Camptothecin-loaded films for the prevention of postsurgical adhesions

Objective and design: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. Treatment: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.