title: Development of PTH eluting microspheres for the treatment of hypoparathyroidism.
abstract: BACKGROUND
  Parathyroid hormone (PTH) replacement has been demonstrated to be superior to conventional treatment with calcium supplementation and vitamin D analogs for the treatment of hypoparathyroidism. In this investigation we evaluated the feasibility of using PTH microsphere encapsulation as a potential delivery system for PTH.
  
  
  METHODS
  Using the spontaneous emulsion technique, PTH microspheres were created by encapsulating PTH (1-34) in a copolymer of polyglycolic and polylactic acid (PLGA). Additional microspheres were constructed by coencapsulating calmodulin with PTH (1-34) in the PLGA microspheres. Microsphere production was confirmed using electron microscopy. PTH release was measured in vitro using an enzyme-linked immunosorbent assay. The bioactivity of PTH released from the microspheres was confirmed in vivo using a hypoparathyroid rat model by measuring serum calcium concentrations before and 3 h after subcutaneous injection of PTH microspheres.
  
  
  RESULTS
  PTH microsphere and PTH/calmodulin microspheres could be created using the spontaneous emulsion technique. Physiologically significant PTH release was measured in vitro for 20 days. PTH release was calcium sensitive and exhibited negative feedback. This effect was augmented by coencapsulation with calmodulin. PTH released from the microspheres caused a significant rise in serum calcium levels from an average of 6.35 (6.19-6.48 mg/dL) to 8.55 mg/dL (8.22-8.73). PTH released from the PTH/calmodulin microspheres resulted in an increase in serum calcium from a mean of 6.8 (6.7-6.9 mg/dL) to 8.1 mg/dL (7.8-8.2).
  
  
  CONCLUSIONS
  The PLGA microspheres can be used to provide calcium sensitive controlled release of biologically active PTH and offer a potential mean of providing biomimetic hormone replacement therapy.
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Fong
authors.forename: Amit
authors.initials: A
authors.lastname: Goyal
authors.forename: Matthew
authors.initials: M
authors.lastname: Brennan
authors.forename: Jason
authors.initials: J
authors.lastname: Park
authors.forename: Lawrence
authors.initials: L
authors.lastname: Moss
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D002147:Calmodulin / Q000494:pharmacology*; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D025461:Feedback, Physiological / Q000187:drug effects; D020249:Hormone Replacement Therapy / Q000379:methods*; D007011:Hypoparathyroidism / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D019344:Lactic Acid; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011091:Polyesters; D011100:Polyglycolic Acid; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002147:Calmodulin; D010281:Parathyroid Hormone; D011091:Polyesters; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D002118:Calcium