title: Increased efficacy of acyclovir-loaded microparticles against herpes simplex virus type 1 in cell culture.
abstract: Acyclovir is one of the most effective and selective agents against viruses of the herpes group. In order to increase its antiviral activity, acyclovir loaded microparticles, prepared by an O/W solvent evaporation method were developed. Their antiviral activity against herpes simplex virus type 1 (HSV-1) and toxicity were evaluated on Vero cells and then compared with those presented by a drug solution. The 50% inhibitory concentration (IC(50)) values for acyclovir loaded microspheres determined by plaque reduction assays at 48 and 96 h, were found to be 1.06 +/- 0.01 microM and 0.15 +/- 0.03 microM, respectively, while the equivalent values obtained for an acyclovir solution were 1.28 +/- 0.04 microM at 48 h and 0.27 +/- 0.02 microM at 96 h. These results indicate that acyclovir shows a higher antiviral activity, against herpes simplex virus type 1, when this drug was loaded in microparticles rather than as a drug solution, especially after 96 h of incubation. The toxicity of these microparticles was determined by the MTT test at 48 and 96 h. At 48 h only a small toxicity was found (cell viability ranged from 72 to 82%, with the higher concentration tested) and it could not be attributed to the microparticles, since the acyclovir control solution showed similar toxicity values. However, after 96 h a higher toxicity was observed with acyclovir microparticles as well as with the unloaded ones (cell viability located between 60 and 70%). In summary, acyclovir-loaded microparticles have shown to be promising carriers for the effective delivery of acyclovir in the treatment of HSV-1 infections in cells so they can have a potential use in vivo.
authors.affiliation: Departamento de Farmacia y TecnologIa Farmacéutica, Universidad de Navarra, Pamplona, Spain.
authors.forename: E Ga
authors.initials: EG
authors.lastname: de Jalón
authors.forename: M J
authors.initials: MJ
authors.lastname: Blanco-Príeto
authors.forename: P
authors.initials: P
authors.lastname: Ygartua
authors.forename: S
authors.initials: S
authors.lastname: Santoyo
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage*; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D008863:Microspheres; D014709:Vero Cells
chemical_list: D000212:Acyclovir