Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment

Abstract

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.

Keywords: ACLT, anterior cruciate ligament transection; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; AIA, adjuvant-induced arthritis; AMF, alternating magnetic field; APCs, antigen-presenting cells; BBR, berberine; CAT, catalase; CD44, cluster of differentiation 44; CEL, tripterine; CEL-PRNPs, RGD-modified PLGA enzyme-responsive nanoparticles loaded with tripterine; CIA, collagen-induced arthritis; CTSK, cathepsin K; CaP, calcium phosphate; Cartilage degeneration; DCF, diclofenac; DEX-P, dexamethasone sodium phosphate; DMARDs, disease-modifying anti-rheumatic drugs; DMM, destabilization of medial meniscus; Dex/Oxi-α CDNPs, 4-phenylborate-cyclodextrin biomaterial loaded with dexamethasone; ECM, extracellular matrix; ELP, elastin-like peptide; ERK1/2, extracellular signal-regulated kinase 1/2; FLSS, fibroblast synovial cells; GPX, glutathione peroxidase; GSH, glutathione; HA, hyaluronic acid; HIFU, high intensity focused ultrasound; HM, hollow microsphere; IBU, ibuprofen; IGF-1, insulin-like growth factor-1; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; Inflammatory arthritis; K/BxN, the T cell receptor transgene KRN and the MHC class II molecule; KAFAK, KAFAKLAARLYRKALARQLGVAA; KGN, kartogenin; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MFGCN, methotrexate-loaded folate-conjugated glycol chitosan nanoparticles; MHC, major histocompatibility complex; MMPs, matrix metalloproteinases; MNPs, multifunctional nanoparticles; MOF, metal-organic framework; MP-HANPs, mineralized nanoparticles; MPEG-PPF, methoxy polyethylene glycol-polypropylene fumarate; MRI, magnetic resonance imaging; MTX, methotrexate; NADPH, nicotinamide adenine dinucleotide phosphate; NFATc1, nuclear factor of activated T cell cytoplasmic 1; NGPEGSS, nanoparticles with degradable disulfide crosslinks; NIR, near-infrared; NO, nitric oxide; NP, nanoparticle; NP-gel, nanoparticle-hydrogel hybrid system; NSAIDs, non-steroidal anti-inflammatory drugs; Nrf2, nuclear factor erythroid 2-related factor 2; OA, osteoarthritis; P-HA, polyethylene glycol hyaluronic acid; PAMAM, poly (Ninylisobutyramide); PCA, protocatechuic acid; PDEPT, pre-enzyme drug therapy; PDT, photodynamic therapy; PEG-PLGA-Au, polyethylene-glycol polylactic-glycolic acid gold-containing nanoparticles; PEOx-PPOy-PEOz, poly (ethylene oxide)-block-poly (Oxypropylene)-block-poly (ethylene oxide); PEVS, platelet-derived extracellular vesicles; PICsomes, polyion complex vesicles; PLCG1, phospholipase C gamma 1; PLGA, polylactic-glycolic acid; PMEOMA, poly [2-(2-methoxyethoxy) ethylmethacrylate]; PNC, bisphosphonate-modified nanocellulose; PNIPAM, poly (N-isopropyl acrylamide); PON1, paraoxonase-1; POxs, poly (2-oxazoline); PPS, polyphenylene sulfide; PTH, parathyroid hormone; PTT, photothermal therapy; Q, a tripeptide sequence QAW; RA, rheumatoid arthritis; RANKL, nuclear factor-kappa B ligand; RFA, radiofrequency thermal ablation; RGD, arginine-glycine-aspartic acid; RMTQ, RGD-MMP-TAT-QAW peptide; ROS, reactive oxygen species; Redox, reduction-oxidation; SBC, sodium bicarbonate; SOD, superoxide dismutase; SPION, superparamagnetic iron oxide nanoparticles; Stimuli-responsive drug delivery system; Subchondral bone destruction; Synovitis; T cell, thymus cell; T, cell-penetrating peptide; TA, triamcinolone acetonide; TAT, transcription-transactivating; TATQ, TAT-QAW; TG-18, triglycerol monostearate; TIMP, tissue inhibitor of metalloproteinase; TNF, tumor necrosis factor; TR1, type 1 regulatory; TolDex, tolerogenic dendritic cell-derived exosomes; US, ultrasound; VEGF, vascular endothelial growth factor; fMRI, focusing magnetic resonance imaging; β-TCP, β-tricalcium phosphate.