title: A novel Diclofenac-carrier for local treatment of osteoarthritis applying live-animal MRI.
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 (tau((1/2))=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.
authors.affiliation: Department of Biochemistry, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Inbar
authors.initials: I
authors.lastname: Elron-Gross
authors.forename: Yifat
authors.initials: Y
authors.lastname: Glucksam
authors.forename: Inbal E
authors.initials: IE
authors.lastname: Biton
authors.forename: Rimona
authors.initials: R
authors.lastname: Margalit
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D024042:Collagen Type I / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D010003:Osteoarthritis / Q000175:diagnosis / Q000188:drug therapy*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010714:Phosphatidylethanolamines; D004008:Diclofenac; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine