Obisesan, OSTshweu, Lesego LNkabinde-Thete, LindiweRamalapa, Bathabile , OS TshweuNgoepe, MPSaartjie, RMufhandu, HT2025-07-222025-07-222025-061748-60411748-605Xhttp://hdl.handle.net/10204/14304Herpes simplex virus type 2 (HSV-2) remains a significant public health concern due to its high rates of mortality and morbidity. While various chemotherapeutic options exist for treating HSV-2, they are often inadequate as none provide a definitive cure, and there is a growing issue of drug-resistant strains. The introduction of nanomedicine for antiviral drug delivery offers a promising avenue to enhance the effectiveness of these treatments. This study explored an innovative approach to treating HSV-2 by encapsulating valacyclovir in biodegradable polycaprolactone (PCL) using a double emulsion technique. The formulated valacyclovir-loaded polymeric nanoparticles were characterized, revealing monodispersed particles with an average hydrodynamic size ranging from 154.9 ± 2.1 to 232.8 ± 6.2 nm, along with an encapsulation efficiency of 50%–66% and a drug loading capacity of 11.6%–13.9%. Additionally, there is no significant cytotoxicity of the test compounds to Vero cells at 0.3 mg ml−1 concentration with a cell viability within the range of 85 ± 13.6%−100 ± 4.8%. The antiviral activity of both the free drug (valacyclovir) and the valacyclovir-loaded polymeric nanoparticles was assessed in HSV-2 infected Vero cells. The results demonstrated that the valacyclovir-loaded nanoparticles exhibited a 1.2–1.3fold (p < 0.005) increase in antiviral efficacy compared to the free drug. This study thus presents a novel nanotechnology-based treatment approach for HSV-2, offering enhanced antiviral effectiveness over traditional treatments.FulltextenHerpes simplex virus type 2HSV-2NanomedicineSynthesis, characterization and antiviral efficacy of valacyclovir loaded polymeric nanoparticles against wild-type herpes simplex virus type 2Articlen/a