Highly efficient conotoxin delivery enabled by a bio-derived ionic liquid

Abstract

Drug delivery remains a challenge in the field of medicine. Current administration methods limit the application of peptide-protein drugs. The non-injectable administration of polypeptide and protein drugs has frequently been a key research topic in the field of drug delivery. Conotoxins (CTX) are one class of these polypeptides, which shows excellent biological efficacy. However, CTX also has drawbacks because of its hydrophilicity and polarity, which restricts its application to invasive drug delivery such as injections and significantly limits its clinical application. In this study, we developed an efficient and practical transdermal delivery system using an ionic liquid based on matrine and coconut oleic acid. In vitro penetration experiments demonstrated that the developed system could effectively deliver CTX to the dermis of the skin, with the cumulative absorption in the skin increased by 4.87 times. Moreover, the synergistic merits of ionic liquids and CTX contribute to the excellent antioxidant, antibacterial, and moisturizing effects at the cellular level. In addition, high safety was confirmed in animal experiments. In particular, the combined system exhibited outstanding efficacy for the improvement of skin elasticity and inhibiting wrinkle formation in population clinical tests. Therefore, this study expands the application of matrine-based ionic liquids in drug delivery and provides a novel methodology that promotes the efficiency of non-invasive drug delivery.