In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-l-lysine and poly-l-lysine/poly-l-glutamate in rats

  • K. Isaksson
  • D. Åkerberg
  • M. Posaric-Bauden
  • R. Andersson
  • B. Tingstedt
Article
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Abstract

The combination of two differently charged polypeptides, poly-l-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague–Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

Keywords

Blood Smear Intraperitoneal Administration Bowel Anastomosis Repeat Blood Sample Endothelial Disruption 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • K. Isaksson
    • 1
    • 2
  • D. Åkerberg
    • 1
    • 2
  • M. Posaric-Bauden
    • 1
    • 2
  • R. Andersson
    • 1
    • 2
  • B. Tingstedt
    • 1
    • 2
  1. 1.Department of SurgerySkåne University Hospital in LundLundSweden
  2. 2.Department of Clinical SciencesLund UniversityLundSweden

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