A novel Diclofenac-carrier for local treatment of osteoarthritis applying live-animal MRI

Inbar Elron-Gross, Yifat Glucksam, Inbal E. Biton, Rimona Margalit*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The prevailing chronic treatment for osteoarthritis - oral administration of NSAIDs - is accompanied by severe adverse effects and risks of gastrointestinal (GI) toxicity. The working hypothesis of this study was that increased NSAID-efficacy and alleviation of adverse effects can be achieved by local administration of a new slow-release NSAID-carrier formulation. Diclofenac was the test NSAID and collagomers - novel vesicular-shaped microparticles based on collagen-lipid conjugates - were the carriers. Collagomers were stable in simulated synovial fluid and showed: high-efficiency drug encapsulation (85%); slow drug release (τ1/2 = 11 days); high affinity to target cells (Kd = 2.6 nM collagen). In vitro activity of Diclofenac released from the carriers was similar to fresh drug solutions. Diclofenac-collagomer therapeutic effects were studied in osteoarthritis-induced rats, using live-animal MRI. A single intra-articular injection of the Diclofenac-collagomer formulation reduced inflammation over 3 weeks significantly vs. untreated animals (p < 0.001), and vs. the conventional treatment which is free drug PerOs (p < 0.03). Bypassing the GI, the novel treatment circumvents adverse effects of the conventional approach. In conclusion, the collagomers performed as functional Diclofenac-depots for local treatment of osteoarthritis, avoiding GI adverse effects. The in vivo results merit further investigations of this novel NSAID formulation as a valid option to the conventional treatment.

Original languageEnglish
Pages (from-to)65-70
Number of pages6
JournalJournal of Controlled Release
Volume135
Issue number1
DOIs
StatePublished - 2 Apr 2009

Keywords

  • Drug-carrier
  • Local administration
  • MRI
  • NSAIDs
  • Osteoarthritis

Fingerprint

Dive into the research topics of 'A novel Diclofenac-carrier for local treatment of osteoarthritis applying live-animal MRI'. Together they form a unique fingerprint.

Cite this