Nanoemulsions loaded with ß-caryophyllene and resveratrol for herpes infections

Herpes Simplex Virus (HSV) infection represents a global health concern with a significant impact on affected individuals' quality of life. Conventional treatment relies on nucleoside analogues such as acyclovir, which, although effective, have limitations including viral resistance and low bioavailability. In this context, natural products such as resveratrol (RSV) and β-caryophyllene (BCP) emerge as promising alternatives due to their antiviral and immunomodulatory properties. However, these compounds present challenges related to stability and solubility, necessitating the use of controlled drug delivery systems such as nanoemulsions.

This study aimed to develop and characterise nanoemulsions containing RSV and BCP, either individually or in combination, for the treatment of HSV type 1 (HSV-1) infections.

The nanoemulsions were prepared using a low-energy spontaneous emulsification technique and characterised for particle size, polydispersity index (PDI), and zeta potential. The antiviral activity, cytotoxicity, and wound-healing potential of the nanoemulsions were evaluated in vitro using VERO and human gingival fibroblast (HGF) cells.

Results showed that RSV exhibited significant antiviral activity against HSV-1, while BCP demonstrated moderate activity. Nanoencapsulation improved the biocompatibility of RSV but increased the cytotoxicity of BCP. The combination of RSV and BCP in nanoemulsions showed enhanced antiviral activity, with inhibition percentages above 70%. However, the nanoemulsions did not significantly promote wound healing in HGF cells. Additionally, the nanoemulsions did not protect against Ultraviolet Crosslinker (UVC)-induced cell damage.

Nanoemulsions containing RSV and BCP demonstrated enhanced antiviral activity against HSV-1, particularly when combined, suggesting a synergistic effect between both compounds. Nanoencapsulation improved the biocompatibility of RSV but increased the cytotoxicity of BCP. Although no significant effects were observed in wound healing or UV protection assays, the results support nanoemulsions as a promising platform for improving the antiviral performance of these compounds for topical HSV-1 treatment.