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

Abstract

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 °C, 25 °C and 4 °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.