Paclitaxel-loaded crosslinked hyaluronic acid films for the prevention of postsurgical adhesions.
OBJECTIVE
Post surgical adhesion formation results in significant morbidity for surgical patients. The purpose of this study was to investigate the use of paclitaxel (PTX) as an inhibitor of adhesion formation in rats and to design and characterize a controlled release film formulation of the drug for application to exposed surgical sites.


METHODS
The rat cecal side wall abrasion model was used to investigate the anti-adhesion properties of PTX. The drug was administered by either intraperitoneal injection (i.p.), as the cremophor formulation (Taxol) or by application of carbodiimide crosslinked hyaluronic acid (HA) films containing PTX. The HA films were also characterized by measurements of elasticity, degree of swelling in water and drug release rates.


RESULTS
Taxol administered by i.p. injection at 4 mg/kg on a daily basis for between 3 and 5 days resulted in a significant reduction in adhesion formation. All animals in the control group (n = 10) had some form of adhesion following abrasion whereas the percent of animals without adhesions significantly increased and the mean incidence of adhesion formation decreased in the three Taxol treated groups. The application of 5% PTX loaded HA films had a similar significant effect in increasing both the % of animals without adhesions and in reducing the mean incidence of adhesions.


CONCLUSIONS
Paclitaxel is an effective inhibitor of adhesion formation in rats. HA crosslinked with 2 mM water soluble carbodiimide and containing 10% glycerol and 5% PTX are flexible, mucoadhesive, biocompatible controlled release films suitable for application to surgical sites for the prevention of adhesion formation.
Jackson
John K
JK
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Skinner
Kevin C
KC
Burgess
Laurette
L
Sun
Tyler
T
Hunter
William L
WL
Burt
Helen M
HM
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003432:Cross-Linking Reagents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000267:Tissue Adhesions / Q000517:prevention & control*
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D006820:Hyaluronic Acid; D017239:Paclitaxel