A novel dexamethasone-loaded liposome alleviates rheumatoid arthritis in rats

Int J Pharm. 2018 Apr 5;540(1-2):57-64. doi: 10.1016/j.ijpharm.2018.02.001. Epub 2018 Feb 2.

Abstract

In this study, an inflammation-targeted delivery system based on a liposomal carrier was developed to deliver hydrophobic dexamethasone against arthritis. Using two FDA-approved excipients for intravenous injection, dexamethasone loaded liposome (Dex-Lip) was prepared by a thin-film hydration method. The biodistribution of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine-loaded liposomes (DiD-Lips) were performed in rats with adjuvant-induced arthritis and demonstrated specific targeting efficacy in the disease site. DiD-Lips showed prolonged retention time in the inflammatory joint tissues compared with free DiD. Dex-Lips effectively suppressed the joint swelling in arthritis rats and significantly down-regulated serum pro-inflammatory cytokines including tumor necrosis factor-α and interleukin-1β when compared to free dexamethasone. Furthermore, Dex-Lips had no significantly impact on the body weight, alleviated the hyperglycemia and improved haematological profiles of rheumatoid arthritis rats during the treatment process. Taken together, a safe liposomal delivery system was developed to achieve inflammation targeted therapy against arthritis.

Keywords: Biodistribution; Clinical application; Dexamethasone; Moderate toxic effects; Novel liposome; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacokinetics
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Dexamethasone / administration & dosage*
  • Dexamethasone / chemistry
  • Dexamethasone / pharmacokinetics
  • Drug Compounding
  • Freund's Adjuvant
  • Inflammation Mediators / blood
  • Injections, Intravenous
  • Interleukin-1beta / blood
  • Joints / drug effects*
  • Joints / metabolism
  • Joints / pathology
  • Lipids / chemistry*
  • Liposomes
  • Male
  • Rats, Sprague-Dawley
  • Technology, Pharmaceutical / methods
  • Tissue Distribution
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antirheumatic Agents
  • IL1B protein, rat
  • Inflammation Mediators
  • Interleukin-1beta
  • Lipids
  • Liposomes
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • Freund's Adjuvant