scholarly journals Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shujing Ren ◽  
Heng Liu ◽  
Xitong Wang ◽  
Jiquan Bi ◽  
Shengfeng Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Targeted Delivery ◽  
Bone Erosion ◽  
Treg Cells ◽  
Modern Medicine ◽  
Inflammatory Factors ◽  
Nanocomposite Hydrogel ◽  
Analgesic Effects ◽  
Anti Inflammatory

Abstract Background Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). Results We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. Conclusion This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine. Graphical Abstract

scholarly journals Acupoint Nanocomposite Hydrogel for Simulation of Acupuncture and Targeted Delivery of Triptolide Against Rheumatoid Arthritis

2021 ◽  
Author(s):  
Shujing Ren ◽  
Heng Liu ◽  
Xitong Wang ◽  
Jiquan Bi ◽  
Shengfeng Lu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Targeted Delivery ◽  
Pain Threshold ◽  
Modern Medicine ◽  
Inflammatory Factors ◽  
Nanocomposite Hydrogel ◽  
Analgesic Effects ◽  
Anti Inflammatory ◽  
Targeting Ability

Abstract BackgroundAttenuating the inflammatory response and relieving pain are two therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with effective targeting ability and other complementary strategies are on urgent need to be explored. To achieve this goal, an acupoint drug delivery system that can simulate acupuncture in relieving pain and targeted deliver anti-inflammatory drugs is constructed, which can co-deliver 2-chloro-N (6)-cyclopentyl adenosine (CCPA) and triptolide (TP). ResultsWe have successfully demonstrated that the nanocomposite hydrogel composed of TP-Human serum album nanoparticles (HSA NPs) and CCPA could effectively treat the RA. We found that this combination therapy can enhance analgesic effects while the mechanical pain threshold was 5.2 times compared with model group, and the thermal pain threshold was 1.4 times. Acupoint nanocomposite hydrogel could not only improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48h), but also cooperate with nanomedicine to exert synergetic improvement of inflammation and reduction of systemic toxicity. Furthermore, it can regulate inflammatory factors and restore the balance of Th17/Treg cell which provide a novel effective treatment strategy for RA.ConclusionThis novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

Therapeutic Properties of PDMS Nanoparticles: A Promising New Drug Delivery Vehicle Against Inflammatory Conditions

2021 ◽  
Vol 24 ◽  
Author(s):  
Aiswarya Anilkumar Ajitha ◽  
Sri SivaKumar ◽  
Gayathri Viswanathan ◽  
Sabulal Baby ◽  
Prabath Gopalakrishnan Biju
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Release Kinetics ◽  
Drug Loading ◽  
Systemic Circulation ◽  
Biological Evaluation ◽  
Raw 264.7 Cells ◽  
Morphological Examination ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

Background: Over the last few decades, there has been a stupendous change in the area of drug delivery using particulate delivery systems, with increasing focus on nanoparticles in recent times. Nanoparticles helps to improve and alter the pharmacodynamic properties and pharmacokinetics of various types of drug molecules. These features help to protect the drug entity in the systemic circulation, access of the drug to the chosen sites, and to deliver the drug in a controlled and sustained rate at the site of action. Objective: Nanoparticle based targeted delivery of anti-inflammatory drugs/signal modulatory agents to the cytoplasm or nuclei of the targeted cell can significantly enhance the precision and efficacy of intended therapeutic activity. To this end, we report ligand free, enhanced intra-nuclear delivery model of anti-inflammatory therapeutics via PDMS nanoparticles. Method: PDMS nanoparticles were prepared by sacrificial silica template-based approach and details of their characterization for suitability as a nanoparticle-based delivery material is detailed herein. Results: Biological evaluation for compatibility was carried out and the results showed that the PDMS nanoparticle has no toxicity on RAW 264.7 cells in the concentration range of 10, 20, 40, 60, 80, 100 and 120 μg/mL in culture. Biocompatibility and absence of toxicity was determined by morphological examination and cell viability assays. Drug loading and release kinetics were carried out with the anti-inflammatory drug Diclofenac. Conclusion: In this paper we clearly demonstrate the various aspects of nanoparticle articulation, characterization, effect of their characteristics and their applications as a non-toxic drug delivery molecule for its potential applications in therapeutic delivery of drugs for sustained release.

scholarly journals Knockdown adiponectin receptor 1 expression in synovial tissue alleviate the progression of collagen-induced arthritis

