NONINVASIVE MEASUREMENT OF PROTEIN RELEASE FROM SUBCUTANEOUS DEPO FORMULATIONS IN-VIVO USING X-RAY-FLUORESCENCE

The feasibility of using radioisotope-induced X-ray fluorescence (XRF) as a noninvasive method to measure the release rate of peptides/proteins from hydrogels or other formulations in vivo following subcutaneous administration has been demonstrated. A sodium phosphate buffer solution (PBS) containing 52 mg/ml of iodinated bovine serum albumin (I-BSA) was administered subcutaneously in female Sprague-Dawley rats and the administration site was fluoresced at regular intervals over a 24-96 h period. The variation in the iodine X-ray yield with time indicated that the disappearance of I-BSA alone followed first order kinetics with a half-life of approximately 6.6 h. When the I-BSA was formulated into a polymeric hydrogel of poly( acrylic acid) (Carbopol-940), a significant increase in the half-life was observed. As the Carbopol concentration was increased from 5.61 to 18.75 mg/ml, the disappearance half-life increased from 6.3 to 14.0 h. Free iodide loaded into the Carbopol gel at equivalent concentrations had a disappearance half-life of 13.8 min.