title: Targeting fibroblast-like synovial cells at sites of inflammation with peptide targeted liposomes results in inhibition of experimental arthritis.
abstract: In this study we examined a synovium-specific targeted liposomal drug delivery system for its ability to localize and release its drug cargo to inflamed joints. Targeted liposomes were tested in vitro for binding to synovial fibroblast like (FLS) and endothelial cells using flow cytometry and in vivo for localization to joints using a rat model of adjuvant induced arthritis (AIA). Targeted liposomes were then loaded with anti-arthritic medications and examined for clinical efficacy in AIA. Targeted liposomes specifically bound to rabbit FLS and human FLS and showed a 7-10 fold increase in vivo localization in affected joints compared to unaffected joints. Histological sections from rats treated with prednisone and a new immunosuppressive peptide CP showed minimal inflammation. This report substantiates the ability of the novel FLS sequence to target liposomal drug delivery and offers an alternative therapeutic approach for the treatment of arthritis.
authors: Department of Rheumatology, Westmead Hospital, Sydney, Australia. Electronic address: Nicholas.manolios@sydney.edu.au.
authors: A S
authors: AS
authors: Vanniasinghe
authors: Department of Rheumatology, Westmead Hospital, Sydney, Australia.
authors: N
authors: N
authors: Manolios
authors: Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.
authors: S
authors: S
authors: Schibeci
authors: Department of Rheumatology, Westmead Hospital, Sydney, Australia.
authors: C
authors: C
authors: Lakhiani
authors: Department of Rheumatology, Westmead Hospital, Sydney, Australia.
authors: E
authors: E
authors: Kamali-Sarvestani
authors: Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.
authors: R
authors: R
authors: Sharma
authors: Department of Nuclear Medicine & PET Westmead Hospital, Sydney, Australia.
authors: V
authors: V
authors: Kumar
authors: CSIRO Molecular & Health Technologies, Sydney, Australia.
authors: M
authors: M
authors: Moghaddam
authors: Department of Rheumatology, Westmead Hospital, Sydney, Australia.
authors: M
authors: M
authors: Ali
authors: Department of Rheumatology, Westmead Hospital, Sydney, Australia.
authors: V
authors: V
authors: Bender
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006614:Hindlimb; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008081:Liposomes / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011725:Pyridines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D008081:Liposomes; D009842:Oligopeptides; D010455:Peptides; D011725:Pyridines; D011743:Pyrimidines; C502271:methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate; C047981:arginyl-glycyl-aspartic acid; D011241:Prednisone
keywords: Adjuvant-induced arthritis; Arthritis; Drug delivery; Fibroblast-like synovial cells; Liposomes; Peptides