Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines
| Autor: | Khaled Yehia Farroh, Samah A. Loutfy, Ahmed Hassan Ibrahim Faraag, Aya A Mohamed, El-Chaimaa B. Mohamed, Shaker A. Mousa, Mostafa H. Elberry, Hossam Taha Mohamed |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
NS3
Organic Chemistry Biophysics Pharmaceutical Science Bioengineering 02 engineering and technology General Medicine 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Molecular biology 0104 chemical sciences Biomaterials Chitosan chemistry.chemical_compound chemistry Apoptosis Drug Discovery Curcumin MTT assay 0210 nano-technology NS5A Cytotoxicity IC50 |
| Zdroj: | International Journal of Nanomedicine. 15:2699-2715 |
| ISSN: | 1178-2013 |
| Popis: | Purpose Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7. Methods Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot. Results The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8 µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibition of viral entry and replication, which was confirmed with HCV core protein expression. Conclusion CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|