Thermosensitive Hydrogel Containing Doxycycline Exerts Inhibitory Effects on Abdominal Aortic Aneurysm Induced By Pancreatic Elastase in Mice. Issue 22 (8th September 2017)

• Record Type: Journal Article
• Authors: Yu, Maomao; Dong, Anjie; Chen, Cong; Xu, Shuxin; Cao, Yini; Liu, Shu; Zhang, Qiang; Qi, Rong
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 22(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-09-08
• Subjects: abdominal aortic aneurysm -- doxycycline -- PECT -- thermosensitive hydrogels; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201700671
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : 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.