2019 ◽  
Author(s):  
Yani Wang ◽  
Rui Liu ◽  
Pengfei Zhao ◽  
Qian Zhang ◽  
Yingheng Huang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Bone Erosion ◽  
Adiponectin Receptor ◽  
Inflammatory Factors ◽  
Nuclear Factor ◽  
Collagen Induced Arthritis ◽  
Adiponectin Receptor 1 ◽  
Receptor Activator

Abstract Background: Previous studies have shown that adiponectin (APN) is involved in the pathogenesis of rheumatoid arthritis (RA). The proinflammatory effect of APN is mainly mediated adiponectin receptor 1 (AdipoR1). The high expression of AdipoR1 have been suggested in RA synovial tissue. This study was aimed to investigate the effects of AdipoR1 in inflammation and bone erosion in collagen-induced arthritis (CIA) mice, and to further explore the underlying mechanisms. Methods: The expression of APN and AdipoR1 in synovial tissue of RA and osteoarthritis (OA) patient was tested by qPCR and western blot. RA synovial fibroblasts (RASFs) were stimulated with APN, IL-6 or TNF-α respectively. The expression of AdipoR1 on RASFs were tested by flow cytometry. To prove the pathogenic role, AdipoR1 was silenced in a human rheumatoid arthritis synovial fibroblast cell line (MH7A) and local joint of CIA mice by specific short hairpin RNAs (shRNAs) using a lentiviral delivery system. The levels of proliferation, apoptosis and inflammatory factors on MH7A were assessed in vitro. Local AdipoR1 knockdown on CIA mice were further estimated by arthritis clinical scores, inflammatory cytokine expression, micro-CT, H&E staining and receptor activator of nuclear factor к B ligand (RANKL) / osteoprotegerin (OPG) in vivo. Results: We found that the levels of APN and AdipoR1 expression were significantly higher in RASFs and the expression of AdipoR1 was upregulated by APN in RASFs. Silencing AdipoR1 could effectively reduce lipopolysaccharides (LPS) induced proliferation of MH7A cells, promote their apoptosis, and reduce the release of inflammatory factors. In CIA mice, local silencing AdipoR1 in arthritis markedly reduced joint inflammation and alleviated bone erosion and osteoporosis in vivo. Furthermore, local silencing AdipoR1 inhibited receptor activator of nuclear factor к B ligand (RANKL) expression and decreased RANKL / osteoprotegerin (OPG) ratio in knees and ankles of CIA mice. Conclusions: This study suggests that AdipoR1 plays a key role in the development of RA and silencing AdipoR1 might be a new target for the clinical treatment of RA.

Cytokines and miRNAs in the Pathogenesis of Rheumatoid Arthritis: A Review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yu Z ◽  
◽  
Hu Y ◽  
Liu H ◽  
Fan J ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Inflammatory Cytokines ◽  
Treg Cells ◽  
Th Cells ◽  
Synovial Hyperplasia ◽  
Initial Stage ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Chronic Autoimmune Disease

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by inflammatory synovial hyperplasia. The pathogenesis of RA may be related to heredity, infection and sex hormones. The initial stage of RA involves the activation of T cells. Immature CD4+ T cells differentiate into T helper (Th) cells and T regulatory (Treg) cells under antigen stimulation and cytokine signal transduction. Cytokines secreted by Th cells and Treg cells play crucial roles in the pathophysiology of RA. The cytokines can be roughly divided into proinflammatory cytokines, anti-inflammatory cytokines, and both pro- and antiinflammatory cytokines. The imbalance between pro-inflammatory cytokines and anti-inflammatory cytokines would lead to a variety of autoimmune diseases. The disease severity was significantly indicated by serum or plasma cytokine levels with RA patients. Many clinical trials have shown that anticytokine drugs are effective in treating RA. This article reviews the differentiation process of different Th cells and Treg cells, the roles of cytokines secreted by them in the pathogenesis of RA and how miRNAs mediate immune regulation in RA. By understanding the roles of cytokines and miRNAs in the pathogenesis of autoimmunity, it is necessary to develop potential anti-cytokine drugs and biomarkers/therapeutic targeted drugs through various ways in the treatment of RA.

scholarly journals Localized and targeted delivery of NSAIDs for treatment of inflammation: A review

