The authors reported that this liposomal formulation exhibited high encapsulation efficacy (94%) and a high drug-lipid mole ration (0.41). of liposomes leading to increased uptake of drugs by the target synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging styles of this encouraging technology. 1. Introduction Rheumatoid arthritis (RA) is usually a systemic autoimmune inflammatory disease that affects the multiple joints of the body in a symmetric pattern [1, 2]. It is characterised by chronic inflammation of synovial membrane which often prospects to destruction of articular cartilage, periarticular bone erosion, and permanent deformities. Classically, it causes synovitis in the metacarpophalangeal and proximal interphalangeal joints in a symmetrical manner. Clinically, it is manifested as warmness, swelling, tenderness with loss of motion, and grip strength in hands. RA generally affects the feet, wrists, and knees, as well as cervical spine, shoulders, and hips [3]. At least 50% of patients with RA experience work disability within 10 years of onset of disease [4]. RA can also have systemic effects such as subcutaneous nodule development, pleural effusion, and pericarditis [5]. The prevalence of RA in general population has been estimated to be 0.8% and the incidence of RA in women is 3C5 times higher than in men [6, 7]. In India and China alone, about 19 million people are affected by RA [8]. Although it affects persons of all age groups, it is particularly prevalent in middle age populace of 30C50 years. The mean life expectancy of patients suffering from RA has been reported to be reduced by 5C10 years; however, this also depends on severity of the disease [9]. The precise etiology of RA is not known, but it is usually obvious that proinflammatory cytokines such as tumor necrosis factor-(TNF-(TGF-(TNF-antagonists (golimumab and certolizumab pegol), and monoclonal antibodies against numerous cytokines or targeting antagonist is usually bacterial and fungal contamination, for example, tuberculosis is usually common in patients receiving infliximab. Malignancy may also be associated with use of anti-TNF-therapy, especially non-Hodgkin’s lymphoma is usually reported [2]. 7. Natural Agents Natural brokers including flavonoids, terpenes, quinones, catechins, alkaloids, anthocyanins, and anthoxanthins are known to exhibit anti-inflammatory activity. Curcumin, resveratrol, guggulsterone, withanolide, boswellic acid, and 6-shogaol are some of the polyphenols that have been tested for the treatment of arthritis [27]. All these herbal drugs suppress the activation of nuclear factor-kB and thus lead to downregulation of the expression of TNF-[28], adhesion molecules [29], metalloproteinase [30], cyclooxygenase-2 [30], 5-lipoxygenase [31], and other inflammatory intermediates [32], all of which are associated with arthritis. Curcumin has also been shown to suppress the expression of TNF-and studies [34, 35]. Withanolides, found in from macrophages, potent anti-inflammatory activity[108]22MethotrexatePEG-liposomesRatCollagen induces arthritisIntravenousInhibitors release of TRAIL-R2 both IL-1and PGE2 form macrophages[109]23MethotrexateLarge multilamellar vesiclesRatAntigen-induced arthritisIntra-articularInhibition of both IL-1and IL-6 mRNA expression in synovial tissue, reduce knee swelling, Inhibit progression of antigen-induced arthritis[110]24MethotrexatePEGylted liposomesWistar-Lewis ratAdjuvant arthritisIntravenousIncreased physical stability and entrapment efficacy, significant anti-inflammatory activity[61]25MethotrexateNot definedWistar RatAdjuvant arthritisIntravenousReduced toxicity[111] 26ClodronateNot definedMiceCollagen induces arthritisIntra-articularReduced joint swelling, significantly decreased chondrocyte death, Reduced cartilage destruction[112, 113] 27ClodronateMultilamellar vesiclesRatAdjuant arthritis, antigen-induced arthritisIntravenousReduction of macrophages in synovial membrane, liver, and spleen, reduced inflammation and joint destruction[114C116]28ClodronateUnilamellar liposomesHuman RA patientsIntra-articularDecreased synovial lining