Enhancing drug administration in Drosophila melanogaster: a method for using solid dispersions for improved solubility and bioavailability.

Abstract

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.