Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease characterized by inflammation of the synovial tissue of the joints, which if not controlled early and adequately, may cause severe joint damage and deformity. There are many potent anti-arthritic drugs, which are given orally or by injection, and their prolonged use is associated with many adverse reactions. This is attributable in part to the widespread distribution of the drugs, exposing healthy organs to those drugs. Thus, there is a need for targeted drug delivery methods to direct the drugs primarily to the inflamed joints.
Methods: We developed a peptide-directed liposomal drug delivery system to deliver dexamethasone (DEX) to arthritic joints of rats with adjuvant-induced (AA) arthritis. The peptide ART-2 shows preferential homing to inflamed joints when injected intravenously. Therefore, we exploited this attribute of peptide ART-2 to guide the DEX-entrapping liposomes to arthritic joints. Arthritic rats were treated with test or control liposomes, or free drug after the onset of disease and the severity of arthritis was monitored regularly thereafter. Sera of these rats were tested for assessment of toxicity to liver, kidney, and pancreas.
Results: ART-2-DEX liposomes, when injected intravenously into arthritic rats after the onset of arthritis, were more effective in suppressing disease progression than control-DEX liposomes lacking ART-2 or free DEX at an equivalent dose of this drug. Furthermore, despite increased efficacy, the toxicity profile of ART-2-DEX liposomes was comparable to that of control liposomes or free DEX, thereby resulting in enhanced therapeutic index of DEX therapy.
Conclusion: Our results furnish a proof-of concept for the use of a novel joint-homing peptide for targeted delivery of drugs including biologics or small molecule compounds to arthritic joints with enhanced efficacy and reduced systemic exposure. This targeted therapy platform may be suitable for use in RA patients. (Supported by VA Merit Review I01 BX002424, NIH R01AT004321, and RRF.)
To cite this abstract in AMA style:Meka R, Venkatesha S, Acharya B, Moudgil K. Targeted Drug Delivery Using a Novel Joint-homing Peptide for Arthritis Therapy [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/targeted-drug-delivery-using-a-novel-joint-homing-peptide-for-arthritis-therapy/. Accessed November 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/targeted-drug-delivery-using-a-novel-joint-homing-peptide-for-arthritis-therapy/