title: Inhibition of influenza A virus infection in vitro by saliphenylhalamide-loaded porous silicon nanoparticles.
abstract: Influenza A viruses (IAVs) cause recurrent epidemics in humans, with serious threat of lethal worldwide pandemics. The occurrence of antiviral-resistant virus strains and the emergence of highly pathogenic influenza viruses have triggered an urgent need to develop new anti-IAV treatments. One compound found to inhibit IAV, and other virus infections, is saliphenylhalamide (SaliPhe). SaliPhe targets host vacuolar-ATPase and inhibits acidification of endosomes, a process needed for productive virus infection. The major obstacle for the further development of SaliPhe as antiviral drug has been its poor solubility. Here, we investigated the possibility to increase SaliPhe solubility by loading the compound in thermally hydrocarbonized porous silicon (THCPSi) nanoparticles. SaliPhe-loaded nanoparticles were further investigated for the ability to inhibit influenza A infection in human retinal pigment epithelium and Madin-Darby canine kidney cells, and we show that upon release from THCPSi, SaliPhe inhibited IAV infection in vitro and reduced the amount of progeny virus in IAV-infected cells. Overall, the PSi-based nanosystem exhibited increased dissolution of the investigated anti-IAV drug SaliPhe and displayed excellent in vitro stability, low cytotoxicity, and remarkable reduction of viral load in the absence of organic solvents. This proof-of-principle study indicates that PSi nanoparticles could be used for efficient delivery of antivirals to infected cells.
authors.affiliation: Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Finland.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Bimbo
authors.forename: Oxana V
authors.initials: OV
authors.lastname: Denisova
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.forename: Martti
authors.initials: M
authors.lastname: Kaasalainen
authors.forename: Jef K
authors.initials: JK
authors.lastname: De Brabander
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.forename: Laura
authors.initials: L
authors.lastname: Kakkola
authors.forename: Denis
authors.initials: D
authors.lastname: Kainov
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D004285:Dogs; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy*; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D012459:Salicylates / Q000008:administration & dosage*; D012825:Silicon / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D000577:Amides; D004337:Drug Carriers; D012459:Salicylates; D012997:Solvents; C574373:saliphenylhalamide; D012825:Silicon