Thermosensitive Hydrogel Containing Doxycycline Exerts Inhibitory Effects on Abdominal Aortic Aneurysm Induced By Pancreatic Elastase in Mice

Abstract

Doxycycline (DOX) is reported to exert therapeutic effects against abdominal aortic aneurysm (AAA), a severe degenerative disease. In this study, a DOX hydrogel formulation of DOX/PECT^gel is studied, and its phase transition behavior and in vitro release profiles are explored. In addition, the anti-AAA effects and bioavailability of DOX/PECT^gel are evaluated in an elastase induced AAA mouse model. The results show that the phase transition temperature of 30% poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) solution is above 34 °C. In vitro release profiles of DOX/PECT^gel indicate a fast release of DOX at the first two days, followed by a slow and sustained release for 14 d. In vivo single-dose single subcutaneous injection of DOX/PECT^gel containing 8.4 or 4.2 mg mL^-1 DOX presents comparatively preventive effects on AAA, compared to intraperitoneal injections of DOX alone at a dose of 15 mg kg^-1 for seven injections, while DOX bioavailability of the DOX/PECT^gel treated groups is 1.39 times or 1.19 times of the DOX alone treated group, respectively.

Keywords: PECT; abdominal aortic aneurysm; doxycycline; thermosensitive hydrogels.