Development of a parathyroid hormone-controlled release system as a potential surgical treatment for hypoparathyroidism.
OBJECTIVE
The aim of this study was to develop a surgically implantable controlled release delivery system for parathyroid hormone (PTH) that will maintain calcium homeostasis without the adverse side effects of long-term calcium and vitamin D replacement and can be used for the treatment of hypoparathyroidism.


METHODS
Biodegradable poly(lactide-co-glycolide) (PLGA) microspheres loaded with PTH were made using a modification of the double emulsion (water/oil/water) solvent evaporation technique. To simulate the release of PTH from microspheres after implantation in an animal, the in vitro release profile for the PTH microspheres was determined by incubating the PTH microspheres in phosphate-buffered saline, serially sampling the effluent, and determining the concentration of PTH in the effluent over time using an enzyme-linked immunosorbent assay.


RESULTS
(1) PTH was successfully incorporated into PLGA microspheres. (2) Controlled release of PTH was demonstrated in vitro over a 3-week period. (3) Release of physiological significant concentrations of PTH was achieved using this methodology.


CONCLUSIONS
Controlled release of physiological concentrations of PTH can be achieved using PLGA microsphere encapsulation.
Anthony
Tiffany
T
Department of Pediatric Surgery, Yale University School of Medicine, PO Box 802062, New Haven, CT 06520, USA.
Fong
Peter
P
Goyal
Amit
A
Saltzman
W Mark
WM
Moss
R Lawrence
RL
Breuer
Christopher
C
D001672:Biocompatible Materials / Q000008:administration & dosage; D002118:Calcium / Q000378:metabolism*; D002648:Child; D004337:Drug Carriers / Q000008:administration & dosage; D004339:Drug Compounding / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage*; D006706:Homeostasis / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D007011:Hypoparathyroidism / Q000188:drug therapy* / Q000601:surgery*; D008863:Microspheres; D010281:Parathyroid Hormone / Q000008:administration & dosage*
D001672:Biocompatible Materials; D004337:Drug Carriers; D004343:Drug Implants; D010281:Parathyroid Hormone; D002118:Calcium