Abstract

Recombinant parathyroid hormone (1-34), the drug of choice for treating severe osteoporosis, has a short half-life and requires daily subcutaneous injections. Controlled release formulation of recombinant parathyroid hormone (1-34) might prevent daily injections and improve therapeutic outcome. In this study, recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion method were prepared. Scanning electron microscopy proved that the microspheres were spherical in shape with 2.0 to 5.0 µm diameter. A loading efficiency up to 84 % was achieved in the optimized formulation. Release study performed using microspheres of 10:1.0 polymer:drug ratio formulation revealed that the release of recombinant parathyroid hormone (1-34) was controlled over 22 days in a biphasic manner with an initial burst and a subsequent slow release. For pharmacokinetic study, recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres were subcutaneously injected to rats at 0.01 mg/kg dose of recombinant parathyroid hormone (1-34). Plasma drug concentration of recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres were maintained for a week whereas free recombinant parathyroid hormone (1-34) was quickly eliminated within a day. These results suggest that recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres appear to have the potential for further clinical development.