Thermosensitive hydrogel containing dexamethasone micelles for preventing postsurgical adhesion in a repeated-injury model

• Published in: Scientific reports Vol. 5; no. 1; p. 13553
• Main Authors: Wu, Qinjie, Wang, Ning, He, Tao, Shang, Jinfeng, Li, Ling, Song, Linjiang, Yang, Xi, Li, Xia, Luo, Na, Zhang, Wenli, Gong, Changyang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-09-2015; Nature Publishing Group
• Subjects: 631/154/152; 639/301/54; 692/699/1503; Abdominal Injuries - pathology; Abdominal Wall - pathology; Adhesion; Animal models; Animals; Biodegradability; Biodegradation; Cecum - injuries; Cecum - pathology; Cell Survival - drug effects; Controlled release; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - chemistry; Drug Carriers - chemistry; Drug Carriers - toxicity; Electron microscopy; Female; Humanities and Social Sciences; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - toxicity; Hydrogels; Mice; Micelles; Microscopy, Electron, Scanning; Models, Animal; multidisciplinary; Nanostructures - chemistry; Nanostructures - ultrastructure; Particle Size; Peritoneum; Phase Transition; Phase transitions; Polymers - chemistry; Rats; Rats, Sprague-Dawley; Scanning electron microscopy; Science; Steroids; Surgery; Temperature; Temperature effects; Tissue Adhesions - prevention & control
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep13553

Tissue adhesion is a common complication after surgery. In this work, a dexamethasone loaded polymeric micelles in thermosensitive hydrogel composite (Dex hydrogel) was prepared, which combined the anti-adhesion barrier with controlled release of anti-adhesion drug. Dexamethasone (Dex) was encapsulated in polymeric micelles (Dex micelles) and then the Dex micelles were loaded into biodegradable and thermosensitive hydrogel. The obtained Dex hydrogel showed a temperature-dependent sol-gel-sol phase transition behavior. The Dex hydrogel could form a non-flowing gel
in situ
upon subcutaneous injection and gradually degrade in about 20 days. In addition, Dex hydrogel was assigned for anti-adhesion studies in a more rigorous recurrent adhesion animal model. Compared with normal saline (NS) and Dex micelles group, tissue adhesions in hydrogel and Dex hydrogel group were significantly alleviated. In Dex hydrogel group, the media adhesion score is 0, which was dramatically lower than that in blank hydrogel group (2.50,
P 
< 0.001). In histopathological examination and scanning electron microscopy (SEM) analysis, an integral neo-mesothelial cell layer with microvilli on their surface was observed, which revealed that the injured parietal and visceral peritoneum were fully recovered without the concerns of adhesion formation. Our results suggested that Dex hydrogel may serve as a potential anti-adhesion candidate.