A novel polypeptide derived from human lactoferrin in sodium hyaluronate prevents postsurgical adhesion formation in the rat.
OBJECTIVE
The objective of the study was to evaluate whether a peptide derived from human lactoferrin, PXL01 could act safely to reduce the formation of peritoneal adhesions in the rat model and to map the molecular mechanisms of its action.


BACKGROUND
Adhesion formation is a significant problem within every surgical discipline causing suffering for the patients and major cost for the society. For many decades, attempts have been made to reduce postsurgical adhesions by reducing surgical trauma. It is now believed that major improvements in adhesion prevention will only be reached by developing dedicated antiscarring products, which are administrated in connection to the surgical intervention.


METHODS
Anti-inflammatory as well as fibrinolytic activities of PXL01 were studied in relevant human cell lines. Using the sidewall defect-cecum abrasion model in the rat, the adhesion prevention properties of PXL01 formulated in sodium hyaluronate were evaluated. Large bowel anastomosis healing model in the rat was applied to study if PXL01 would have any negative effects on intestine healing.


RESULTS
PXL01 exhibits an inhibitory effect on the most important hallmarks of scar formation by reducing infections, prohibiting inflammation, and promoting fibrinolysis. PXL01 formulated in sodium hyaluronate markedly reduced formation of peritoneal adhesions in rat without any adverse effects on wound healing.


CONCLUSIONS
A new class of synthetically derived water soluble low molecular weight peptide compound, PXL01 showed marked reduction of peritoneal adhesion formation in an animal model without any negative effects on healing. On the basis of these data, a comprehensive adhesion prevention regimen in clinical situation is expected.
Nilsson
Elin
E
PharmaSurgics AB, Gothenburg, Sweden.
Björn
Camilla
C
Sjöstrand
Veronika
V
Lindgren
Kerstin
K
Münnich
Mattias
M
Mattsby-Baltzer
Inger
I
Ivarsson
Marie-Louise
ML
Olmarker
Kjell
K
Mahlapuu
Margit
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004339:Drug Compounding; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007781:Lactoferrin; D010532:Peritoneal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011183:Postoperative Complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000517:prevention & control; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D002352:Carrier Proteins; C490098:LTF protein, human; D006820:Hyaluronic Acid; D007781:Lactoferrin