Preparation and characterization of insulin-loaded injectable hydrogels as potential adjunctive periodontal treatment

Abstract

The application of local drugs as adjunctive periodontal treatment is a topic of rapidly increasing interest. Consequently, new discoveries are arising, a noteworthy portion of which employ hydrogels as delivery systems due to their high biocompatibility with and similarity to human tissues. In the search for new therapeutic agents capable of aiding periodontal treatment, authors became interested in a unique concept investigated by very few in vitro or in vivo studies concerning the local application of insulin. These studies concluded that insulin promotes the recovery and regeneration of damaged soft and bone tissues. The aim of the study was an endeavor to design a linear hydrogel that is injectable into periodontal pockets, and is able to carry a small insulin load through physical bonds and provide sustained release. The chitosan hydrogel as well as blends of polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) and polyethylene glycol (PEG) were prepared and characterized in terms of the hydrogel texture and injectability. Afterward, to study the insulin release kinetics, a specific amount of each formulation was loaded with insulin, and then incubated in phosphate-buffered saline (PBS). Specimens of the incubated samples were withdrawn daily to measure insulin concentrations by means of the ultraviolet (UV)-absorbance method; ultimately the cumulative release was calculated. Out of the 5 formulations, 4 had homogenous one-phasic texture and their insulin release profiles in vitro ranged from a few hours to about 2 weeks. The blend of 26.5 wt% PVP, 6.6 wt% PVA, 0.03 wt% calcium chloride dihydrate (CaCl2.2H2O), and 66.8 wt% water, loaded with 2 IU/g of insulin, had favorable regular sustained release, approaching 13 days. The composition of the hydrogel, the component ratio and the amount of loaded insulin were found to affect the release profile. A linear hydrogel of copolymerized PVP, PVA and CaCl2.2H2O can serve as a local vehicle for the sustained delivery of insulin inside periodontal pockets.