S. No Drug Liposomal type Animal used Animal model Route of administration Observed effect Reference 1 Indomethacin Large unilamellar vesicles Rat Carrageenan induced paw edema and Adjuvant arthritis Intra-peritoneal Increase anti-inflammatory activity, less ulcer index [79 ] 2 Diclofenac sodium Lipogelosome Rabbit Antigen-induced arthritis Intra-articular Reduce side effects, increase retention of drug at inflammatory site
[6 , 66 ] 3 Cortisol palmitate Not defined Rabbit Poly-D-lysine and hyaluronic acid complex injection Intra-articular Reduce temperature and diameter in arthritic joints [89 ] 4 Hydrocortisone Multilamellar liposomes Rabbit Antigen-induced arthritis Intra-articular Prolong anti-inflammatory effect [90 ] 5 Prednisolone phosphate PEG-liposomes Mice Collagen type-II and adjuvant-induced arthritis Intravenous Reduce cartilage damage [91 ] 6 Methyl prednisolone hemisuccinate Nanoliposomes Lewis rat, Beagle dog Adjuvant arthritis Intravenous High encapsulation efficacy, [92 ] 7 Prednisolone phosphate Not defined Mice Antigen-induced arthritis Intravenous Suppression of bone erosion, less synovial immune cell infiltration, Suppress metalloproteases and aggrecanases in synovium [93 , 94 ] 8 Methyl prednisolone hemisuccinate Nanoliposomes Lewis rat Adjuvant arthritis Intravenous or subcutaneous Reduce arthritis, suppression of secretion of proinflammatory cytokines [95 ] 9 Betamethasone hemisuccinate Nanoliposomes Lewis rat Adjuvant arthritis Intravenous or subcutaneous Reduce arthritis, suppression of secretion of proinflammatory cytokines [95 ] 10 Dexamethasone phosphate Oligolamellar and multilamellar vesicles Rabbit Antigen-induced arthritis Intra-articular Increase retention of drug in synovium and synovial fluid [96 , 97 ] 11 Dexamethasone phosphate RGD-PEG-Liposomes Lewis rat Antigen-induced arthritis Intravenous Strong and long-lasting antiarthritic effect, specifically target vesicular endothelial sites at site of inflammation [98 ] 12 Dexamethasone phosphate Non-PEGlyated liposomes Rat Antigen-induced arthritis Intravenous Suppress joint swelling [99 ] 13 Dexamethasone phosphate Non-PEGlyated liposomes Mouse Collagen induces arthritis Intravenous Persistent anti-inflammatory effect, [100 ] 14 Dexamethasone phosphate Not defined Lewis rat Adjuvant arthritis Intravenous Suppression of histological signs of arthritis, increased residence time of drug in synovial membrane [101 ] 15 Dexamethasone, budesonide, prednisolone Long circulating liposomes Rat Adjuvant arthritis, collagen-induced arthritis Intravenous Increase therapeutic efficacy, [98 , 102 ] 16 Triamcinolone Not defined Rabbit Carrageenan-induced paw edema Intra-articular Effectively suppress arthritis, longer retention of drug in articular cavity [103 ] 17 Sodium aurothiomalate Small unilamellar vesicles Mice Collagen induces arthritis Intra-muscular Inhibit cellular infiltration of lymphocytes into the synovium, [11 ] 18 Methotrexate Not defined Rabbit Antigen-induced arthritis Intra-articular Long retention of drug in joints, suppressed joint swelling and rise in temperature, Decrease in synovial hyperplasia, cellular infiltration and cartilage erosion [104 , 105 ] 19 Methotrexate Small unilamellar vesicles Rat Adjuvant-induced arthritis Intravenous Significant anti-inflammatory effect [106 ] 20 Methotrexate Multilamellar vesicles Rat Antigen-induced arthritis Intra-articular Significant anti-inflammatory effect, Inhibit cellular infiltration [107 ] 21 Methotrexate Small unilamellar vesicles Rat Collagen induces arthritis Intravenous Inhibit the release of IL-1
from macrophages, potent anti-inflammatory activity [108 ] 22 Methotrexate PEG-liposomes Rat Collagen induces arthritis Intravenous Inhibitors release of both IL-1
and PGE2 form macrophages [109 ] 23 Methotrexate Large multilamellar vesicles Rat Antigen-induced arthritis Intra-articular Inhibition of both IL-1
and IL-6 mRNA expression in synovial tissue, reduce knee swelling, Inhibit progression of antigen-induced arthritis [110 ] 24 Methotrexate PEGylted liposomes Wistar-Lewis rat Adjuvant arthritis Intravenous Increased physical stability and entrapment efficacy, significant anti-inflammatory activity [61 ] 25 Methotrexate Not defined Wistar Rat Adjuvant arthritis Intravenous Reduced toxicity [111 ] 26 Clodronate Not defined Mice Collagen induces arthritis Intra-articular Reduced joint swelling, significantly decreased chondrocyte death, Reduced cartilage destruction [112 , 113 ] 27 Clodronate Multilamellar vesicles Rat Adjuant arthritis, antigen-induced arthritis Intravenous Reduction of macrophages in synovial membrane, liver, and spleen, reduced inflammation and joint destruction [114 –116 ] 28 Clodronate Unilamellar liposomes Human RA patients Intra-articular Decreased synovial lining macrophages and expression of adhesion molecules, reduced cartilage destruction [117 ] 29 Clodronate Not defined Rabbit Antigen-induced arthritis Intra-articular Low level of macrophages in synovium, reduction in joint swelling, sustained action of drug [118 ] 30 Clodronate Small unilamellar vesicles Lewis rat Streptococcal cell wall—induced arthritis Intravenous Depletion of macrophages, inhibited the production of proinflammatory cytokines, decreased progression of disease [119 ] 31 Clodronate Multilamellar vesicles Sheep Antigen-induced arthritis Intravenous No significant anti-inflammatory effect [120 ] 32 Superoxide dismutase Stearylamine and PEG liposomes Wistar rat Antigen-induced arthritis Intravenous Potent anti-inflammatory activity [121 , 122 ] 33 Superoxide dismutase Liposomes and transfersomes Wistar rat Adjuvant arthritis Epicutaneous Significant reduction in inflammation [123 ] 34 Superoxide dismutase Not defined Rat Adjuvant arthritis Subcutaneous Significant anti-inflammatory activity [124 ] 35 Superoxide dismutase Multilamellar and PEGylated liposomes Wistar rat Adjuvant arthritis Intravenous Faster anti-inflammatory activity [125 ] 36 Superoxide dismutase Not defined Human Human RA Intramuscular Significant improvement in clinical signs of inflammation [126 ] 37 Lactoferrin Not defined Mice Collagen-induced arthritis Intra-articular Increased retention of drug in joints, reduced proinflammatory (TNF) and increased anti-inflammatory (IL-10) cytokine production [127 , 128 ] 38 Boron neutron capture therapy Not defined Louvain rat Collagen-induced arthritis Intravenous High concentration of boron in synovium [129 ]
