Development of a Supramolecular Hydrogel for Intraperitoneal Injections.

Local intraperitoneal drug administration is considered a challenging drug delivery route. The therapeutic efficiency is low, mainly due to rapid clearance of drugs. To increase the intraperitoneal retention time of specific drugs, a pH-sensitive supramolecular hydrogel that can act as a drug delivery vehicle has been developed. To establish the optimal formulation of the hydrogel and to study its feasibility, safety, and tissue compatibility, in vitro, post-mortem, and in vivo experiments were performed. In vitro tests revealed that a hydrogelator formulation with pH ≥ 9 resulted in a constant viscosity of 0.1 Pa·s. After administration post-mortem, the hydrogel covered the parietal and visceral peritoneum with a thin, soft layer. In the subsequent in vivo experiments, 14 healthy rats were subjected to intraperitoneal injection with the hydrogel. Fourteen and 28 days after implantation, the animals were euthanized. Intraperitoneal exposure to the hydrogel did not result in significant weight loss or discomfort. Moreover, no macroscopic adverse effects or signs of organ damage were detected. In several intra-abdominal tissues, vacuolated macrophages were found indicating a physiological degradation of the synthetic hydrogel. This study demonstrates that the supramolecular hydrogel is safe for intraperitoneal application and that the hydrogel shows good tissue compatibility in rats. This article is protected by copyright. All rights reserved.