Silkworm (Bombyx mori) as a Promising Invertebrate Model for Drug Discovery, Pharmacokinetic Evaluation, and Preclinical Screening: Current Insights and Future Prospects

Abstract

The silkworm (Bombyx mori) has emerged as a promising invertebrate model for biomedical research, providing an ethical, cost-effective, and practical alternative to vertebrate systems for preliminary drug screening and pharmacokinetic studies. Its conserved metabolic pathways, similarity in drug disposition processes, and cytochrome P450-mediated reactions ensure translational relevance to mammalian systems. The availability of a fully sequenced genome and advanced molecular tools such as CRISPR/Cas9 and RNAi further enhances its potential for developing disease-specific and humanized models. Bombyx mori has been successfully employed beyond antimicrobial and antidiabetic drug screening to model complex metabolic disorders, including hyperuricemia, phenylketonuria, and kidney stone formation, underscoring its versatility in pathophysiological studies. Integration with high-throughput systems and modern technologies such as artificial intelligence and omics approaches offers significant opportunities to accelerate drug discovery and improve predictive accuracy for human pharmacology. Despite its potential, several limitations persist, such as the lack of adaptive immunity, variations in phase II metabolic conjugation, and anatomical differences that hinder direct translation of pharmacokinetic data. Overcoming these challenges through genetic modification, improved rearing techniques, and standardized experimental protocols will be crucial for wider implementation. Overall, Bombyx mori offers a scientifically sound, ethically responsible, and sustainable model that can significantly decrease dependence on mammalian systems while improving the efficiency of preclinical research.