Poly(lactic-co-glycolic acid) Microspheres Containing a Recombinant Parathyroid Hormone (1-34) for Sustained Release in a Rat Model

Baskaran et al.: PLGA Microspheres for Sustained Release of rhPTH (1-34) Recombinant parathyroid hormone (1-34), the drug of choice for treating severe osteoporosis, has a short halflife 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.