Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 121 | 2026
Research Articles

Nanoemulsions loaded with β-caryophyllene and resveratrol for herpes infections

Isabella Dai Prá1,2, Douglas Santos Porto1, Bianca Costa Bernardo Port1, Luíse Gauer Schulte1,2, Débora Fretes Argenta1, Thiago Caon1, Izabella Thaís Silva1,2,+

1Universidade Federal de Santa Catarina, Departamento de Ciências Farmacêuticas, Florianópolis, SC, Brasil
2Universidade Federal de Santa Catarina, Departamento de Microbiologia, Imunologia e Parasitologia, Florianopolis, SC, Brasil

DOI: 10.1590/0074-02760250333
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ABSTRACT

BACKGROUND 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.
OBJECTIVES 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.
METHODS 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.
FINDINGS 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.
MAIN CONCLUSIONS 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.

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Financial support: CAPES provided a master’s fellowship to IDP in the Programa de Pós-Graduação em Farmácia, UFSC.
+ Corresponding author: izabella.thais@ufsc.br | ORCID https://orcid.org/0000-0002-1893-4317
Received 14 November 2025
Accepted 15 July 2026

HOW TO CITE
Prá ID, Porto DS, Port BCB, Schulte LG, Argenta DF, Caon T, et al. Nanoemulsions loaded with ?-caryophyllene and resveratrol for herpes infections. Mem Inst Oswaldo Cruz. 2026; 121: e250333.
Handling editor: Geovane Dias-Lopes | ORCID https://orcid.org/0000-0003-4448-1398

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