Hyaluronate – parathyroid hormone peptide conjugate for transdermal treatment of osteoporosis

Abstract

Human parathyroid hormone 1–34 fragment (PTH_1–34) has been used as a FDA-approved therapeutics to treat osteoporosis by daily subcutaneous injection. In this work, we successfully developed PTH_1–34 conjugated hyaluronic acid (HA) for the transdermal treatment of osteoporosis with improved patient compliance. HA-PTH_1–34 conjugate was synthesized by the coupling reaction between aldehyde group introduced to HA and amine group of PTH_1–34. After characterization by gel permeation chromatography (GPC) and ELISA, the biological effect of HA-PTH_1–34 conjugate on the proliferation of human osteoblast cells was confirmed by in vitro calcium colorimetric assay and cAMP assay. Two-photon microscopy clearly visualized the effective skin penetration of FITC modified HA-PTH_1–34 conjugate. The transdermally delivered HA-PTH_1–34 conjugates elevated the blood calcium concentration for more than 2 days, reflecting the feasibility for the treatment of osteoporosis.

Keywords:

• Human parathyroid hormone
• hyaluronic acid
• transdermal delivery
• osteoporosis

Acknowledgements

We thank Gyu Seop Jo for the analysis with two-photon microscopy.