Recent approaches for targeted drug delivery in rheumatoid arthritis diagnosis and treatment

Figures & data

Table 1. Summary of targeted delivery systems for RA to increase targeting effect.

Targeting agent	Receptor	Delivery systems	Drug	References
Folic acid	Folate receptors	PLGA nanoparticles	Dexamethasone phosphate	[10]
		Liposome	Methotrexate	[11]
		Poly(amidoamide) dendrimers	Methotrexate	[12]
		Poly(amidoamide) dendrimers	Indomethacin	[13]
		Albumin	Etoricoxib	[14]
		Dextran	Methotrexate	[15]
		Chitosan	IL-1Ra DNA	[53]
Hyaluronic acid	CD44 receptor	Hyaluronic acid – 5β-Cholanic acid	γ-Secretase inhibitors	[16]
		Biomineral-installed hyaluronan nanoparticles	Methotrexate	[17]
		Ionic complex systems based on hyaluronic acid and PEGylated TRAIL	TRAIL	[18]
		HA- 1,2-distearoylphosphatidylethanolamine	Triamcinolone	[34]
Dextran sulfate	Macrophage scavenger receptor class A	Dextran sulphate –polycaprolactone	Cy5.5	[19]
		Dextran sulphate -5β-cholanic acid	Methotrexate	[20]
RGD	Integrin receptor	Albumin	SB202190	[23]
		PEG-Liposomes	Dexamethasone phosphate	[24]
		Liposomes	CP or prednisolone	[25]
		Gold half shell PLGA NPs	Methotrexate	[41]
		PLGA gold/iron/gold half-shell NPs	Methotrexate	[48]
HAP 1		PTD-(KLAK)2 conjugate	(KLAK)2	[27]
		Liposomes	CP or prednisolone	[28]
Vasoactive intestinal peptide	VIP receptors	DSPE-PEG3400	Camptothecin	[29]
CD 163 monoclonal antibody	Haemoglobin scavenger receptor CD163	Liposome	Doxorubicin Murine interleukin-10	[30]
Tuftsin	Fc and neuropilin-1(NP-1) receptors	Alginate NPs	Plasmid DNA	[58]

Figure 1. Fluorescence images of inflamed joints (a) and fluorescence intensity detected from affected joints of CIA mice treated with administration of Dex-MTX, FA/Dex-MTX, free MTX and normal saline intravenously (Reproduced with permission from Journal of Materials Chemistry (b) [15]).

Figure 2. Schematic illustration of targeting mechanism of DS-b-PCL nanoparticles as the constituents of diagnostic and therapeutic formulations for RA (Reproduced with permission from Royal Society of Chemistry [19]).

Figure 3. Mean clinical scores for arthritis paws treated with (a) PBS, (b) HA-AuNPs, (c) TCZ and (d) HA-AuNPs/TCZ complex (Reproduced with permission from American Chemical Society [39]).

Figure 4. (a) Schematic depicting preparation of RGD-MTX-PLGA-AuNPs. (b) Application of RGD-MTX-PLGA-AuNPs for in vivo RA treatment (Reproduced with permission from American Chemical Society [41]).

Figure 5. In vitro release of MTX from RGD-MTX-PLGA-AuNPs with or without NIR exposure (Reproduced with permission from American Chemical Society [41]).

Cao J, Naeem M, Noh JK, et al. Dexamethasone phosphate-loaded folate-conjugated polymeric nanoparticles for selective delivery to activated macrophages and suppression of inflammatory responses. Macromol Res. 2015;23:485–492.

 Web of Science ®Google Scholar

Nogueira E, Lager F, Le Roux D, et al. Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice. J Biomed Nanotechnol. 2015;11:2243–2252.

 PubMed Web of Science ®Google Scholar

Qi R, Majoros I, Misra AC, et al. Folate receptor-targeted dendrimer-methotrexate conjugate for inflammatory arthritis. J Biomed Nanotechnol. 2015;11:1431–1441.

 PubMed Web of Science ®Google Scholar

Chandrasekar D, Sistla R, Ahmad FJ, et al. Folate coupled poly(ethyleneglycol) conjugates of anionic poly(amidoamine) dendrimer for inflammatory tissue specific drug delivery. J Biomed Mater Res. 2007;82:92–103.

 Web of Science ®Google Scholar

Bilthariya U, Jain N, Rajoriya V, et al. Folate-conjugated albumin nanoparticles for rheumatoid arthritis-targeted delivery of etoricoxib. Drug Dev Ind Pharm. 2015;41:95–104.

 PubMed Web of Science ®Google Scholar

Yang M, Ding J, Zhang Y, et al. Activated macrophage-targeted dextran–methotrexate/folate conjugate prevents deterioration of collagen-induced arthritis in mice. J Mater Chem B. 2016;4:2102–2113.

