Journal
JOURNAL OF CONTROLLED RELEASE
Volume 74, Issue 1-3, Pages 213-224Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0168-3659(01)00319-4
Keywords
drug delivery; tumor; hyperthermia; thermally responsive polymer; elastin-like polypeptide; poly(N-isopropylacrylamide); lower critical solution temperature; inverse transition
Funding
- NCI NIH HHS [CA42745] Funding Source: Medline
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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 degreesC. the accumulation of a thermally responsive ELP with a LCST of 40 degreesC 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. (C) 2001 Elsevier Science BY. All rights reserved.
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