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

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.

A sustained release formulation of doxycycline (DOX) is prepared based on poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (PECT) hydrogel (DOX/PECT^gel). DOX release from the DOX/PECT^gel is dose-dependent and can last for 14 d. One single s.c. injection of the DOX/PECT^gel exhibits significant anti-abdominal aortic aneurysm effects, which is as efficient as seven i.p. injections of DOX alone at an equal dose.

http://ift.tt/2wOUiXR