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

Isaksson, Karolin LU ; Åkerberg, Daniel LU ; Bauden, Monika LU ; Andersson, Roland LU and Tingstedt, Bobby LU (2014) In Journal of Materials Science: Materials in Medicine 25(5). p.1293-1299
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Materials Science: Materials in Medicine
volume
25
issue
5
pages
1293 - 1299
publisher
Kluwer
external identifiers
  • pmid:24449025
  • wos:000334503300009
  • scopus:84921930099
ISSN
1573-4838
DOI
10.1007/s10856-014-5151-2
language
English
LU publication?
yes
id
647721b4-3ac3-4e9e-be7b-0e7a146d33f8 (old id 4290901)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24449025?dopt=Abstract
date added to LUP
2014-02-07 14:43:46
date last changed
2017-11-05 03:14:59
@article{647721b4-3ac3-4e9e-be7b-0e7a146d33f8,
  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.},
  author       = {Isaksson, Karolin and Åkerberg, Daniel and Bauden, Monika and Andersson, Roland and Tingstedt, Bobby},
  issn         = {1573-4838},
  language     = {eng},
  number       = {5},
  pages        = {1293--1299},
  publisher    = {Kluwer},
  series       = {Journal of Materials Science: Materials in Medicine},
  title        = {In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.},
  url          = {http://dx.doi.org/10.1007/s10856-014-5151-2},
  volume       = {25},
  year         = {2014},
}