Exploring Galleria mellonella as a Novel Model for Evaluating Permeation and Toxicity of Natural Compounds

Introduction Recent legislative advancements emphasize the need for alternative methods in assessing efficacy and safety while adhering to the 3Rs principles (reduce, replace, and refine) of animal experimentation. In this context, Galleria mellonella has become a well-established model in safety and efficacy research. However, existing studies predominantly focus on its use in injectable routes concerning pathogens and chemical compounds, leaving a significant gap in understanding other administration pathways, particularly topical application. To address this gap and contribute to the validation of G. mellonella as a model for cutaneous absorption studies, our investigation compares the toxicity data of gallic acid (GA) in mammalian models, alternative animal models such as G. mellonella and Caenorhabditis elegans, as well as monolayer cell cultures, providing insights valuable for future research. Methods This was an experimental study aimed at evaluating the toxicity and permeation of gallic acid (GA) using different in vivo and in vitro alternative models, including G. mellonella, C. elegans, and monolayer cell cultures. Our study specifically evaluated the toxicity of GA in solution using human keratinocytes (HaCat), human dermal fibroblasts (HDFa), and human liver cell lines (HepG2), in addition to invertebrate animal models of C. elegans and semi-solid formulations in G. mellonella via topical administration. The results demonstrated GA’s higher toxicity in C. elegans, followed by sequential susceptibility in HaCat, HepG2, and HDFa cells. Results Surprisingly, G. mellonella displayed a notably high tolerance to GA, presenting no discernible alterations in cellular immune responses in injectable nor topical administration. Observations of the humoral immune response in G. mellonella larvae showcased melanization both administration conditions, indicating absorption following topical administration of higher GA concentrations. Conclusions GA demonstrated low toxicity in cellular models, whereas G. mellonella revealed promise as a methodology for topical toxicity testing in cutaneous absorption. However, further research is essential to validate its efficacy. These findings demonstrated the potential to establish correlations in toxicology data between various alternative methodologies and mammals, potentially aiding in the prediction of toxicity in humans.