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Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice

Publication ,  Journal Article
Liu, WE; Dreher, MR; Furgeson, DY; Peixoto, KV; Yuan, H; Zalutsky, MR; Chilkoti, A
Published in: Journal Of Controlled Release
November 2006

ELPs are genetically engineered, thermally responsive polypeptides that preferentially accumulate in solid tumors subjected to focused, mild hyperthermia. In this paper, we report the biodegradation, pharmacokinetics, tumor localization, and tumor spatial distribution of C-14-labeled ELPs that were radiolabeled during their biosynthesis in Escheriehia coli. The in vitro degradation rate of a thermally responsive C-14-labeled ELP1 ([C-14] ELP1) with a molecular weight of 59.4 kDa, upon exposure to murine serum, was 2.49 wt.\%/day. The apparent in vivo degradation rate of ELP1 after intravenous injection of nude mice was 2.46 wt.\%/day and its terminal half-life was 8.7 h. The tumor accumulation and spatial distribution of intravenously administered ELP1 and a control ELP that was designed to remain soluble in heated tumors (ELP2) were examined in both heated (41.5 degrees C) and unheated tumors. ELP1 accumulated at a significantly higher concentration in heated tumors than ELP1 in unheated tumors and ELP2 in heated tumors. Quantitative autoradiography of tumor sections provided similar tumor accumulation results as the whole tumor analysis but, in addition, showed that ELP1 had a more homogeneous distribution in heated tumors and a greater concentration in the tumor center than either control treatment. (c) 2006 Elsevier B.V. All rights reserved.

Duke Scholars

Published In

Journal Of Controlled Release

ISSN

0168-3659

Publication Date

November 2006

Volume

116

Issue

2

Start / End Page

170 / 178

Related Subject Headings

  • Pharmacology & Pharmacy
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0904 Chemical Engineering
  • 0903 Biomedical Engineering
 

Citation

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Liu, W. E., Dreher, M. R., Furgeson, D. Y., Peixoto, K. V., Yuan, H., Zalutsky, M. R., & Chilkoti, A. (2006). Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice. Journal Of Controlled Release, 116(2), 170–178.
Liu, W. E., M. R. Dreher, D. Y. Furgeson, K. V. Peixoto, H. Yuan, M. R. Zalutsky, and A. Chilkoti. “Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice.” Journal Of Controlled Release 116, no. 2 (November 2006): 170–78.
Liu WE, Dreher MR, Furgeson DY, Peixoto KV, Yuan H, Zalutsky MR, et al. Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice. Journal Of Controlled Release. 2006 Nov;116(2):170–8.
Liu, W. E., et al. “Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice.” Journal Of Controlled Release, vol. 116, no. 2, Nov. 2006, pp. 170–78.
Liu WE, Dreher MR, Furgeson DY, Peixoto KV, Yuan H, Zalutsky MR, Chilkoti A. Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice. Journal Of Controlled Release. 2006 Nov;116(2):170–178.
Journal cover image

Published In

Journal Of Controlled Release

ISSN

0168-3659

Publication Date

November 2006

Volume

116

Issue

2

Start / End Page

170 / 178

Related Subject Headings

  • Pharmacology & Pharmacy
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0904 Chemical Engineering
  • 0903 Biomedical Engineering