Thermosensitive drug delivery system of salmon calcitonin: in vitro release, in vivo absorption, bioactivity and therapeutic efficacies.

PURPOSE

The purpose of this study was to develop a biodegradable triblock copolymer, mPEG-PLGA-mPEG-based delivery system for long-term controlled release of salmon calcitonin (sCT) after single subcutaneous injection.

METHODS

The delivery system was prepared by dissolving sCT into polymer solution. In vitro release of sCT from the delivery systems was studied in phosphate buffer saline (PBS, pH 7.4) at 37 degrees C. Stability of released sCT and sCT remaining in gel formulation was evaluated using circular dichroism, HPLC and MALDI-TOF mass spectrometry. In vivo absorption and therapeutic efficacy of sCT from the polymeric formulations were examined in female wistar rats and methylprednisolone acetate (MPA)-induced osteoporosis rat model, respectively.

RESULTS

The polymeric formulations of sCT showed long term controlled release (~20 to 40 days) of sCT in its conformationally and chemically stable form. The sCT polymeric formulations controlled the release of sCT over ~20 to 40 days and prevented MPA induced osteoporosis in vivo. The released sCT was biologically active in terms of lowering serum calcium level.

CONCLUSIONS

The triblock copolymer delivery systems controlled the release of sCT in vitro and in vivo in chemically and conformationally stable as well as biologically active and therapeutically effective form.