Nanomedicines for the delivery of glucocorticoids and nucleic acids as potential alternatives in the treatment of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects 0.5 to 1% of the world population. Current treatments include on one hand non-steroidal anti-inflammatory drugs and glucocorticoids (GCs) for treating pain and on the other hand disease-modifying anti-rheumatic drugs such as methotrexate, Janus kinase inhibitors or biologics such as antibodies targeting mainly cytokine expression. More recently, nucleic acids such as siRNA, miRNA or anti-miRNA have shown strong potentialities for the treatment of RA. This review discusses the way nanomedicines can target GCs and nucleic acids to inflammatory sites, increase drug penetration within inflammatory cells, achieve better subcellular distribution and finally protect drugs against degradation. For GCs such a targeting effect would allow the treatment to be more effective at lower doses and to reduce the administration frequency as well as to induce much fewer side-effects. In the case of nucleic acids, particularly siRNA, knocking down proteins involved in RA, could importantly be facilitated using nanomedicines. Finally, the combination of both siRNA and GCs in the same carrier allowed for the same cell to target both the GCs receptor as well as any other signaling pathway involved in RA. Nanomedicines appear to be very promising for the delivery of conventional and novel drugs in RA therapeutics.

Nanomaterials for the Diagnosis and Treatment of Inflammatory Arthritis

“…Modification of NPs via PEGylation, a process of covalent conjugation that prevents removal from the reticuloendothelial system, or via conjugation with other small molecules (peptides, vitamins, and antibodies) can greatly prolong the circulation time of the systems in the blood and improve the efficacy of the anti-RA drug being delivered, such as NSAIDs, corticosteroids, DMARDs, small interfering RNAs (siRNAs), and therapeutic peptides [132]. Synthetic cationic polymers such as polyethylenemine (PEI), poly-L-lysine (PLL), and dendrimers are usually utilized to deliver nucleic acids such as DNA and interfering RNAs (RNAi) [133]. Among them, PEI is the most frequently employed because of numerous protonated amino functional groups, allowing for a higher cationic charge density at physiological pH that facilitates the attachment of nucleic acids via electrostatic adsorption [133].…”

“…Synthetic cationic polymers such as polyethylenemine (PEI), poly-L-lysine (PLL), and dendrimers are usually utilized to deliver nucleic acids such as DNA and interfering RNAs (RNAi) [133]. Among them, PEI is the most frequently employed because of numerous protonated amino functional groups, allowing for a higher cationic charge density at physiological pH that facilitates the attachment of nucleic acids via electrostatic adsorption [133].…”

Dexamethasone Conjugates: Synthetic Approaches and Medical Prospects

“…The administration of drugs using extended release delivery systems can control the release and increase the residence time of the drug at the target site, thereby reducing the frequency of doses and the risk of side effects [7][8][9][10][11][12]. For this reason, much research is focused on the development of DEX delivery systems with a release profile that extends from several days to months [13].…”

“…Many reviews have appeared recently on DEX delivery systems [15,16], especially those aimed at ocular [7,17] and intra-articular [8] therapies. These reviews have discussed DEX delivery using many nanocarriers, including polymer and lipid particles, dendrimers, micelles, liposomes, implants, and conjugates.…”

Nanomedicine Strategies for Anti‐Inflammatory Treatment of Noninfectious Arthritis

“…[4] In recent years, other therapeutic modalities, such as gene medicine based on siRNA and miRNA, have also been proposed in conjunction with nanoparticle platforms for treating NIA. [5] Here, we first review the mechanisms and pathogenesis of four common forms of NIA and discuss the current clinical antiinflammatory treatments and their limitations. We then describe recent advances in the development of nanomedicine platforms for NIA treatment.…”