Sunayn Cheku, Blase Rokusek, Mahesh Pattabiraman, Kimberly A Carlson
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Enhancing drug administration in Drosophila melanogaster: a method for using solid dispersions for improved solubility and bioavailability.
Drosophila melanogaster is a widely used model organism for diseases such as Parkinson's disease, Alzheimer's disease, obesity, and diabetes. However, compound administration-based toxicological and behavioural studies on Drosophila have been hindered by technical difficulties associated with inefficient administration of hydrophobic compounds. This study illustrates a general method to make and distribute PEG 8000-based solid dispersions for three hydrophobic compounds, distearoylglycerol (DSG) geldanamycin (GA) and RU486 to D. melanogaster. The solid dispersions were validated, in vitro, using nuclear magnetic resonance spectroscopy (NMR), to have a higher aqueous solubility. The study also describes three different methods to administer the solid dispersions: subcutaneous injections, mixing in solid food, and the capillary feeder assay (CAFE). We show that the presence of 1% DMSO decreases survival, whereas PEG does not have an adverse effect. Lastly, we showed that the prepared PEG-RU486 formulation showed signs of enhanced bioavailability when compared to RU486 dissolved in ethanol. The methodology described in the study provides an easy and effective means to administer hydrophobic compounds to D. melanogaster using subcutaneous injections, CAFE assay, or by mixing it with solid food.
期刊介绍:
Fly is the first international peer-reviewed journal to focus on Drosophila research. Fly covers a broad range of biological sub-disciplines, ranging from developmental biology and organogenesis to sensory neurobiology, circadian rhythm and learning and memory, to sex determination, evolutionary biology and speciation. We strive to become the “to go” resource for every researcher working with Drosophila by providing a forum where the specific interests of the Drosophila community can be discussed. With the advance of molecular technologies that enable researchers to manipulate genes and their functions in many other organisms, Fly is now also publishing papers that use other insect model systems used to investigate important biological questions.
Fly offers a variety of papers, including Original Research Articles, Methods and Technical Advances, Brief Communications, Reviews and Meeting Reports. In addition, Fly also features two unconventional types of contributions, Counterpoints and Extra View articles. Counterpoints are opinion pieces that critically discuss controversial papers questioning current paradigms, whether justified or not. Extra View articles, which generally are solicited by Fly editors, provide authors of important forthcoming papers published elsewhere an opportunity to expand on their original findings and discuss the broader impact of their discovery. Extra View authors are strongly encouraged to complement their published observations with additional data not included in the original paper or acquired subsequently.