Volatile Acid-Solvent Evaporation (VASE): Molecularly Homogeneous Distribution of Acyclovir in a Bioerodable Polymer Matrix for Long-Term Treatment of Herpes Simplex Virus-1 Infections
Year: 2018
Type: article
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.
Source: Journal of Drug Delivery
DOI: 10.1155/2018/6161230
Authors: James R. Stegman, Jill K. Badin, Kaitlyn A. Biles, Thamar Etienne, Sogand Fartash-Naini, Ariel D. Gordon, Zachary W. Greeley, Benjamin W. Harding, Ricardo J. Mack, Danielle Masica, Ashley N. Nelson, Amandeep K. Samra, Sarah E. Smith, Gabrielle P. Thomas, Haley J. Zack, Timothy J. Brunker, Barry J. Margulies
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Funders: Johns Hopkins University, Towson University, National Institutes of Health, Directorate for Biological Sciences, Jess and Mildred Fisher College of Science and Mathematics, Graduate Student Association, Fordham University, National Institute of Allergy and Infectious Diseases, Division of Graduate Education
OpenAlex ID: W2892977836
