Effect of Oral Nonionic Polymeric Micelles Delivered Parathyroid Hormone cDNA on Bone Density and Microarchitecture.

ABSTRACT

INTRODUCTION: Parathyroid Hormone (PTH) is an effective therapeutic agent for osteoporosis, but the treatment requires long-term daily injections. Oral gene delivery is a less invasive alternative to daily injections. OBJECTIVE: The aim of this study is to investigate the effect of orally administered nonionic polymeric micelles of plasmid cDNA containing human cytomegalovirus promoter (PCMV)-PTH (1-34) plus EDTA on body mineral density and bone microstructure in ovariectomized rats. MATERIAL AND METHODS: A total of 27 Spraque-Dawley female rats were subjected to a bilateral ovariectomy. One month following the ovariectomy, they were randomly assigned to three groups (1) (PCMVPTH (1-34) cDNA in polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) polymeric micelle formations plus EDTA); (2) PCMV-PTH (1-34) cDNA and (3) drinking water. The treatment was administered by oral gavage on day 1, 2, 7, 14, and 21 at 8-hour intervals. Body mineral density, bone volume fraction, and trabecular thickness of the lumbar spine and femoral neck were examined with peripheral quantitative computed tomography at pre- and post-intervention (3 months after the start of the intervention) and analyzed using two-way repeated measures analysis of variance. RESULTS: Results showed that bone mineral density, bone volume fraction and trabecular thickness were significantly increased in Group 1 over time, compared with those in Group 2 and Group 3. CONCLUSION: In conclusion, significantly improved bone mineral density and bone microstructure were observed in ovariectomized rats treated with PTH (1-34) cDNA delivered by nonionic polymeric micelles.