Abstract
Treatment for herpes simplex virus-1 and -2 (HSV-1 and -2) patients who suffer from recurrent outbreaks consists of multiple daily doses of the antiviral drugs acyclovir (ACV), penciclovir, or their more orally bioavailable derivatives valacyclovir or famciclovir. Drug troughs caused by missed doses may result in viral replication, which can generate drug-resistant mutants along with clinical sequelae. We developed a molecularly homogeneous mixture of ACV with the bioerodable polymer polycaprolactone. Through scanning electron microscopy, infrared spectroscopy, gel permeation chromatography, 1H NMR, and differential scanning calorimetry, our method of combining drug and polymer, termed Volatile Acid-Solvent Evaporation (VASE), does not compromise the integrity of polymer or drug. Furthermore, VASE creates materials that deliver therapeutic amounts of drug consistently for approximately two months. Devices with high enough drug loads diminish primary infection of HSV-1 in Vero cells to the same level as seen with a single dose of ACV. Our data will lead to further experiments in animal models, demonstrating efficacy in preventing reactivation of these viruses with a single intervention, and with other antiviral drugs amenable to such manipulation. Additionally, this type of treatment would leave no trace after its useful lifetime, as drug is released and polymer matrix is degraded in vivo.
Highlights
The human herpes simplex virus type-1 (HSV-1) is an alphaherpesvirus in the genus Simplexvirus [1]
It is estimated that 80% of the adult population carries HSV-1, typically asymptomatically, with primary oral infection usually occurring during childhood [1, 3]
Reactivation of oral herpes occurs in an average of 33% of those infected with HSV-1 [2]
Summary
The human herpes simplex virus type-1 (HSV-1) is an alphaherpesvirus in the genus Simplexvirus [1]. It is estimated that 80% of the adult population carries HSV-1, typically asymptomatically, with primary oral infection usually occurring during childhood [1, 3]. Many individuals never see emergence of disease from the latent stage of infection; others have recurrent outbreaks. Reactivation of oral herpes occurs in an average of 33% of those infected with HSV-1 [2]. Of those who do Journal of Drug Delivery see a recurrence, 5% have recrudescence rates of at least one episode per month, 34% have at least one episode every two to eleven months, and 61% have at least one episode per year [1, 6]. In immunocompromised individuals outbreaks can occur with increased frequency and are more difficult to control [7,8,9]
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