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Development and Characterization of Parathyroid Hormone Microspheres for the Treatment of Hypoparathyroidism
Peter Fong, Osama Abdelghany, W. Mark Saltzman, Robert Udelsman, Christopher K Breuer
Yale University School of Medicine, New Haven, CT
Objective: The purpose of this study is to describe the fabrication and characterization of parathyroid hormone (PTH) poly(lactide-co-glycolide) microspheres for use in humans.
Design: Experimental study.
Setting: University teaching hospital.
Patients: None
Interventions: PTH microspheres were prepared by spontaneous emulsion. Microsphere production was confirmed and characterized using scanning electron microscopy. PTH release profile was constructed by incubating the microspheres in PBS, sampling the effluent at predetermined times and quantifying PTH concentration by ELISA. The biological activity of PTH was confirmed using a c-AMP immunoassay. Sterility was determined by aerobic and anaerobic cultures and pyrogenicity by limulus amebocyte lysate test. The stability of the PTH microspheres after 2 weeks storage was determined by HPLC analysis of released PTH.
Main Outcome Measure: The amount, duration, and biological activity of PTH released from the microspheres were measured and their morphology, sterility, pyrogenicity, and stability were determined.
Results: Sterile, nonpyrogenic microspheres (mean diameter of 2μm) were created. 10 mg aliquot of PTH microspheres resulted in the release of 70 μg of PTH 1-34 within a 24-hour period. The biological activity of the PTH (1-34) released from the microspheres was confirmed using the c-AMP immunoassay. Microspheres remained stable when refrigerated for up to 14 days.
Conclusions: Using spontaneous emulsion we can construct sterile, nonpyrogenic PTH microspheres to provide sustained, controlled-release of biologically active PTH. Based on these data, a phase 1 clinical trial evaluating the safety of using PTH microspheres for the treatment of patients with hypoparathyroidism is scheduled.
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