Camptothecin-loaded films for the prevention of postsurgical adhesions.
OBJECTIVE
The purpose of this work was to investigate the local application of camptothecin (CPT), a drug with anti-inflammatory, antiproliferative and antiangiogenic properties, as an inhibitor of surgical adhesion formation in rats.


METHODS
The anti-adhesion properties of CPT were investigated using the cecal sidewall abrasion model in a total of 92 rats. An adhesion score for each animal was obtained based on the strength and extent of the adhesions. Significance was determined by Students t-test and p values less than 0.05 were considered significant.


METHODS
The drug was administered by application of carbodiimide crosslinked hyaluronic acid (HA) films containing CPT at concentrations of 0, 0.6, 2.5 and 7.5% w/w at the site of surgical injury. The HA films were characterized by in vitro measurements of drug release rates.


RESULTS
In this model the application of HA films alone, or 0, 0.6, 2.5 or 7.5% w/w CPT-loaded HA films, had a significant effect in reducing the mean strength and area of adhesions (3.8 +/- 2.7, 5.6 +/- 0.7, 1.3 +/- 0.7, 0.9 +/- 0.8, 0.7 +/- 1.0, respectively) when compared to those animals in which no film was placed (8.4 +/- 2.5). In addition, a significant difference was observed in the effect of 0.6, 2.5 and 7.5% w/w CPT-loaded films when compared to the HA or 0% CPT-loaded films (p < 0.05). No toxicity was observed in the rats following administration of these films.


CONCLUSIONS
CPT loaded films inhibited the formation of adhesions in the rat cecal sidewall abrasion model. HA crosslinked with 2 mM carbodiimide and containing 20% w/w glycerol and 0.6, 2.5 or 7.5% w/w CPT are flexible, mucoadhesive, biocompatible controlled release films that can be used to prevent adhesion formation.
ARC Pharmaceuticals Inc., University of British Columbia, 102-2386 East Mall, Vancouver BC, Canada, jcashman@arcpharma.com
J
J
Cashman
H M
HM
Burt
C
C
Springate
J
J
Gleave
J K
JK
Jackson
D000818:Animals; D001835:Body Weight; D002166:Camptothecin / Q000008:administration & dosage* / Q000494:pharmacology*; D002432:Cecum / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D004548:Elasticity; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000517:prevention & control; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D000267:Tissue Adhesions / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects
D002166:Camptothecin