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

[ Vol. 17 , Issue. 3 ]

Author(s):

Sung-Hsiung Chen, Jih-Yang Ko and Fong-Fu Chou *   Pages 228 - 234 ( 7 )

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.

Keywords:

Bone mineral density, Parathyroid hormone, Oral gene, Bone microstructure, cDNA, PCMV.

Affiliation:

Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 83301, Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 83301, Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City 83301



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