2018 ◽  
Vol 244 (6) ◽  
pp. 433-444 ◽  
Author(s):  
Rebecca M Haley ◽  
Horst A von Recum
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Local Drug Delivery ◽  
Future Research ◽  
Systemic Delivery ◽  
Number Of Patients ◽  
Long Term Treatment ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Inflammatory processes are increasingly being identified at the core of many different disease states (e.g. heart disease, cancer, diabetes). As such, anti-inflammatory strategies available through drug delivery have undergone renewed interest. Due to the systemic side effects of steroidal drugs, non-steroidal anti-inflammatory drugs are often preferred for long-term treatment of inflammation in a variety of applications. While non-steroidal anti-inflammatory drugs are generally safe, there are some serious side effects that can be associated with their usage, particularly when given systemically or orally. Due to the high number of patients taking non-steroidal anti-inflammatory drugs, the reduction or elimination of these side effects, such as is possible through local drug delivery, could have a very powerful effect on patient quality of life. This review comments on a sampling of existing methods for localized or targeted delivery of non-steroidal anti-inflammatory drugs, with the goal of helping future research groups to focus on bettering methods shown to be effective and filling the gaps of knowledge in this field. Additionally, commentary is made on the field as a whole, and the standardization issues that arise from its expansiveness and diversity. Impact statement This work provides an overview of research currently being done exploring potential drug delivery device strategies for NSAIDs as an alternative to systemic delivery. Commentary on this field is made in an attempt to aid future experimental design, enabling researchers to determine the drugs and delivery vehicles which are most advantageous for them to pursue, as well as suggestions to standardize the reporting of such future research.

scholarly journals Inhibition of Rheumatoid Arthritis Using Bark, Leaf, and Male Flower Extracts of Eucommia ulmoides

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Yun-Yun Xing ◽  
Jian-Ying Wang ◽  
Kai Wang ◽  
Yan Zhang ◽  
Kun Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Male Flower ◽  
Joint Inflammation ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Eucommia Ulmoides

Eucommia ulmoides Oliv., a native Chinese plant species, has been used as a traditional Chinese medicine formulation to treat rheumatoid arthritis (RA), strengthen bones and muscles, and lower blood pressure. Various parts of this plant such as the bark, leaves, and flowers have been found to have anti-inflammatory properties. E. ulmoides has potential applications as a therapeutic agent against bone disorders, which were investigated in this study. In vitro, RA joint fibroblast-like synoviocytes (RA-FLS) were treated with different concentrations (0, 25, 50, 100, 200, 400, 800, and 1000 μg/mL) of E. ulmoides bark, leaf, and male flower alcoholic extracts (EB, EL, and EF, respectively) to determine their potential cytotoxicity. Tumor necrosis factor- (TNF-) α and nitric oxide (NO) levels in RA-FLS were quantified using enzyme-linked immunosorbent assay (ELISA). Furthermore, collagen-induced arthritis (CIA) rats were treated with EB, EL, EF, Tripterygium wilfordii polyglycoside (TG) or the normal control (Nor), and then ankle joint pathology, bone morphology, and serum and spleen inflammatory cytokine levels were evaluated. The results showed that, in RA-FLS, EB, EL, and EF were not cytotoxic; EB and EF reduced TNF-α supernatant levels; and EB, EL, and EF reduced NO levels. The results of in vivo experiments showed that EB, EL, and EF alleviated ankle swelling and joint inflammation, while all extracts diminished inflammatory cell infiltration, pannus and bone destruction, and bone erosion. All tested extracts inhibited interleukin- (IL-) 6, IL-17, and TNF-α mRNA in the spleen of CIA rats, while EB most effectively reduced osteoclasts and inhibited bone erosion. EF showed the most obvious inhibition of inflammatory factors and pannus. Thus, EB, EL, and EF may alleviate bone destruction by inhibiting inflammation.

scholarly journals The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis

2020 ◽  
Vol 92 (6) ◽  
pp. 46-52
Author(s):  
Natalya V. Chebotareva ◽  
Anatoly A. Vinogradov ◽  
Alla A. Gindis ◽  
Irina N. Bobkova ◽  
Wenjing Cao ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Kidney Tissue ◽  
Treg Cells ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Chronic Glomerulonephritis ◽  
Clinical Activity ◽  
Group I ◽  
Anti Inflammatory

