# Nanoparticles Loaded with Lippia graveolens Essential Oil as a Topical Delivery System: In Vitro Antiherpetic Activity and Biophysical Parameters Evaluation

## TL;DR

This study explores using nanoparticles loaded with Lippia graveolens essential oil to improve its antiviral effects against herpes simplex virus type 1 while preserving skin health.

## Contribution

The study introduces a nanoparticle-based delivery system that enhances the antiviral efficacy and reduces the cytotoxicity of Lippia graveolens essential oil.

## Key findings

- Nanoparticles loaded with essential oil showed 1.85-fold higher antiviral activity against HSV-1 compared to free essential oil.
- The nanoformulation improved skin hydration without affecting pH or transepidermal water loss.
- Nanoformulations exhibited favorable physicochemical properties for skin delivery, including a particle size of ~200 nm and low polydispersity.

## Abstract

Background/Objectives: The skin is a protective barrier against pathogens such as herpes simplex virus type 1 (HSV-1), which causes recurrent and highly prevalent skin infections worldwide. The increasing resistance of HSV-1 to conventional treatments has driven the search for new therapeutic alternatives. In this context, the essential oil of Lippia graveolens (EOL) has demonstrated promising antiviral activity; however, its high volatility limits direct skin application. To overcome this, polymeric nanoparticles (NPs) loaded with EOL were developed to improve its availability and antiviral efficacy. Methods: Nanoformulations were prepared by nanoprecipitation, and their antiviral activity against HSV-1 was evaluated using the plaque reduction assay. The effect of the nanoformulations on skin barrier integrity was assessed using an ex vivo porcine skin model and non-invasive techniques. Results: The NP-EOL exhibited physicochemical properties favorable for skin deposition, including a particle size around 200 nm, a polydispersity index of ≤ 0.2, and negative zeta potential. Moreover, NP-EOL showed 1.85-fold higher antiviral activity against HSV-1 compared with free EOL, while also reducing cytotoxicity in Vero cells. Conclusions: Results demonstrated that the NPs promoted skin hydration without altering pH or transepidermal water loss, suggesting they do not disrupt skin homeostasis. This study supports the potential of NP-based systems as effective topical delivery vehicles for EOL, representing a promising therapeutic alternative against HSV-1 skin infections.