| Summary: | Khaled AbouAitah,1,2 Anna Swiderska-Sroda,1 Ahmed Kandeil,3 Asmaa MM Salman4,†, Jacek Wojnarowicz,1 Mohamed A Ali,3 Agnieszka Opalinska,1 Stanislaw Gierlotka,1 Tomasz Ciach,5 Witold Lojkowski1 1Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland; 2Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), P.C.12622, Dokki, Giza, Egypt; 3Center of Scientific Excellence for Influenza Viruses, Water Pollution Research Department, Environmental Research Division, National Research Centre (NRC) P.C.12622, Dokki, Giza, Egypt; 4Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), P.C. 12622, Dokki, Giza, Egypt; 5Biomedical Engineering Laboratory, Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland†AMM Salman passed away on June 3, 2019Correspondence: Khaled AbouAitah; Witold Lojkowski Email k.abouaitah@labnano.pl; w.lojkowski@labnano.plBackground: Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses.Materials and Methods: In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model.Results: Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1β) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model.Conclusion: Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.Keywords: virucidal action, influenza H5N1 virus, immunomodulatory and anti-inflammatory, nanoformulations-drug delivery system, shikimic acid and quercetin natural prodrugs, mesoporous silica nanoparticles
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