Session Information
Session Type: Poster Session B
Session Time: 10:30AM-12:30PM
Background/Purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease of synovial joints, and it affects over 1 per cent of the population worldwide. Uncontrolled or inadequately treated RA can result in joint damage and disability. Despite the availability of several drugs, including the biologics, the long-term use of these drugs is frequently associated with many adverse reactions. This is partly because of widespread distribution of systemically administered drugs, exposing otherwise healthy organs to the drugs intended to suppress joint inflammation. Thus, new drug delivery modalities are needed to overcome these limitations. We described here the use of a peptide ligand to enhance the efficacy of a drug delivery platform based on liposomes (nano-sized lipid vesicles) for the treatment of experimental RA.
Methods: We employed liposomes as carriers of a near-infra red dye (cyanine 7) or an anti-arthritic drug, dexamethasone, for this proof-of-concept study. These liposomes displayed on their surface polyethylene glycol, to minimize their clearance by the reticuloendothelial system, with or without the peptide. This peptide preferentially targets arthritic joints, while sparing healthy joints, following intravenous or subcutaneous injection. Rats having adjuvant arthritis (AA) or mice having collagen antibody-induced arthritis (CAIA) were injected with Cy7-liposomes and then subjected to live imaging using Xenogen (IVIS). Another set of animals were treated with liposomal dexamethasone or unpackaged (free) dexamethasone, beginning at the onset of arthritis and then continued on alternate days thereafter. The severity of arthritis was graded as “Arthritic Scores”. The sera of these animals were tested for defined markers of systemic toxicity.
Results: Live imaging showed a high fluorescence intensity signal (indicating the accumulation of Cy7-liposomes) emitted from the joints of arthritic animals, but not those of healthy animals, optimally at 4 h after injection. These results are of significance in validating the preferential homing of the liposomes displaying the peptide into the diseased joints of both arthritic rats and arthritic mice. In addition, in both the disease models, liposomal dexamethasone was more effective in suppressing arthritic inflammation in the paws of rats/mice than that delivered as unpackaged dexamethasone. However, unlike efficacy difference, the systemic toxicity profiles of these treatment modalities were comparable.
Conclusion: Taken together, the therapeutic profile of dexamethasone was significantly improved by using peptide-displaying liposomes. Our results offer a proof-of concept for the benefits of targeted drug delivery to the joints for arthritis therapy. We hope that after appropriate modifications, this drug delivery platform might also be suitable for use in RA patients.
To cite this abstract in AMA style:
Nanjaiah H, Meka R, Acharya B, Venkatesha S, Moudgil K. A Joint-targeting Peptide Enhances the Therapeutic Efficacy of Liposomal Drug Delivery in Experimental Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/a-joint-targeting-peptide-enhances-the-therapeutic-efficacy-of-liposomal-drug-delivery-in-experimental-rheumatoid-arthritis/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-joint-targeting-peptide-enhances-the-therapeutic-efficacy-of-liposomal-drug-delivery-in-experimental-rheumatoid-arthritis/