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.

MATERIALS AND 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: Peter Fong, Amit Goyal, Matthew Brennan, Jason Park, Lawrence Moss, W Mark Saltzman, Christopher K Breuer
• Journal: The Journal of surgical research (J Surg Res) Vol. 143 Issue 2 Pg. 195-9 (Dec 2007) ISSN: 0022-4804 [Print] United States
• PMID: 17720197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin
• Parathyroid Hormone
• Polyesters
• Polymers
• Polyglycolic Acid
• Lactic Acid
• poly(lactide)
• Calcium

Topics

• Animals
• Calcium (blood)
• Calmodulin (pharmacology)
• Drug Compounding
• Drug Delivery Systems (methods)
• Feedback, Physiological (drug effects)
• Hormone Replacement Therapy (methods)
• Hypoparathyroidism (drug therapy)
• Injections, Subcutaneous
• Lactic Acid
• Male
• Microscopy, Electron, Scanning
• Microspheres
• Parathyroid Hormone (pharmacology)
• Polyesters
• Polyglycolic Acid
• Polymers
• Rats
• Rats, Sprague-Dawley