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Molecular targets in arthritis and recent trends in nanotherapy.

Roy K, Kanwar RK, Kanwar JR - Int J Nanomedicine (2015)

Bottom Line: Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities.Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers.The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis.

View Article: PubMed Central - PubMed

Affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), Strategic Research Centre, School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.

ABSTRACT
Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

No MeSH data available.


Related in: MedlinePlus

Targeted nanoparticle (NP) approach in rheumatoid arthritis.Notes: Diagrammatic representation of key targeted NP approaches in treatment of rheumatoid arthritis. The NPs used so far include poly(lactic-co-glycolic acid) (PLGA) NPs targeted with antibody against macrophage-specific receptor-CD64, lipase-labile fumagillin (Fum-PD) was achieved using perfluorocarbon targeted with αvβ3-integrin peptidomimetic antagonists, tocilizumab (TCZ) loaded HA-AuNPs targeted with monoclonal antibody against interleukin-6 (IL-6), Methotrexate (MTX) loaded theranostic gold (Au) half-shell NPs targeted with arginine-glycine-aspartate (RGD) peptides and PLGA NPs targeted with RGD peptides for STAT1 siRNA delivery.
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f3-ijn-10-5407: Targeted nanoparticle (NP) approach in rheumatoid arthritis.Notes: Diagrammatic representation of key targeted NP approaches in treatment of rheumatoid arthritis. The NPs used so far include poly(lactic-co-glycolic acid) (PLGA) NPs targeted with antibody against macrophage-specific receptor-CD64, lipase-labile fumagillin (Fum-PD) was achieved using perfluorocarbon targeted with αvβ3-integrin peptidomimetic antagonists, tocilizumab (TCZ) loaded HA-AuNPs targeted with monoclonal antibody against interleukin-6 (IL-6), Methotrexate (MTX) loaded theranostic gold (Au) half-shell NPs targeted with arginine-glycine-aspartate (RGD) peptides and PLGA NPs targeted with RGD peptides for STAT1 siRNA delivery.

Mentions: There have been very few attempts in the field of targeted delivery of anti-inflammatory agents in RA (Figure 3) and most of the studies have under-achieved in terms of disease-specific targeting. Few considerable efforts include delivery of MTX using poly(lactic-co-glycolic acid) NPs targeted with antibody against macrophage-specific receptor-CD64 in an in vitro model using RAW 264.7 cells.92 It was observed that the MTX-loaded NPs were more effective than the free drug. In another study, delivery of lipase-labile fumagillin prodrug (Fum-PD) was achieved using perfluorocarbon targeted with αvβ3-integrin peptidomimetic antagonists.93,94 Fum-PD nanotherapy induces the production of endothelial nitric oxide by which it indirectly suppresses inflammation in experimental RA. Tocilizumab-loaded hyaluronate-gold nanoparticles targeted with a monoclonal antibody against IL-6 have also been tested in CIA mice.95 In another study, the delivery of MTX was achieved using theranostic gold half-shell NPs targeted with RGD peptides.96 It was revealed that a much smaller dose of these NPs showed greater therapeutic effects than that of a conventional treatment with MTX solution in CIA mice. Poly(lactic-co-glycolic acid) NPs targeted with RGD peptides have also been used for STAT1 siRNA delivery, where the presence of RGD peptide on the NPs increased paw tissue uptake in arthritic mice. Furthermore, RGD functionalization increased lung delivery of NPs in arthritic mice but not in control mice. STAT1 was silenced leading to an increase in expression of Mrc-1 and IL-10 mRNA.97


Molecular targets in arthritis and recent trends in nanotherapy.

Roy K, Kanwar RK, Kanwar JR - Int J Nanomedicine (2015)

Targeted nanoparticle (NP) approach in rheumatoid arthritis.Notes: Diagrammatic representation of key targeted NP approaches in treatment of rheumatoid arthritis. The NPs used so far include poly(lactic-co-glycolic acid) (PLGA) NPs targeted with antibody against macrophage-specific receptor-CD64, lipase-labile fumagillin (Fum-PD) was achieved using perfluorocarbon targeted with αvβ3-integrin peptidomimetic antagonists, tocilizumab (TCZ) loaded HA-AuNPs targeted with monoclonal antibody against interleukin-6 (IL-6), Methotrexate (MTX) loaded theranostic gold (Au) half-shell NPs targeted with arginine-glycine-aspartate (RGD) peptides and PLGA NPs targeted with RGD peptides for STAT1 siRNA delivery.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554438&req=5

f3-ijn-10-5407: Targeted nanoparticle (NP) approach in rheumatoid arthritis.Notes: Diagrammatic representation of key targeted NP approaches in treatment of rheumatoid arthritis. The NPs used so far include poly(lactic-co-glycolic acid) (PLGA) NPs targeted with antibody against macrophage-specific receptor-CD64, lipase-labile fumagillin (Fum-PD) was achieved using perfluorocarbon targeted with αvβ3-integrin peptidomimetic antagonists, tocilizumab (TCZ) loaded HA-AuNPs targeted with monoclonal antibody against interleukin-6 (IL-6), Methotrexate (MTX) loaded theranostic gold (Au) half-shell NPs targeted with arginine-glycine-aspartate (RGD) peptides and PLGA NPs targeted with RGD peptides for STAT1 siRNA delivery.
Mentions: There have been very few attempts in the field of targeted delivery of anti-inflammatory agents in RA (Figure 3) and most of the studies have under-achieved in terms of disease-specific targeting. Few considerable efforts include delivery of MTX using poly(lactic-co-glycolic acid) NPs targeted with antibody against macrophage-specific receptor-CD64 in an in vitro model using RAW 264.7 cells.92 It was observed that the MTX-loaded NPs were more effective than the free drug. In another study, delivery of lipase-labile fumagillin prodrug (Fum-PD) was achieved using perfluorocarbon targeted with αvβ3-integrin peptidomimetic antagonists.93,94 Fum-PD nanotherapy induces the production of endothelial nitric oxide by which it indirectly suppresses inflammation in experimental RA. Tocilizumab-loaded hyaluronate-gold nanoparticles targeted with a monoclonal antibody against IL-6 have also been tested in CIA mice.95 In another study, the delivery of MTX was achieved using theranostic gold half-shell NPs targeted with RGD peptides.96 It was revealed that a much smaller dose of these NPs showed greater therapeutic effects than that of a conventional treatment with MTX solution in CIA mice. Poly(lactic-co-glycolic acid) NPs targeted with RGD peptides have also been used for STAT1 siRNA delivery, where the presence of RGD peptide on the NPs increased paw tissue uptake in arthritic mice. Furthermore, RGD functionalization increased lung delivery of NPs in arthritic mice but not in control mice. STAT1 was silenced leading to an increase in expression of Mrc-1 and IL-10 mRNA.97

Bottom Line: Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities.Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers.The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis.

View Article: PubMed Central - PubMed

Affiliation: Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), Centre for Molecular and Medical Research (C-MMR), Strategic Research Centre, School of Medicine (SoM), Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia.

ABSTRACT
Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

No MeSH data available.


Related in: MedlinePlus