Anti-inflammatory activity of polyamide dendrimers bearing bile acid termini synthesized via SPAAC
Autor: | Ana M. Garzón-Porras, Kurt Lucas, Diego L. Bertuzzi, Catia Ornelas |
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Rok vydání: | 2019 |
Předmět: |
Materials science
medicine.drug_class Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences chemistry.chemical_compound Chenodeoxycholic acid Dendrimer medicine General Materials Science Cytotoxicity Bile acid Cholic acid General Chemistry 021001 nanoscience & nanotechnology Condensed Matter Physics Combinatorial chemistry Atomic and Molecular Physics and Optics Ursodeoxycholic acid 0104 chemical sciences chemistry Modeling and Simulation Drug delivery Azide 0210 nano-technology medicine.drug |
Zdroj: | Journal of Nanoparticle Research. 21 |
ISSN: | 1572-896X 1388-0764 |
Popis: | Inflammation is a general pathomechanism associated with numerous diseases of global impact such as many cancers, metabolic disorders, and neurodegenerative and autoimmune diseases. The development of drugs that can treat chronic inflammation, in an effective way and that are well tolerated by the patients, is an active research area that pursues the treatment for hundreds of diseases. Dendrimers recently appeared as a convenient starting point for the design of anti-inflammatory drugs due to its nanosize, well-defined branched structure, multivalency, and versatility. In this work, polyamide dendrimers with 1 ➔ 3 connectivity were synthesized and functionalized with three types of bile acids (BAs): cholic acid (CA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA). Functionalization was carried out through strain-promoted alkyne–azide cycloaddition (SPAAC) between an azide dendrimer and cyclooctyne derivatives of bile acids. The cell viability and the anti-inflammatory potential of the bile acid dendrimers were evaluated in vitro and compared with those of the pure BAs. The bile acid dendrimers and pure BAs did not show significant cytotoxicity at the concentrations tested (0.78–5.00 × 104 nM) against THP-1 cells. Chenodeoxycholic acid (CDCA) and the corresponding dendrimer dendri-(CDCA)18 (polyamide dendrimer bearing 18 CDCA moieties) presented the highest anti-inflammatory activity, showing LPS-induced IL-8 release inhibition of 45.3% at 0.78 nM CDCA and 35.5% at 0.43 nM dendri-(CDCA)18. |
Databáze: | OpenAIRE |
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