Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1β induced inflammation in synoviocytes in�vitro

Abstract

Osteoarthritis (OA) is a common degenerative joint disease characterized by inflammation of synoviocytes and degradation of cartilage. In the present study, hyaluronic acid/chitosan (HA/CS) nanoparticles were used as a vehicle for gene therapy of OA, and the cytokine response modifier A (CrmA) pDNA was proposed as the target gene. The HA/CS/pCrmA nanoparticles were prepared and the characteristics of the nanoparticles were examined. The nanoparticles were spherical, and the smallest size was obtained with the HA:CS weight ratio of 1:4. The release analysis exhibited a constant release over 29 days. The pDNA was completely combined with HA/CS nanoparticles and the HA/CS nanoparticles protected pDNA from degradation. Subsequently, rat synoviocytes were transfected with HA/CS/pDNA nanoparticles, and the results demonstrated that the HA/CS nanoparticles were able to improve the transfection capacity of pDNA. The cytotoxicity of the HA/CS/pDNA nanoparticles was additionally detected using a MTS assay to ensure that the HA/CS nanoparticle was a safe carrier. To additionally investigate the effects of HA/CS/pCrmA nanoparticles on synoviocytes in OA, the MMP-3 and MMP-13 gene expression levels were detected at the gene and protein expression levels. These results indicated that the HA/CS/pCrmA nanoparticles attenuated interleukin-1β-mediated inflammation in synoviocytes. It was concluded that the HA/CS/pCrmA nanoparticles may provide a novel approach to the treatment of OA.

Electrospun Fibres with Hyaluronic Acid-Chitosan Nanoparticles Produced by a Portable Device

“…Nanoparticles are particularly interesting for biomedical applications, mainly because they offer high encapsulation efficiency, are able to penetrate tissues, usually have a slow degradation rate, have a small mean size, and effective targetability [ 36 ]. HA-CS nanoparticles have been used for a number of clinical applications, including protein and drug delivery [ 26 ], contrast agents and macromolecule carriers [ 27 , 37 , 38 ]. These nanoparticles are particularly useful for tissue engineering applications, as they interact well with cell surfaces and offer prolonged residence time at the target site [ 35 ].…”

“…Nanoparticles offer high encapsulation efficiency and penetration ability, slow degradation rate, small mean size (10–1000 nm) and effective targetability [ 36 ]; characteristics that are particularly useful for biomedical applications. Clinical applications of HA-CS NPs include non-viral vectors for gene delivery [ 26 ], protein or drug delivery [ 33 ], tumour-targeted magnetic resonance imaging (MRI) contrast agents and macromolecule micro/nanocarriers [ 27 ] with controlled release, including heparin [ 35 ], interleukin (IL)-1β [ 37 ], DNA and RNA [ 38 ].…”

Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican

“…HA production by synovium derived cell cultures from either OA or RA patients have been extensively studied in connection with the production of inflammatory molecules and therapeutic interventions with a variety of small molecule drugs [ 70 , 71 , 72 ] to control inflammation in a range of arthritic conditions. Furthermore, such cells have been used to examine the effect of potential therapeutic HA formulations [ 73 ].…”

Biomedical applications of polysaccharide nanoparticles for chronic inflammatory disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis

“…Therapeutic agents allow encapsulating within the NPs that aid in modifying the drug J o u r n a l P r e -p r o o f pharmacokinetic, biological distribution and site-specific release of the targeted drug [124,125].…”