IN-VITRO IN-VIVO COMPARISON OF DRUG-RELEASE AND POLYMER EROSION FROM BIODEGRADABLE P(FAD-SA) POLYANHYDRIDES - A NONINVASIVE APPROACH BY THECOMBINED USE OF ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY AND NUCLEAR-MAGNETIC-RESONANCE IMAGING

Purpose. The purpose of this study was to compare drug release and pol ymer erosion from biodegradable P(FAD-SA) polyanhydrides in vitro and in vivo in real time and with minimal disturbance of the investigated system. Methods. P(FAD-SA) 20:80 and P(FAD-SA) 50:50 polymer tablets w ere loaded with the spin probe 3-carboxy-2,2,5,5-tetramethyl-pyrrollid ine-1-oxyl (PCA) and implanted subcutaneously in the neck of rats or p laced in 0.1 M phosphate buffer. 1.1 GHz EPR spectroscopy experiments and 7T MRI studies (T1 and T2 weighted) were performed. Results. A fro nt of water penetration was visible by MRI in vitro in the case of P(F AD-SA) 20:80, but not for P(FAD-SA) 50:50. For both polymers, the thic kness of the tablets decreased with time and a insoluble, easy deforma ble residue remained. Important processes such as edema, deformation o f the implant, encapsulation and bioresorption were observable by MRI in vivo. P(FAD-SA) 50:50 was almost entirely absorbed by day 44, where as an encapsulated residue was found for P(FAD-SA) 20:80 after 65 days . The EPR studies gave direct evidence of a water penetration induced changes of the microenvironment inside the tablet. EPR signals were st ill detectable in P(FAD-SA) 20:80 implants after 65 days, while the ni troxide was released in vitro within 16 days. Conclusions. Important p arameters and processes such as edema, deformation of the tablet, micr oviscosity inside the tablet and encapsulation can be monitored in rea l time by the combined use of the noninvasive techniques MRI and EPR l ending to better understanding of the differences between the in vitro and in vivo situation.