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression. Aim. To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). Materials and methods. The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). Results. In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. Conclusion. An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

scholarly journals Green Synthesis of Gold and Iron Nanoparticles for Targeted Delivery: An In Vitro and In Vivo Study

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Beenish Khanzada ◽  
Nosheen Akthar ◽  
Muhammad Zeeshan Bhatti ◽  
Hammad Ismail ◽  
Mohammed Alqarni ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Medicinal Plants ◽  
Targeted Delivery ◽  
Iron Nanoparticles ◽  
Drug Loading ◽  
Research Work ◽  
Ficus Microcarpa ◽  
Anti Inflammatory

Nanotechnology has vast applications in almost all fields of science and technology. The use of medicinal plants for the synthesis of metallic nanoparticles has gained much attention nowadays. In the current research work, six medicinal plants were used for the synthesis of gold nanoparticles (AuNPs) and iron nanoparticles (FeNPs). The synthesized nanoparticles were characterized by different techniques including UV-visible spectrophotometry, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). Furthermore, the activities of green synthesized nanoparticles were screened in vitro using, for example, antibacterial, antioxidant, cytotoxic, and DNA protection assays. Both FeNPs and AuNPs had spherical shapes with an average size less than 50 nm and were found to have good antimicrobial and nontoxic effects. Furthermore, FeNPs from Ficus microcarpa demonstrated high drug loading efficiency (65%) as compared to an anti-inflammatory drug (diclofenac potassium, DFP). We also evaluated the drug delivery potential, as well as anti-inflammatory and anticoagulant properties, of nanoparticles in vivo. Interestingly, AuNPs of Syzygium cumini exhibited strong anti-inflammatory potential as compared to DFP and diclofenac-loaded FeNPs of Ficus microcarpa. The results suggest potential pharmacological applications of biogenic synthesized AuNPs and FeNPs which can be explored further. The study revealed that the green synthesized AuNPs and FeNPs provide a promising approach for the synthesis of drug-loaded nanoparticles and consequently in the field of targeted drug delivery.

Targeted drug-delivery systems in the treatment of rheumatoid arthritis: recent advancement and clinical status

2020 ◽  
Vol 11 (4) ◽  
pp. 269-284 ◽  
Author(s):  
Srividya Gorantla ◽  
Gautam Singhvi ◽  
Vamshi Krishna Rapalli ◽  
Tejashree Waghule ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Bone Erosion ◽  
Folate Receptor ◽  
Clinical Status ◽  
Joint Destruction ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Systemic Autoimmune Disease

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is characterized by synovial inflammation, cellular infiltration in joints which leads to progressive joint destruction and bone erosion. RA is associated with many comorbidities including pulmonary disease, rheumatoid nodules and can have a pessimistic impact on quality of life. The current therapies of RA treatment comprise conventional, small molecule and biological antirheumatic drugs. Their utility as therapeutic agents is limited because of poor absorption, rapid metabolism and adverse effects (dose-escalation, systemic toxicity, lack of selectivity and safety). To overcome these limitations, the novel drug delivery systems are being investigated. This review has compiled currently approved therapies along with emerging advanced drug-delivery systems for RA treatment. Further, active targeting of therapeutic agents to inflamed joints via folate receptor, CD44, angiogenesis, integrins and other provided an improved therapeutic efficacy in the treatment of RA.

scholarly journals Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment

2021 ◽  
Vol 9 ◽  
Author(s):  
Huailan Wang ◽  
Yunxiang Zhou ◽  
Qunan Sun ◽  
Chenghao Zhou ◽  
Shiyao Hu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Inflammatory Bowel Disease ◽  
Drug Delivery Systems ◽  
Inflammatory Diseases ◽  
Future Perspective ◽  
Efficient Delivery ◽  
Inflammatory Bowel ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Nanobiotechnology plays an important role in drug delivery, and various kinds of nanoparticles have demonstrated new properties, which may provide opportunities in clinical treatment. Nanoparticle-mediated drug delivery systems have been used in anti-inflammatory therapies. Diseases, such as inflammatory bowel disease, rheumatoid arthritis, and osteoarthritis have been widely impacted by the pathogenesis of inflammation. Efficient delivery of anti-inflammatory drugs can reduce medical dosage and improve therapeutic effect. In this review, we discuss nanoparticles with potential anti-inflammatory activity, and we present a future perspective regarding the application of nanomedicine in inflammatory diseases.

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