macrophages and expression of adhesion molecules, reduced cartilage destruction[117] 29ClodronateNot definedRabbitAntigen-induced arthritisIntra-articularLow level of macrophages in synovium, reduction in joint swelling, sustained action of drug[118]30ClodronateSmall unilamellar vesiclesLewis ratStreptococcal cell wallinduced arthritisIntravenousDepletion of macrophages, inhibited the production of proinflammatory cytokines, decreased progression of disease[119]31ClodronateMultilamellar vesiclesSheepAntigen-induced arthritisIntravenousNo significant anti-inflammatory effect[120] 32Superoxide dismutaseStearylamine and PEG liposomesWistar ratAntigen-induced arthritisIntravenousPotent anti-inflammatory activity[121, 122]33Superoxide dismutaseLiposomes and transfersomesWistar ratAdjuvant arthritisEpicutaneousSignificant reduction in inflammation[123]34Superoxide dismutaseNot definedRatAdjuvant arthritisSubcutaneousSignificant anti-inflammatory activity[124]35Superoxide dismutaseMultilamellar and PEGylated liposomesWistar ratAdjuvant arthritisIntravenousFaster anti-inflammatory activity[125]36Superoxide dismutaseNot definedHumanHuman RAIntramuscularSignificant improvement in clinical signs of inflammation[126]37LactoferrinNot definedMiceCollagen-induced arthritisIntra-articularIncreased retention of drug in joints, reduced proinflammatory (TNF) and increased anti-inflammatory (IL-10) cytokine production[127, 128]38Boron neutron capture therapyNot definedLouvain ratCollagen-induced arthritisIntravenousHigh concentration.Moreover, both groups showed joint swelling which persisted until the end of the study [120]. A comparative study of small unilamellar and large multilamellar vesicles of clodronate was conducted in rats with antigen-induced arthritis. sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging trends of this promising technology. 1. Introduction Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease that affects the multiple joints of the body in a symmetric pattern [1, 2]. It is characterised by chronic inflammation of synovial membrane which often leads to destruction of articular cartilage, periarticular bone erosion, and permanent deformities. Classically, it causes synovitis in the metacarpophalangeal and proximal interphalangeal joints in a symmetrical manner. Clinically, it is manifested as warmth, swelling, tenderness with loss of motion, and grip strength in hands. RA commonly affects the feet, wrists, and knees, as well as cervical spine, shoulders, and hips [3]. At least 50% of patients with RA experience work disability within 10 years of onset of disease [4]. RA can also have systemic effects such as subcutaneous nodule development, pleural effusion, and pericarditis [5]. The prevalence of RA in general population has been estimated to be 0.8% and the incidence of RA in women is 3C5 times higher than in men [6, 7]. In India and China alone, about 19 million people are affected by RA [8]. Although it affects persons of all age groups, it is particularly prevalent in middle age population of 30C50 years. The mean life expectancy of patients suffering from RA has been reported to be reduced by 5C10 years; however, this also depends on severity of the disease [9]. The precise etiology of RA is not known, but it is evident that proinflammatory cytokines such as tumor necrosis factor-(TNF-(TGF-(TNF-antagonists (golimumab and certolizumab pegol), and monoclonal antibodies against various cytokines or targeting antagonist is bacterial and fungal infection, for example, tuberculosis is common in patients receiving infliximab. Malignancy may also be associated with use of anti-TNF-therapy, especially non-Hodgkin’s lymphoma is reported [2]. 