Evaluation of the protective effects of curcuminoid (curcumin and bisdemethoxycurcumin)-loaded liposomes against bone turnover in a cell-based model of osteoarthritis

Drug Des Devel Ther. 2015 Apr 20;9:2285-300. doi: 10.2147/DDDT.S78277. eCollection 2015.

Abstract

Curcumin (Cur) and bisdemethoxycurcumin (BDMC), extracted from Curcuma longa, are poorly water-soluble polyphenol compounds that have shown anti-inflammatory potential for the treatment of osteoarthritis. To increase cellular uptake of Cur and BDMC in bone tissue, soybean phosphatidylcholines were used for liposome formulation. In this study, curcuminoid (Cur and BDMC)-loaded liposomes were characterized in terms of particle size, encapsulation efficiency, liposome stability, and cellular uptake. The results show that there is about 70% entrapment efficiency of Cur and BDMC in liposomes and that particle sizes are stable after liposome formation. Both types of liposome can inhibit macrophage inflammation and osteoclast differential activities. In comparison with free drugs (Cur and BDMC), curcuminoid-loaded liposomes were less cytotoxic and expressed high cellular uptake of the drugs. Of note is that Cur-loaded liposomes can prevent liposome-dependent inhibition of osteoblast differentiation and mineralization, but BDMC-loaded liposomes could not. With interleukin (IL)-1β stimulation, curcuminoid-loaded liposomes can successfully downregulate the expression of inflammatory markers on osteoblasts, and show a high osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) ratio to prevent osteoclastogenesis. In the present study, we demonstrated that Cur and BDMC can be successfully encapsulated in liposomes and can reduce osteoclast activity and maintain osteoblast functions. Therefore, curcuminoid-loaded liposomes may slow osteoarthritis progression.

Keywords: OPG/RANKL ratio; bone turnover; curcuminoid; liposome; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Biological Availability
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Curcumin / administration & dosage
  • Curcumin / analogs & derivatives*
  • Curcumin / therapeutic use
  • Diarylheptanoids
  • Drug Compounding
  • Liposomes
  • Mice
  • Nanoparticles
  • Nitrites / chemistry
  • Osteoarthritis / drug therapy*
  • Osteoclasts / drug effects
  • Osteoclasts / enzymology
  • Particle Size

Substances

  • Diarylheptanoids
  • Liposomes
  • Nitrites
  • bis(4-hydroxycinnamoyl)methane
  • Alkaline Phosphatase
  • Curcumin