Development of a Supramolecular Hydrogel for Intraperitoneal Injections.

Autor: Wintjens AGWE; Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands., Fransen PKH; UPyTher BV, Eindhoven, 5612AE, The Netherlands., Lenaerts K; Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands., Liu H; Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands., van Almen GC; UPyTher BV, Eindhoven, 5612AE, The Netherlands., van Steensel S; Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands., Gijbels MJ; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6211LK, The Netherlands.; Department of Pathology, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands.; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam University Medical Center, Amsterdam, 1081HV, The Netherlands., de Hingh IHJT; GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, 6211LK, The Netherlands.; Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, 5623EJ, The Netherlands., Dankers PYW; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, 5612AE, The Netherlands.; Department of Biomedical Engineering, Laboratory of Chemical Biology, Eindhoven University of Technology, Eindhoven, 5612AE, The Netherlands., Bouvy ND; Department of Surgery, Maastricht University Medical Center+, Maastricht, 6202AZ, The Netherlands.; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Amsterdam Infection and Immunity, Amsterdam University Medical Center, Amsterdam, 1081HV, The Netherlands.
Jazyk: angličtina
Zdroj: Macromolecular bioscience [Macromol Biosci] 2024 Jan; Vol. 24 (1), pp. e2300005. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.1002/mabi.202300005
Abstrakt: 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 is developed. To establish the optimal formulation of the hydrogel and to study its feasibility, safety, and tissue compatibility, in vitro, postmortem, and in vivo experiments are performed. In vitro tests reveal that a hydrogelator formulation with pH ≥ 9 results in a constant viscosity of 0.1 Pa·s. After administration postmortem, the hydrogel covers the parietal and visceral peritoneum with a thin, soft layer. In the subsequent in vivo experiments, 14 healthy rats are subjected to intraperitoneal injection with the hydrogel. Fourteen and 28 days after implantation, the animals are euthanized. Intraperitoneal exposure to the hydrogel is not resulted in significant weight loss or discomfort. Moreover, no macroscopic adverse effects or signs of organ damage are detected. In several intra-abdominal tissues, vacuolated macrophages are 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.
(© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.)
Databáze: MEDLINE