Development of an aciclovir implant for the effective long-term control of herpes simplex virus type-1 infection in Vero cells and in experimentally infected SKH-1 mice.
Human herpes simplex virus type-1 (HSV-1) is treatable with oral doses of an antiviral agent such as aciclovir (ACV), a drug that has poor bioavailability. An alternative for delivering ACV would employ a long-lived subcutaneous implant that would allow for near zero-order drug delivery kinetics. This study aimed to develop an implant composed of a matrix of silicone and ACV that is capable of sustained long-term release of ACV. Once the implants had been created, release of ACV from the implants was determined and quantified in vitro using a spectrophotometric assay for the drug. Solvent-exposed surface area of the implant (2.86 mm(2), 6.28 mm(2), 34.62 mm(2) and 100.48 mm(2)) had a significant effect on release kinetics, whereas temperature (37 degrees C, 25 degrees C and 4 degrees C) and pH (6.0, 7.0 and 8.0) did not. The implants were also used successfully to suppress HSV-1 (KOS)-induced cytopathic effect in cultured Vero cells. The implants protected HSV-1-infected SKH-1 mice from viral reactivation (n = 37; P = 0.0367) via ultraviolet light compared with mice that were untreated (n = 37). Furthermore, mice that received silicone-only implants had no lowered risk of reactivation (n = 34; P = 0.7268), demonstrating the antiviral efficacy of the ACV implants.
Johnson
Tory P
TP
Towson University Herpes Virus Lab, Department of Biological Sciences, Towson University, 8000 York Road, Towson, MD 21252, USA.
Frey
Robin
R
Modugno
Melissa
M
Brennan
Timothy P
TP
Margulies
Barry J
BJ
D000212:Acyclovir / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002522:Chlorocebus aethiops; D003692:Delayed-Action Preparations / Q000494:pharmacology / Q000627:therapeutic use*; D004343:Drug Implants; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects; D051379:Mice; D014709:Vero Cells; D014775:Virus Activation / Q000187:drug effects
D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D000212:Acyclovir