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Collagenase-1 injection improved tumor distribution and gene expression of cationic lipoplex.

Abstract
Elevated interstitial fluid pressure (IFP) in a tumor is a barrier to tumor accumulation of systemic delivery of nanocarriers. In this study, we investigated whether intravenous injection of type I collagenase (collagenase-1) reduced IFP in tumors and increased the accumulation and gene expression of cationic liposome/plasmid DNA complex (lipoplex) in tumors after intravenous injection into mice bearing mouse lung carcinoma LLC tumors. Collagenase-1 reduced the amount of type I collagen in the tumor, and significantly decreased IFP by 65% at 1h after injection. Therefore, collagenase-1 induced 1.5-fold higher accumulation and 2-fold higher gene expression of lipoplex in tumors after intravenous injection. These findings indicated that intravenous injection of collagenase-1 improved the accumulation of lipoplex by decreasing IFP in tumors. These results support the potential use of collagen digestion as a strategy to improve systemic gene delivery into tumors.
AuthorsMako Kato, Yoshiyuki Hattori, Manami Kubo, Yoshie Maitani
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 423 Issue 2 Pg. 428-34 (Feb 28 2012) ISSN: 1873-3476 [Electronic] Netherlands
PMID22197775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Collagen Type I
  • DNA
  • Luciferases, Firefly
  • Collagenases
  • collagenase 1
  • Microbial Collagenase
Topics
  • Animals
  • Carcinoma, Lewis Lung (genetics, metabolism, therapy)
  • Cell Line, Tumor
  • Clostridium histolyticum (enzymology)
  • Collagen Type I (metabolism)
  • Collagenases (administration & dosage, isolation & purification)
  • DNA (chemistry, metabolism)
  • Extracellular Fluid (metabolism)
  • Female
  • Genetic Therapy
  • Injections, Intravenous
  • Luciferases, Firefly (biosynthesis, genetics)
  • Mice
  • Mice, Inbred C57BL
  • Microbial Collagenase (administration & dosage, isolation & purification)
  • Pressure
  • Time Factors
  • Tissue Distribution
  • Transfection (methods)

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