Controlled Release of Parathyroid Hormone as a Potential Treatment of Hypoparathyroidism
Amit Goyal1, Tiffany L Anthony1, Peter Fong2, W. Mark Saltzman2, Christopher Breuer1
1Yale University School of Medicine, New Haven, CT;2Department of Biomedical Engineering, Yale University, New Haven, CT
Objective:
To develop controlled release delivery system for parathyroid hormone (PTH) that can maintain calcium homeostasis without adverse side effects of long term calcium and vitamin D replacements.
Design:
Experimental Animal Model
Setting:
Most common cause of hypoparathyroidism is iatrogenic injury to parathyroid glands during thyroid resection. Estimates of transient hypoparathyroidism range between 6.9% and 46%. Estimates of permanent hypoparathyroidism range between 0.4% and 33%. Our drug delivery system will benefit these patients.
Other Participants:
Parathyroidectomized Sprague-Dawley rats.
Interventions: Biodegradable poly(Lactide-co-Glycolide) (PLGA) microspheres loaded with PTH (1-34) were made using double emulsion solvent evaporation technique. In vitro release profile for PTH microspheres was determined by incubating PTH microspheres in phosphate buffered saline using an enzyme-linked immunosorbent assay. To confirm bioactivity, in vivo studies with these microspheres were carried out using a surgically created hypoparathyroid rat model and serial serum calcium measurements.
Main Outcome Measures:
(1) PTH 1-34 levels in vitro (2) serum calcium levels in vivo.
Results:
(1) PTH was successfully incorporated into PLGA microspheres. (2) Controlled release of 8000 pcg of PTH was demonstrated in vitro over a 3 week period. (3) Bioactivity of PTH released from microspheres was demonstrated by elevation of serum calcium in the animal model. In hypoparathyroid rats (n=3) baseline calcium (5.85 mg/dl) increased by 2.34 ± 0.27 mg/dl or 40%. (4) Calcium homeostasis was maintained for up to five days after a single subcutaneous injection of these microspheres.
Conclusions:
Controlled release of physiological concentrations of bioactive PTH can be achieved using PLGA microspheres.
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