title: Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles.
abstract: A new nanoparticulate system for foscarnet delivery was prepared and evaluated. Nanoparticles were obtained by ionotropic gelation of chitosan induced by foscarnet itself, acting as an ionotropic agent in a manner similar to tripolyphosphate anion. A Doehlert design allowed finding the suitable experimental conditions. Nanoparticles were between 200 and 300nm in diameter (around 450nm after redispersion). Nanoparticle size increased after 5h, but no size increase was observed after 48h when nanoparticles were crosslinked with glutaraldehyde. Zeta potential values of noncrosslinked and crosslinked nanoparticles were between 20 and 25mV, while drug loading of noncrosslinked nanoparticles was about 40% w/w (55% w/w for crosslinked nanoparticles). Nanoparticle yield was around 25% w/w. Crosslinked nanoparticles showed a controlled drug release. Foscarnet released from nanoparticles maintained the antiviral activity of the free drug when tested in vitro against lung fibroblasts (HELF) cells infected with HCMV strain AD-169. Moreover, nanoparticles showed no toxicity on non-infected HELF cells. These nanoparticles may represent a delivery system that could improve the therapeutic effect of foscarnet.
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy. Electronic address: russo@difar.unige.it.
authors.forename: E
authors.initials: E
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Gaglianone
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Baldassari
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Parodi
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cafaggi
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Zibana
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Ospedale San Luigi Gonzaga Regione Gonzole 10, 10043 Orbassano, TO, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Donalisio
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Ospedale San Luigi Gonzaga Regione Gonzole 10, 10043 Orbassano, TO, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Ospedale San Luigi Gonzaga Regione Gonzole 10, 10043 Orbassano, TO, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Lembo
authors.affiliation: Department of Pharmacy, University of Genova, Viale Cembrano 4, 16148 Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Caviglioli
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects; D004355:Drug Stability; D004705:Endocytosis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D005453:Fluorescence; D017245:Foscarnet / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005976:Glutaral / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000196:embryology; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D049452:Green Fluorescent Proteins; D017245:Foscarnet; D048271:Chitosan; D005976:Glutaral
keywords: Antiviral activity; Controlled release; Foscarnet; Ionotropic gelation; Nanoparticles; Stability