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

Publication ,  Journal Article
Liu, W; Dreher, MR; Furgeson, DY; Peixoto, KV; Yuan, H; Zalutsky, MR; Chilkoti, A
Published in: J Control Release
November 28, 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 (14)C-labeled ELPs that were radiolabeled during their biosynthesis in Escheriehia coli. The in vitro degradation rate of a thermally responsive (14)C-labeled ELP1 ([(14)C] 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.

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Published In

J Control Release

DOI

ISSN

0168-3659

Publication Date

November 28, 2006

Volume

116

Issue

2

Start / End Page

170 / 178

Location

Netherlands

Related Subject Headings

  • Time Factors
  • Recombinant Proteins
  • Pharmacology & Pharmacy
  • Peptides
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Hyperthermia, Induced
  • Humans
  • Half-Life
 

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Liu, W., 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. J Control Release, 116(2), 170–178. https://doi.org/10.1016/j.jconrel.2006.06.026
Liu, Wenge, Matthew R. Dreher, Darin Y. Furgeson, Katia V. Peixoto, Hong Yuan, Michael R. Zalutsky, and Ashutosh Chilkoti. “Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice.J Control Release 116, no. 2 (November 28, 2006): 170–78. https://doi.org/10.1016/j.jconrel.2006.06.026.
Liu W, Dreher MR, Furgeson DY, Peixoto KV, Yuan H, Zalutsky MR, et al. Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice. J Control Release. 2006 Nov 28;116(2):170–8.
Liu, Wenge, et al. “Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice.J Control Release, vol. 116, no. 2, Nov. 2006, pp. 170–78. Pubmed, doi:10.1016/j.jconrel.2006.06.026.
Liu W, Dreher MR, Furgeson DY, Peixoto KV, Yuan H, Zalutsky MR, Chilkoti A. Tumor accumulation, degradation and pharmacokinetics of elastin-like polypeptides in nude mice. J Control Release. 2006 Nov 28;116(2):170–178.
Journal cover image

Published In

J Control Release

DOI

ISSN

0168-3659

Publication Date

November 28, 2006

Volume

116

Issue

2

Start / End Page

170 / 178

Location

Netherlands

Related Subject Headings

  • Time Factors
  • Recombinant Proteins
  • Pharmacology & Pharmacy
  • Peptides
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Hyperthermia, Induced
  • Humans
  • Half-Life