International Journal of Nanomedicine (Apr 2020)
Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines
Abstract
Samah A Loutfy,1,2 Mostafa H Elberry,1 Khaled Yehia Farroh,3 Hossam Taha Mohamed,4,5 Aya A Mohamed,4 ElChaimaa B Mohamed,1 Ahmed Hassan Ibrahim Faraag,6 Shaker A Mousa7 1Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Nanotechnology Research Center, British University, Cairo, Egypt; 3Nanotechnology and Advanced Materials Central Lab, Agricultural Research Center, Giza, Egypt; 4Faculty of Biotechnology, October University for Modern Sciences and Arts, 6th October, Giza, Egypt; 5Department of Zoology, Faculty of Science,Cairo University, Giza, Egypt; 6Botany and Microbiology Department, Bioinformatics Center, Faculty of Science, Helwan University, Cairo, Egypt; 7The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USACorrespondence: Samah A LoutfyVirology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Kasr El Eini, Fom El-Khalig, Cairo 11796, EgyptTel +20 1222840964Email [email protected]: 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.Keywords: caspase-dependent pathway, chitosan curcumin nanocomposite, hepatitis C virus genotype 4a, Huh7, docking
