Novel osteoprotective nanocochleate formulation: A dual combination therapy-codelivery system against glucocorticoid induced osteoporosis

Nanomedicine. 2020 Oct:29:102273. doi: 10.1016/j.nano.2020.102273. Epub 2020 Jul 22.

Abstract

Phosphatidylserine nanocochleates (Nanocochs) are novel delivery systems that may play a prominent osteoprotective role with their cargo, vitamin D3 (Vit-D3), against osteoporosis. Therefore, this study was conducted to characterize a Nanococh containing vitamin D3 (Nanococh-D3) and investigate its potential role in improving GIO in a rat model. Roll-shaped Nanococh-D3 particles were obtained in a size range of 320 nm with a sustained release performance. Oral Nanococh-D3 significantly increased the bioavailability of Vit-D3, enhanced bone mechanical strength, and improved osteogenic biomarkers including B-ALP, osteocalcin, Ca, and OPG in GIO rats. This formulation markedly suppressed gene expression of RANK and RANKL in treated rats. Histomorphometric analysis showed significant repairs in bone tissues and TRAP staining indicated a significant decrease in osteoclasts using Nanococh-D3 in osteoporotic rats. Nanococh alone similar to Nanococh-D3 acted better than AL as a standard anti-osteoporotic drug in the improvement of bone strength. In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.

Keywords: Combination therapy; Glucocorticoid; Nanocochleate; Osteoporosis; Phosphatidylserine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholecalciferol / chemistry
  • Cholecalciferol / pharmacology*
  • Drug Combinations
  • Drug Delivery Systems*
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / toxicity
  • Humans
  • Osteocalcin / genetics
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Osteoporosis / chemically induced
  • Osteoporosis / drug therapy*
  • Osteoporosis / pathology
  • Osteoprotegerin / genetics
  • RANK Ligand / genetics
  • Rats

Substances

  • Drug Combinations
  • Glucocorticoids
  • Osteoprotegerin
  • RANK Ligand
  • Tnfrsf11b protein, rat
  • Osteocalcin
  • Cholecalciferol