Reduction of post-surgical adhesion formation with tranilast.
BACKGROUND
Preclinical studies using the rabbit sidewall and double uterine horn models were used to assess time and dose response of tranilast delivered via subcutaneous pump, p.o., or as an intraperitoneal bolus in viscoelastic gels as well as an intraperitoneal biodegradable poly(p-dioxanone) fiber in reducing adhesions compared to vehicle controls.


METHODS
New Zealand white rabbits underwent laparotomy followed by: 1) uterine horn abrasion and peripheral devascularization or 2) cecal abrasion and sidewall deperitonealization. Tranilast treatment using various vehicles and dosages was compared to vehicle alone versus no treatment. Animals were euthanized after 7 to 21 days. Adhesion formation was assessed by two independent observers.


RESULTS
There were reductions in adhesion formation when drug was delivered topically, but oral drug alone was not effective. When tranilast was given preoperatively, oral drug added to the adhesion reduction of intraperitoneal administered drug. Tranilast in a viscoelastic carrier as well as in a biodegradable fiber was effective at reducing adhesions in the double uterine horn model. The slow release of tranilast from a biodegradable rod produced overall the best results. There were no safety issues.


CONCLUSIONS
Tranilast was effective in reducing adhesions when given in a variety of vehicles in different rabbit models of adhesion formation. Overall, the sustained intraperitoneal delivery of tranilast from biodegradable fibers was the most suitable for clinical testing.
Cooper
Kevin
K
Center for Biomaterials & Advanced Technologies, Medical Devices Group, A division of Ethicon, A Johnson & Johnson Company, Somerville, New Jersey, USA.
Young
Janel
J
Wadsworth
Scott
S
Cui
Helen
H
diZerega
Gere S
GS
Rodgers
Kathleen E
KE
D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D007813:Laparotomy; D011183:Postoperative Complications / Q000517:prevention & control*; D011817:Rabbits; D000267:Tissue Adhesions / Q000517:prevention & control*; D062367:ortho-Aminobenzoates / Q000008:administration & dosage*
D062367:ortho-Aminobenzoates; C012293:tranilast