title: Ethosomes for the delivery of anti-HSV-1 molecules: preparation, characterization and in vitro activity.
abstract: This paper describes the production, characterization and in vitro activity of ethosomes containing two molecules with antiviral activity, such as acyclovir (ACY) and N1-beta-D-ribofuranosyl-pyrazole [3,4d]pyridazin-7(6p-chlorine-phenyl)-one nucleoside (N1CP). Ethosomes were prepared and morphologically characterized by Cryo-TEM. The encapsulation efficiency was 92.3 +/- 2.5% for ACY and 94.2 +/- 2.8% for N1CP. The release of the drug from vesicles, determined by a Franz cell method, indicated that both drugs were released in a controlled manner. In order to possibly guarantee the stability during long-term storage ethosome suspensions was freeze-dried. It was found that the freeze-dried ethosomes' cakes were compact, glassy characterized by low density and quick re-hydration. However, the storage time slightly influences the percentage of drug encapsulation within ethosomes showing a drug leakage after re-hydration around 10%. The antiviral activity against HSV-1 of both drugs was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that ethosomes allowed a reduction of the ED50 of N1CP evidencing an increase of its antiviral activity. However, ACY remains more active than N1CP. No differences are appreciable between drug-containing ethosomes before and after freeze-drying. Taken together these results, ethosomal formulation could be possibly proposed as mean for topical administration of anti-herpetic molecules.
authors.affiliation: Department of Pharmaceutical Sciences, University of Ferrara BioPharmaNet, Technologic Pole of Ferrara University, Ferrara, Italy. crt@unife.it
authors.forename: R
authors.initials: R
authors.lastname: Cortesi
authors.forename: L
authors.initials: L
authors.lastname: Ravani
authors.forename: A N
authors.initials: AN
authors.lastname: Zaid
authors.forename: E
authors.initials: E
authors.lastname: Menegatti
authors.forename: R
authors.initials: R
authors.lastname: Romagnoli
authors.forename: M
authors.initials: M
authors.lastname: Drechsler
authors.forename: E
authors.initials: E
authors.lastname: Esposito
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000737:chemistry; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004058:Diffusion; D004339:Drug Compounding; D004563:Electrochemistry; D005612:Freeze Drying; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D008855:Microscopy, Electron, Scanning; D008861:Microsomes; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D013778:Tetrazolium Salts; D013844:Thiazoles; D010948:Viral Plaque Assay
chemical_list: D000998:Antiviral Agents; D014677:Pharmaceutical Vehicles; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D000212:Acyclovir