The Controlled Release and Prevention of Abdominal Adhesion of Tannic Acid and Mitomycin C-Loaded Thermosensitive Gel

Abstract

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. A single drug or physical barrier treatment does not achieve the ideal anti-adhesion effect. We developed a thermosensitive hydrogel (PPH hydrogel) consisting of poloxamer 407 (P407), poloxamer (P188), and hydroxypropyl methylcellulose (HPMC) co-blended. An injectable thermosensitive TA/MMC-PPH hydrogel was obtained by loading tannic acid (TA) with an anti-inflammatory effect and mitomycin C (MMC), which inhibits fibroblast migration or proliferation. The optimal prescriptions of PPH hydrogels with a suitable gelling time (63 s) at 37 °C was 20% (w/v) P407, 18% (w/v) P188, and 0.5% (w/v) HPMC. The scanning electron microscopy (SEM) revealed that the PPH hydrogel had a three-dimensional mesh structure, which was favorable for drug encapsulation. The PPH hydrogel had a suitable gelation temperature of 33 °C, a high gel strength, and complicated viscosity at 37 °C, according to the rheological analysis. In vitro release studies have shown that the PPH hydrogel could delay the release of TA and MMC and conform to the first-order release rate. Anti-adhesion tests performed on rats in vivo revealed that TA/MMC-PPH hydrogel significantly reduced the risk of postoperative adhesion. In conclusion, the TA/MMC-PPH hydrogel prepared in this study showed an excellent performance in both controlled drug release and anti-adhesive effects. It can be used as a protocol to prevent or reduce postoperative abdominal adhesion.