New complexes of metformin based on the copolymer of N-vinylpyrrolidone with triethylene glycol dimethacrylate and their activity in experimental type 2 diabetes mellitus

The complexes of metformin (MET) and the copolymer of N-vinylpyrrolidone with triethylene glycol dimethacrylate with absolute molecular weight ca. 26 kDa and hydrodynamic radius of macromolecules about 4 nm have been prepared and studied in water buffer solution. Their sizes in neutral phosphate buffer solution depended on MET (10–40 wt%) per the copolymer content, temperature and the copolymer concentrations. Quantum chemical simulation has shown the most energetically favorable and stable structure is one with the coordination of neighboring NH2 groups of MET via oxygen carbonyl of the VP fragment. The effective binding constant of MET with the copolymer estimated from the absorption spectroscopy was found to be ~ 1.8 × 103 M−1. The MET-copolymer compositions were analyzed by IR spectroscopy, thermogravimetry, differential scanning calorimetry, and X-ray diffraction. The copolymer complex with 20 wt% of MET affected blood glucose level in streptozotocin-induced diabetic mice like MET and decreased aldose reductase activity in contrast with the drug and MET-PVP complex.