 PubMed Web of Science ®Google Scholar

Fernandes JC, Wang H, Jreyssaty C. Bone-protective effects of nonviral gene therapy with folate–chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis. Mol Ther. 2008;16:1243–1251.

 PubMed Web of Science ®Google Scholar

Heo R, Park JS, Jang HJ, et al. Hyaluronan nanoparticles bearing γ-secretase inhibitor: in vivo therapeutic effects on rheumatoid arthritis. J Control Release. 2014;192:295–300.

 PubMed Web of Science ®Google Scholar

Alam MM, Han HS, Sung S, et al. Endogenous inspired biomineral-installed hyaluronan nanoparticles as pH-responsive carrier of methotrexate for rheumatoid arthritis. J Control Release. 2017;252:62–72.

 PubMed Web of Science ®Google Scholar

Kim YJ, Chae SY, Jin CH, et al. Ionic complex systems based on hyaluronic acid and PEGylatedTNF-related apoptosis-inducing ligand for treatment of rheumatoid arthritis. Biomaterials. 2010;31:9057–9064.

 PubMed Web of Science ®Google Scholar

Saadat E, Shakor N, Gholami M, et al. Hyaluronic acid based micelle for articular delivery of triamcinolone, preparation, in vitro and in vivo evaluation. Int J Pharm. 2015;489:218–225.

 PubMed Web of Science ®Google Scholar

Kim SH, Kim JH, You DG, et al. Self-assembled dextran sulphate nanoparticles for targeting rheumatoid arthritis. Chem Commun. 2013;49:10349–10351.

 PubMed Web of Science ®Google Scholar

Heo R, You DG, Um W, et al. Dextran sulfate nanoparticles as a theranostic nanomedicine for rheumatoid arthritis. Biomaterials. 2017;131:15–26.

 PubMed Web of Science ®Google Scholar

Temming K, Lacombe M, van der Hoeven P, et al. Delivery of the p38 MAP kinase inhibitor SB202190 to angiogenic endothelial cells: development of novel RGD-equipped and PEGylated drug-albumin conjugates using platinum(II)-based drug linker technology. Bioconjug Chem. 2006;17:1246–1255.

 PubMed Web of Science ®Google Scholar

Koning GA, Schiffelers RM, Wauben MH, et al. Targeting of angiogenic endothelial cells at sites of inflammation by dexamethasone phosphate-containing RGD peptide liposomes inhibits experimental arthritis. Arthritis Rheum. 2006;54:1198–1208.

 PubMed Web of Science ®Google Scholar

Gerlag DM, Borges E, Tak PP, et al. Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature. Arthritis Res. 2001;3:357–361.

 PubMedGoogle Scholar

Lee SM, Kim HJ, Ha YJ, et al. Targeted chemo-photothermal treatments of rheumatoid arthritis using gold half-shell multifunctional nanoparticles. ACS Nano. 2013;7:50–57.

 PubMed Web of Science ®Google Scholar

Kim HJ, Lee SM, Park KH, et al. Drug-loaded gold/iron/gold plasmonic nanoparticles for magnetic targeted chemo-photothermal treatment of rheumatoid arthritis. Biomaterials. 2015;61:95–102.

 PubMed Web of Science ®Google Scholar

Mi Z, Lu X, Mai JC, et al. Identification of a synovial fibroblast-specific protein transduction domain for delivery of apoptotic agents to hyperplastic synovium. Mol Ther. 2003;8:295–305.

 PubMed Web of Science ®Google Scholar

Vanniasinghe AS, Manolios N, Schibeci S, et al. Targeting fibroblast-like synovial cells at sites of inflammation with peptide targeted liposomes results in inhibition of experimental arthritis. Clin Immunol. 2014;151:43–54.

 PubMed Web of Science ®Google Scholar

Koo OM, Rubinstein I, Onyüksel H. Actively targeted low-dose camptothecin as a safe, long-acting, disease-modifying nanomedicine for rheumatoid arthritis. Pharm Res. 2011;28:776–787.

 PubMed Web of Science ®Google Scholar

Etzerodt A, Maniecki MB, Graversen JH, et al. Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163. J Control Release. 2012;160:72–80.

 PubMed Web of Science ®Google Scholar

Jain S, Amiji M. Tuftsin-modified alginate nanoparticles as a noncondensing macrophage-targeted DNA delivery system. Biomacromolecules. 2012;13:1074–1085.

 PubMed Web of Science ®Google Scholar

Lee H, Lee MY, Bhang SH, et al. Hyaluronate-gold nanoparticle/tocilizumab complex for the treatment of rheumatoid arthritis. ACS Nano. 2014;8:4790–4798.

 PubMed Web of Science ®Google Scholar