scholarly journals Construction of a Nano-Controlled Release Methotrexate Delivery System for the Treatment of Rheumatoid Arthritis by Local Percutaneous Administration

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2812
Author(s):  
Tingting Guo ◽  
Xu Kang ◽  
Sifan Ren ◽  
Xianjin Ouyang ◽  
Mingming Chang
Keyword(s):  
Rheumatoid Arthritis ◽  
Controlled Release ◽  
Delivery System ◽  
Initial Level ◽  
In Vivo Experiments ◽  
Cumulative Amount ◽  
Group Experiences ◽  
Percutaneous Administration

A drug delivery system was specifically designed for the treatment of rheumatoid arthritis (RA) by local percutaneous administration and the nano-controlled release of methotrexate (MTX). The release behavior of MTX from the synthesized MTX-mSiO2@PDA system was investigated in vitro and in vivo. The obtained results show that after 48 h, twice as much MTX (cumulative amount) is released at pH 5.5 than at pH 7.4. This suggests that the MTX-mSiO2@PDA system exhibits a good pH sensitivity. In vitro local percutaneous administration experiments revealed that the cumulative amount of MTX transferred from MTX-mSiO2@PDA to pH 5.0 receptor fluid through the whole skin was approximately three times greater than the amount transferred to pH 7.4 receptor fluid after 24 h. Moreover, in vivo experiments conducted on a complete induced arthritis (CIA) model in DBA/1 mice demonstrated that the thickness of a mouse’s toes decreases to nearly 65% of the initial level after 27 days of local percutaneous MTX-mSiO2@PDA administration. Compared to the mice directly injected with MTX, those administered with MTX-mSiO2@PDA by local percutaneous application exhibit much lower toe thickness deviation, which indicates that the latter group experiences a better cure stability. Overall, these results demonstrate that the local percutaneous administration of MTX delivery systems characterized by nano-controlled release may play an important role in RA therapy.

Angiotensins and rheumatoid arthritis

2019 ◽  
Vol 56 (6) ◽  
pp. 753-759
Author(s):  
N. M. Savushkina ◽  
E. A. Galushko ◽  
N. V. Demidova ◽  
A. V. Gordeev
Keyword(s):  
Rheumatoid Arthritis ◽  
Enzyme Inhibitors ◽  
Renin Angiotensin System ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
The Body ◽  
Converting Enzyme Inhibitors ◽  
In Vivo Experiments ◽  
Endothelial Growth Factor

At present, the role of the renin-angiotensin system (RAS) in regulating the cardiovascular system and maintaining water and electrolyte homeostasis has been well studied. However, over the past decades, new components of the RAS have been identified, suggesting a wider range of its potential effects on the body. It is of fundamentally importance for rheumatologists to affect inflammation, including rheumatoid inflammation, through blockade of angiotensin (AT) II formation via the effects of AT 1–7 and angiotensin-converting enzyme inhibitors, as well as through suppression of angiogenesis, primarily by reducing the production of endothelial growth factor. The organ-protective and antiinflammatory potential of drugs that reduce the production of AT, which has been proven in in vitro and in vivo experiments, allows us to consider them as first-line angiotropic agents in patients with rheumatoid arthritis, especially in the presence of concomitant hypertension and/or nephropathy.

scholarly journals Systemic Administration of miRNA Mimics by Liposomal Delivery System in Animal Model of Colorectal Carcinoma

2016 ◽  
pp. S481-S488 ◽  
Author(s):  
J. MERHAUTOVÁ ◽  
P. VYCHYTILOVÁ-FALTEJSKOVÁ ◽  
R. DEMLOVÁ ◽  
O. SLABÝ
Keyword(s):  
Delivery System ◽  
Tumor Volume ◽  
Human Cancer ◽  
Suppressive Effect ◽  
Systemic Administration ◽  
In Vivo Experiments ◽  
Nsg Mice ◽  
Liposomal Delivery

MiRNAs are important regulators of gene expression and changes in their levels are linked with various pathological states, including solid tumors. MiR-215 has been identified as a tumor suppressor in colorectal cancer (CRC). Following our previous in vitro and in vivo experiments, the aim of this project was to study the possibility of increasing the levels of miR-215 in tumor cells by systemic administration of miRNA mimics in liposomal delivery system in vivo. By subcutaneous xenotransplantation of human cancer cells to NSG mice, CRC model was established. The treatment [miR-215 mimics in liposomes (20 and 40 μg/mouse), control oligonucleotide in liposomes, or saline] was administered repeatedly by i.v. injection via tail-vein. Animals were sacrificed, tumor were dissected and measured by a caliper. Expression of miR-215 in tumors, lungs and liver was quantified by RT-PCR. There was no significant differences in tumor volume and miR-215 expression between all three treatment groups. Therefore, the decrease in tumor volume was not achieved. By comparing the levels of miR-215 in lungs, liver and tumors after the treatment, we suggest that the liposomes are accumulated in the lungs and do not concentrate sufficiently in the tumor site to exert significant tumor-suppressive effect.

