Fast in vitro hydrolytic degradation of polyester urethane acrylate biomaterials: Structure elucidation, separation and quantification of degradation products

Abstract

Synthetic biomaterials have evoked extensive interest for applications in the field of health care. Prior to administration to the body a quantitative study is necessary to evaluate their composition. An in vitro method was developed for the quick hydrolytic degradation of poly-2-hydroxyethyl methacrylate (pHEMA), poly(lactide-co-glycolide50/50)1550-diol (PLGA(50:50)1550-diol), PLGA(50:50)1550-diol(HEMA)2 and PLGA(50:50)1550-diol(etLDI-HEMA)2 containing ethyl ester lysine diisocyanate (etLDI) linkers using a microwave instrument. Hydrolysis time and temperature were optimized while monitoring the degree of hydrolysis by 1H NMR spectroscopy. Complete hydrolytic degradation was achieved at 120°C and 3bar pressure after 24h. Chemical structure elucidations of the degradation products were carried out using 1H and 13C NMR spectroscopy. The molecular weight (MW) of the polymethacrylic backbone was estimated via size-exclusion chromatography coupled to refractive index detection (SEC-dRI). A bimodal MW distribution was found experimentally, also in the pHEMA starting material. The number average molecular weights (Mn) of the PLGA-links (PLGA(50:50)1550-diol) were calculated by high pressure liquid chromatography–time-of-flight mass spectrometry (HPLC–TOF-MS) and 1H NMR. The amounts of the high and low MW degradation products were determined by SEC-dRI and, HPLC–TOF-MS, respectively. The main hydrolysis products poly (methacrylic acid) (PMAA), ethylene glycol (EG), diethylene glycol (DEG), lactic acid (LA), glycolic acid (GA) and lysine were recovered almost quantitatively. The current method leads to the complete hydrolytic degradation of these materials and will be helpful to study the degradation behavior of these novel cross-linked polymeric biomaterials.