7. Natural Agents Natural agents including flavonoids, terpenes, quinones, catechins, alkaloids, anthocyanins, and anthoxanthins are known to exhibit Icotinib Hydrochloride anti-inflammatory activity. Curcumin, resveratrol, guggulsterone, withanolide, boswellic acid, and 6-shogaol are some of the polyphenols that have been tested for the treatment of arthritis [27]. All these herbal drugs suppress the activation of nuclear factor-kB and thus lead to downregulation of the expression of TNF-[28], adhesion molecules [29], metalloproteinase [30], cyclooxygenase-2 [30], 5-lipoxygenase [31], and other inflammatory intermediates [32], all of which are associated with arthritis. Curcumin has also been shown to suppress the expression of TNF-and studies [34, 35]. Withanolides, found in from macrophages, potent anti-inflammatory activity[108]22MethotrexatePEG-liposomesRatCollagen induces arthritisIntravenousInhibitors release of both IL-1and PGE2 form macrophages[109]23MethotrexateLarge multilamellar vesiclesRatAntigen-induced arthritisIntra-articularInhibition of both IL-1and IL-6 mRNA expression in synovial tissue, reduce knee swelling, Inhibit progression of antigen-induced arthritis[110]24MethotrexatePEGylted liposomesWistar-Lewis ratAdjuvant arthritisIntravenousIncreased physical stability and entrapment efficacy, significant anti-inflammatory activity[61]25MethotrexateNot definedWistar RatAdjuvant arthritisIntravenousReduced toxicity[111] 26ClodronateNot definedMiceCollagen induces arthritisIntra-articularReduced joint swelling, significantly decreased chondrocyte death, Reduced cartilage destruction[112, 113] 27ClodronateMultilamellar vesiclesRatAdjuant arthritis, antigen-induced arthritisIntravenousReduction of macrophages in synovial membrane, liver, and spleen, reduced inflammation and joint damage[114C116]28ClodronateUnilamellar liposomesHuman RA Icotinib Hydrochloride patientsIntra-articularDecreased synovial lining macrophages and manifestation of adhesion molecules, reduced cartilage damage[117] 29ClodronateNot definedRabbitAntigen-induced arthritisIntra-articularLow level of macrophages in synovium, reduction in joint swelling, sustained action of drug[118]30ClodronateSmall unilamellar vesiclesLewis ratStreptococcal cell wallinduced arthritisIntravenousDepletion of macrophages, inhibited the production of proinflammatory cytokines, decreased progression of disease[119]31ClodronateMultilamellar vesiclesSheepAntigen-induced arthritisIntravenousNo significant anti-inflammatory effect[120] 32Superoxide dismutaseStearylamine and PEG liposomesWistar ratAntigen-induced arthritisIntravenousPotent anti-inflammatory activity[121, 122]33Superoxide dismutaseLiposomes and transfersomesWistar ratAdjuvant arthritisEpicutaneousSignificant reduction in swelling[123]34Superoxide dismutaseNot.In short-term treatment, standard liposomes showed higher anti-inflammatory activity than long-circulation liposomes. intra-synovially given drugs can be conquer by use of liposomes leading to improved uptake of medicines by the prospective synovial cells, which in turn reduces the exposure of nontarget sites and eliminates most of the undesirable effects associated with therapy. This review focuses on the use of liposomes in treatment of rheumatoid arthritis and summarizes data relating to the liposome formulations of various drugs. It also discusses emerging styles of this encouraging technology. 1. Intro Rheumatoid arthritis (RA) is definitely a systemic autoimmune inflammatory disease that affects the multiple bones of the body inside a symmetric pattern [1, 2]. It is characterised by chronic swelling of synovial membrane which often leads to damage of articular cartilage, periarticular bone erosion, and long term deformities. Classically, it causes synovitis in the metacarpophalangeal and proximal interphalangeal bones inside a symmetrical manner. Clinically, it is manifested as heat, swelling, tenderness with loss of motion, and grip strength in hands. RA generally affects your toes, wrists, and knees, as well as cervical spine, shoulders, and hips [3]. At least 50% of individuals with RA encounter work disability within 10 years of onset of disease [4]. RA can also have systemic effects such Icotinib Hydrochloride as subcutaneous nodule development, pleural effusion, and pericarditis [5]. The prevalence of RA in general population has been estimated to be 0.8% and the incidence of RA in ladies is 3C5 times higher than in men [6, 7]. In India and China only, about 19 million people