Indomethacin Sustained-Release Anti-adhesion Membrane Composed of a Phospholipid and Polycaprolactone Blend

Abstract

Background: Postoperative peritoneal adhesions are among common challenging problems in surgery. The availability of limited efficient strategies to prevent intra-abdominal adhesion reinforces the need to explore new methods. Given the favorable prolonged drug release characteristics of polycaprolactone (PCL) films and their ability to act as a biodegradable physical barrier implant, along with the anti-inflammatory and anti-adhesion properties of indomethacin and phospholipids, this study hypothesized that indomethacin sustained-release membrane composed of phosphatidylcholine (PC) and PCL blend could efficiently prevent abdominal adhesion formation. Methods: Different polymeric and polymeric/lipidic hybrid formulations with three feeding materials to drug weight ratios were prepared, and their physicochemical characteristics and drug release kinetics were evaluated and compared. Abdominal adhesions were induced in 48 rats by the abrasion of the cecum and excision of a section of the opposite abdominal wall. Adhesion formation was evaluated by macroscopic scoring, histological, scanning electron microscopy, and polymerase chain reaction analyses. Results: Both PCL and PCL-PC films exhibited sustained indomethacin release profiles. The X-ray diffraction and Fourier-transform infrared spectroscopy studies confirmed indomethacin incorporation in formulations in molecular dispersion form without any interaction. The films showed smooth surfaces and good mechanical properties. The treatment with indomethacin PCL-PC membrane significantly reduced the expression levels of tumor necrosis factor-alpha, transforming growth factor-beta, interleukin-1, interleukin-6, and fibrinogen in the adhesion tissues. The separation of the injured peritoneum, very low adhesion scores, and complete mesothelial cell regeneration were also achieved. Conclusions: This study suggests that indomethacin-eluting PCL-PC membrane acting through the combination of physical barrier, anti-inflammatory agents, and controlled drug delivery warrants an effective approach to prevent intra-abdominal adhesion.