Liposome-mediated oral drug delivery in adult <i>Drosophila</i>

Abstract Drosophila melanogaster is a highly useful model for genetic analysis of disease phenotypes with over 60% of human disease-causing genes represented within the fly genome. However, the use of Drosophila for identifying and testing potential disease therapeutics is limited by several confounding effects on drug efficacy, including reduced ingestion owing to drug unpalatability or limited uptake from the intestine, particularly in adult flies. We propose here that liposome-mediated drug delivery can overcome these limitations. We demonstrate using fluorescently labelled liposomes that adult flies will readily consume liposomes which then effectively cross the intestinal epithelium to distribute their cargo to peripheral tissues, including the fat body, flight muscle, ovary and brain. We show that liposome encapsulation can mask the unpalatable taste of the insecticide, paraquat, thereby increasing its ingestion. Moreover, while ingestion of naked paraquat causes significant cellular damage to the intestinal epithelium, paraquat encapsulation within liposomes limits these effects. Lastly, we show that liposome encapsulation of the mitogen-activated protein kinase kinase (MEK) inhibitor, trametinib, maintains its bioactivity to produce systemic effects. Together, these results show that liposome encapsulation of compounds is an effective means for oral drug delivery in Drosophila with the potential to enhance ingestion and systemic distribution.