, Chilkoti A. Drug targeting using thermally responsive polymers and local hyperthermia. J Control Release. 2001 Jul 6;74(1–3):213–224.
Journal cover image

Published In

J Control Release

DOI

ISSN

0168-3659

Publication Date

July 6, 2001

Volume

74

Issue

1-3

Start / End Page

213 / 224

Location

Netherlands

Related Subject Headings

  • Spectrophotometry, Ultraviolet
  • Polymers
  • Pharmacology & Pharmacy
  • Nephelometry and Turbidimetry
  • Microscopy, Video
  • Microscopy, Fluorescence
  • Mice, Nude
  • Mice
  • Hyperthermia, Induced
  • Elastin