In Vitro Degradation Behavior of Microspheres Based on Cross-Linked Dextran

摘要

The aim of this study was to investigate the in vitro degradation of hydroxyl ethyl methacrylated dextran(dex-HEMA)microspheres.Dextran microspheres were incubated in phosphate buffer pH 7.4 at 37 deg C,and the dry mass,mechanical strength,and chemical composition of the microspheres were monitored in time.The amount and nature of the formed degradation products were established for microspheres with different cross-link densities by FT-IR(Fourier transformed infrared spectroscopy),NMR,mass spectrometry,SEC analysis,and XPS(X-ray photoelectron microscopy).The dex-HEMA microspheres DS 12(degree of HEMA substitution;the number of HEMA groups per 100 glucose units)incubated at pH 7.4 and 37 deg C showed a continuous mass loss,leaving after 6 months a residue of about 10%(w/w)of water-insoluble products.NMR,mass spectrometry,and SEC showed that the water-soluble degradation products consisted of dextran,low molecular weight pHEMA(M_n approx= 15 kg/mol),and small amounts of unreacted HEMA and HEMA-DMAP(intermediate reaction product of the Baylis-Hillman reaction of HEMA with DMAP(4-dimethyl aminopyridine)).Microscopy revealed that the water-insoluble residue consisted of particles with shape and size similar to that of nondegraded microspheres.However,these particles had lost their mechanical strength as evidenced from micromanipulation experiments.FT-IR and XPS(X-ray photoelectron microscopy)revealed that these particles consisted of pHEMA,of which a small fraction was soluble in methanol(M_n ranging between 27 and 82 kg/mol).The insoluble material likely consisted of lightly cross-linked pHEMA.In conclusion,in vitro degradation of dex-HEMA microspheres results in the formation of water-soluble degradation products(mainly dextran),leaving a small water-insoluble residue mainly consisting of pHEMA.