Biodegradable oligo(amidoamine/β-amino ester) hydrogels for controlled insulin delivery

An injectable biodegradable hydrogel system based on oligo(amidoamine/β-amino ester) (OAAAE) was designed and synthesized for controlled release of insulin under the physiological conditions. OAAAE was prepared in one step via the Michael-addition oligomerization of the secondary amine groups of 4,4-trimethylene dipiperidine (TMDP) with the vinyl groups of 1,8-octylene diacrylamide (ODA) and 1,6-hexane diol diacrylate (HDA). The formed oligomer was characterized by 1H NMR and gel permeation chromatography (GPC). OAAAE in aqueous solution (20 wt%) underwent a gel-sol transition in the pH range of 6.8-7.4. A complex hydrogel was formed when mixing insulin with the oligomer solution followed by increasing pH and temperature. Degradation of the hydrogel, influence of insulin on gel phase and gel strength, in vitro cytotoxicity of OAAAE, in vitro and in vivo release of insulin from the complex hydrogel were investigated. Furthermore, the in vivo release profile of insulin from the complex hydrogel was compared with that from the neutral hydrogel.