scholarly journals Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

2020 ◽  
Author(s):  
Feili Yan ◽  
Zhirong Zhong ◽  
Yao Wang ◽  
Hui Li ◽  
Zhiqiang Mei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
Safety Evaluation ◽  
Biomimetic Nanoparticles ◽  
Term Administration

Abstract Backgroud: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was − 22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo pharmacodynamic experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility. Conclusion The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

Bosentan Monohydrate Vesicles Loaded Transdermal Drug Delivery System: In Vitro In Vivo Evaluation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Revathi M. ◽  
Indira Y.
Keyword(s):  
Controlled Release ◽  
Delivery System ◽  
Ex Vivo ◽  
In Vitro Release ◽  
In Vivo Studies ◽  
In Vivo Evaluation ◽  
Vitro Release ◽  
Transdermal Route

This study elucidates the enhancement of the permeation of bosentan monohydrate through skin by encapsulating it in vesicles loaded transdermal delivery system. Niosomal vesicles were formulated by ether injection method. Formulation FN7 (span 60: cholesterol: poloxamer 401, 1.25:1:0.25) showed maximum entrapment efficiency of 96.7±0.037% and was optimized for loading in to transdermal system. Transdermal systems were formulated using both hydrophilic and hydrophobic polymers like HPMC, HEC and EC. Formulation F1 with HPMC was optimized based on in vitro release (99.21±1.45 %) and was further evaluated for ex-vivo permeation. The results indicate that the ex vivo release (98.13±1.65%) was as par with in vitro release and followed zero order super case- II transport mechanism. The in vivo studies were done on New Zealand male rabbits for oral and transdermal route. The results inferred no significant change in half-life of drug but a substantial difference in Tmax, AUC and MRT was observed in transdermal systems. A two fold increase in AUC was observed in transdermal route (18.609±7.251µg/ml/h) when compared to oral route (9.644±5.621µg/ml/h). A controlled release was attained up to 35h and reservoir effect was observed and this may be due to the barrier properties of skin. Drug encapsulated niosomes were released in to the skin by loosening the lipid layers and the surfactant acted as penetration enhancer. The study infers that niosomes loaded transdermal patches of bosentan monohydrate can enhance the bioavailability and provided controlled release for better therapeutic efficacy and safety of drug.

scholarly journals Exosome-based biomimetic nanoparticles targeted to inflamed joints for enhanced treatment of rheumatoid arthritis

2020 ◽  
Author(s):  
Feili Yan ◽  
Zhirong Zhong ◽  
Yao Wang ◽  
Yue Feng ◽  
Zhiqiang Mei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
Safety Evaluation ◽  
Biomimetic Nanoparticles ◽  
Term Administration

Abstract Background: Glucocorticoids (GCs) show powerful treatment effect on rheumatoid arthritis (RA). However, the clinical application is limited by their nonspecific distribution after systemic administration and serious adverse reactions during long-term administration. To achieve better treatment and reduce side effect, we here established a biomimetic exosome (Exo) encapsulating dexamethasone sodium phosphate (Dex) nanoparticle (Exo/Dex), whose surface was modified with folic acid (FA)-polyethylene glycol (PEG)-cholesterol (Chol) compound to attain FPC-Exo/Dex active targeting drug delivery system. Results: The size of FPC-Exo/Dex was 128.43 ± 16.27 nm, with a polydispersity index (PDI) of 0.36 ± 0.05, and the Zeta potential was -22.73 ± 0.91 mV. The encapsulation efficiency (EE) of the preparation was 10.26 ± 0.73%, with drug loading efficiency (DLE) of 18.81 ± 2.05%. In vitro study showed this system displayed enhanced endocytosis and excellent anti-inflammation effect against RAW264.7 cells by suppressing pro-inflammatory cytokines and increasing anti-inflammatory cytokine. Further biodistribution study showed the fluorescence intensity of FPC-Exo/Dex was stronger than other Dex formulations in joints, suggesting its enhanced accumulation to inflammation sites. In vivo biodistribution experiment displayed FPC-Exo/Dex could preserve the bone and cartilage of CIA mice better and significantly reduce inflamed joints. Next in vivo safety evaluation demonstrated this biomimetic drug delivery system had no obvious hepatotoxicity and exhibited desirable biocompatibility.Conclusion: The present study provides a promising strategy for using exosome as nanocarrier to enhance the therapeutic effect of GCs against RA.

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