Biodegradable Dextran Sulfate-graft-methotrexate Development
Dextran sulfate-graft-methotrexate conjugate (DS-g-MTX) has shown a broad prospect in targeted therapy of rheumatoid arthritis (RA). CD BioGlyco is committed to providing clients with professional solutions to generate this coupling compound with precise chemical structure, accelerating the development of MTX-based RA therapy.
Methotrexate-based Therapy for RA
RA is a chronic autoimmune disease related to genetic sensitivity, environmental factors, infection, sex hormones, and other factors. Activated macrophages are widely believed to be key effectors in the development of RA, leading to prolonged periods of inflammation and exacerbation of affected joints. As the major cell population in the synovium of RA, activated macrophages have many specifically expressed receptors, such as the folate receptor (FR) and the scavenger receptor (SR). Therefore, activated macrophages have become the primary target for active targeting therapy of RA.
MTX has been the main drug in the treatment of RA for the past 20 years and has an excellent inhibitory effect on the production of pro-inflammatory cytokines. However, some patients exhibited tolerance to the drug and severe side effects. One strategy to overcome this challenge is to develop nanocarriers for MTX to achieve the specific delivery of MTX to lesion cells and obstruction of drug uptake by normal cells. DS-based nanoparticles perform well in efficiently reaching inflamed joints through active and passive targeting mechanisms, making them ideal drug carriers for RA therapy.
Fig.1 Schematic illustration of synthesis, intravenous administration, targeted delivery, and brief mechanism of Dex-g-MTX/FA in the treatment of collagen-induced arthritis (CIA). (Yang, et al., 2016)
Biodegradable DS-g-MTX Development Services at CD BioGlyco
Our researchers are committed to providing clients with the development of Dextran-based Biodegradable Materials, such as dextran-methotrexate conjugate. Dextran sulfate (DS) has received extensive attention in the development of drugs for the treatment of RA due to its ability to selectively bind to class A SRs through ligand-receptor recognition. To efficiently deliver MTX to inflamed joints in RA, we have developed comprehensive solutions to help clients prepare DS-g-MTX. Our services include but are not limited to:
- Preparation of DS nanoparticles (DSNPs)
We help our clients develop nanoscale carriers that efficiently accumulate in inflamed joints and release MTX within target cells.
- Preparation of drug-loaded nanoparticles
We used 1-ethyl-(3-(dimethylamino)propyl)carbodiimide hydrochloride (EDC·HCl) as the condensing agent and 4-N,N-dimethylaminopyridine (DMAP) as the catalyst to help clients synthesize macrophage-targeted DS-g-MTX and untargeted dextran-methotrexate prodrug (Dex-g-MTX).
- Characterization of DSNPs and DS-g-MTX
We offer a variety of techniques such as proton nuclear magnetic resonance (1H NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and transmission electron microscopy to help clients characterize nanocarriers and conjugates. Moreover, we offer biocompatibility testing via spectroscopy.
Our Advantages
- Efficient and high-precision synthesis scheme
- Comprehensive and systematic detection and characterization
- Customize experimental schemes according to different research needs
- Considerable savings and short experimental cycle time
CD BioGlyco has accumulated rich experience in developing a variety of Polysaccharide-based Biodegradable Materials. We have the strength to provide clients with professional solutions and technical support for developing DS-g-MTX to improve the therapeutic effect of MTX.
If you are interested in our business, please feel free to contact us for more details, and we will respond promptly.
Reference
- Yang, M.; et al. Activated macrophage-targeted dextran-methotrexate/folate conjugate prevents deterioration of collagen-induced arthritis in mice. Journal of Materials Chemistry B. 2016, 4(12): 2102-2113.
