INVIVO ASSESSMENT OF SALMON-CALCITONIN SUSTAINED-RELEASE FROM BIODEGRADABLE MICROSPHERES

Biodegradable microspheres containing salmon calcitonin (sCT), a potent polypeptide hormone which inhibits bone resorption, were prepared with poly(glycolic acid) (PGA; M.W. 40,000) by a freeze drying technique. The sustained release of sCT was assessed by monitoring the hypocalcemic effect and serum sCT levels in male Wistar rats. The sCT formulations were administered subcutaneously and periodic serum samples were obtained from the femoral artery. Drug loads of 0.3, 4.5 and 7.5% were evaluated. No significant difference was seen in the duration of hypocalcemic effect with the three drug loads. At 0.3% drug load, salmon calcitonin microspheres (sCT-MS) containing 0.4, 1.2 and 3.6 U/Kg of sCT and 0.4 U/Kg free sCT were administered to rats. The hypocalcemic effect was observed for 24 h with sCT-MS compared to only 2-3 h with free sCT. At a dose level of 3.6 U/Kg body weight, serum sCT levels were sustained for over 5 days following sCT-MS administration compared to only a few hours with free sCT. Porous PGA microspheres containing sCT may be used to provide sustained serum sCT concentrations for long-term therapy.