Gallic acid (GA) and ellagic acid (EA) are natural compounds known for their antioxidant properties and potential health benefits. In this study, a relevant approach was the incorporation of these substances into the gel with Poloxamer407®, a vehicle widely used in pharmaceutical formulations. These acids, due to their already known properties, are promising in terms of therapeutic potential, either alone or in combination, due to their complementary properties. Gallic acid has antioxidant, anti-inflammatory and antimicrobial properties, while ellagic acid shows anticancer, antiviral and photoprotective activity. Thus, the combination of these substances in the same vehicle was tested to take advantage of a probable complementary effect, aiming to provide additional therapeutic benefits.

Numerous studies have proven the antioxidant effects of gallic acid, which are related to the reduction of reactive oxygen species (ROS) production. Among the cellular organelles, mitochondria play a crucial role in the generation of ROS, and gallic acid directs its effects mainly to the specific signaling pathways and molecules of this organelle (Lin et al., 2020). Ellagic acid has attracted increasing interest due to its potential health benefits, such as its antioxidant, anti-inflammatory, antiviral and anticancer effects. Several studies have also demonstrated the effectiveness of ellagic acid against a variety of pathogens, including bacteria, fungi and parasites. In addition, ellagic acid may play a role in reducing UV radiation damage, either by mediating the inflammatory cascade or by reducing oxidative stress in skin cells (Bai et al., 2022). In this context, compounds with antioxidant properties, such as ellagic acid and gallic acid, have been the target of investigations as potential therapeutic agents, these compounds are known for their ability to neutralize ROS, reducing oxidative stress.

However, before using these compounds in therapeutic formulations, it is essential to assess their acute toxicity. Toxicity assessment is a key step in drug discovery, as only compounds that demonstrate safety in preclinical trials can progress to the clinical phases. Consequently, several preclinical toxicity models have been developed and used to predict the toxic behavior of new compounds in humans and preliminarily exclude unsafe compounds (Brai et al., 2023).

LD50 values (lethal dose 50, which is the dose of a substance expected to cause the death of 50% of the animals tested) or LC50 (lethal concentration 50, via inhalation) are often used in acute systemic toxicity tests in rodents to classify substances into different toxicity categories, which in turn determine the hazard warnings displayed on product labels (Strickland et al., 2018). However, the use of alternative models, such as invertebrates, is increasingly gaining recognition as a valid approach to assess substance toxicity, providing an ethical alternative and reducing the need for vertebrate animal testing.

The incorporation of ellagic acid and gallic acid into the gel with Poloxamer407® allows for a precise and controlled administration, simulating topical application on skin wounds. In addition to the evaluation of acute toxicity, the potential antioxidant effect of these compounds on Zophobas morio larvae will also be evaluated. Biochemical parameters related to oxidative stress will be analyzed, such as the activity of antioxidant enzymes and the concentration of reactive oxygen species. The results of this study will provide valuable information on the acute toxicity of ellagic acid and gallic acid and their potential antioxidant effect on Zophobas morio larvae. These data will contribute to the future development of therapies aimed at reducing oxidative stress and promoting wound healing.

Thus, the objective of this study was to develop topical gels containing gallic acid, ellagic acid and their combination, evaluate these gels for drug release capacity, as well as evaluate them for acute toxicity and biomarkers of oxidative stress, and support their applicability for the development of topical therapies for skin conditions.