are affected by RA [8]. Although it affects persons of all age groups, it is particularly common in middle age human population of 30C50 years. The mean life expectancy of patients suffering from RA has been reported to be reduced by 5C10 years; however, this also depends on severity of the disease [9]. The precise etiology of RA is not known, but it is definitely obvious that proinflammatory cytokines such as tumor necrosis element-(TNF-(TGF-(TNF-antagonists (golimumab and certolizumab pegol), and monoclonal antibodies against numerous cytokines or focusing on antagonist is definitely bacterial and fungal illness, for example, tuberculosis is definitely common in individuals receiving infliximab. Malignancy may also be associated with use of anti-TNF-therapy, especially non-Hodgkin’s lymphoma is definitely reported [2]. 7. Organic Agents Natural providers including flavonoids, terpenes, quinones, catechins, alkaloids, anthocyanins, and anthoxanthins are known to show anti-inflammatory activity. Curcumin, resveratrol, guggulsterone, withanolide, boswellic acid, and 6-shogaol are some of the polyphenols that have been tested for the treatment of arthritis [27]. All these natural medicines suppress the activation of nuclear factor-kB and thus lead to downregulation of the manifestation of TNF-[28], adhesion molecules [29], metalloproteinase [30], cyclooxygenase-2 [30], 5-lipoxygenase [31], and additional inflammatory intermediates [32], all of which are associated with arthritis. Curcumin has also been shown to suppress the manifestation of TNF-and studies [34, 35]. Withanolides, found in from macrophages, potent anti-inflammatory activity[108]22MethotrexatePEG-liposomesRatCollagen induces arthritisIntravenousInhibitors launch of both IL-1and PGE2 form macrophages[109]23MethotrexateLarge multilamellar vesiclesRatAntigen-induced arthritisIntra-articularInhibition of both IL-1and IL-6 mRNA manifestation in synovial cells, reduce knee swelling, Inhibit progression of antigen-induced arthritis[110]24MethotrexatePEGylted liposomesWistar-Lewis ratAdjuvant arthritisIntravenousIncreased physical stability and entrapment effectiveness, significant anti-inflammatory activity[61]25MethotrexateNot definedWistar RatAdjuvant arthritisIntravenousReduced toxicity[111] 26ClodronateNot definedMiceCollagen induces arthritisIntra-articularReduced joint swelling, significantly decreased chondrocyte death, Reduced cartilage damage[112, 113] 27ClodronateMultilamellar vesiclesRatAdjuant arthritis, antigen-induced arthritisIntravenousReduction of macrophages in synovial membrane, liver, and spleen, reduced swelling and joint Icotinib Hydrochloride damage[114C116]28ClodronateUnilamellar liposomesHuman RA patientsIntra-articularDecreased synovial lining macrophages and manifestation of adhesion molecules, reduced cartilage damage[117] 29ClodronateNot definedRabbitAntigen-induced arthritisIntra-articularLow level of macrophages in synovium, reduction in joint swelling, sustained action of drug[118]30ClodronateSmall unilamellar vesiclesLewis ratStreptococcal cell wallinduced arthritisIntravenousDepletion of macrophages, inhibited the production of proinflammatory cytokines, decreased progression of disease[119]31ClodronateMultilamellar vesiclesSheepAntigen-induced arthritisIntravenousNo significant anti-inflammatory effect[120] 32Superoxide dismutaseStearylamine and PEG liposomesWistar ratAntigen-induced arthritisIntravenousPotent anti-inflammatory activity[121, 122]33Superoxide dismutaseLiposomes and transfersomesWistar ratAdjuvant arthritisEpicutaneousSignificant reduction in swelling[123]34Superoxide dismutaseNot definedRatAdjuvant arthritisSubcutaneousSignificant anti-inflammatory activity[124]35Superoxide dismutaseMultilamellar and PEGylated liposomesWistar ratAdjuvant arthritisIntravenousFaster anti-inflammatory activity[125]36Superoxide dismutaseNot definedHumanHuman RAIntramuscularSignificant improvement in medical signs of swelling[126]37LactoferrinNot definedMiceCollagen-induced arthritisIntra-articularIncreased retention of drug in joints, reduced proinflammatory (TNF) and improved.