Cheku Sunayn, Rokusek Blase, Pattabiraman Mahesh, Carlson Kimberly A
Department of Biology, University of Nebraska at Kearney, Kearney, NE, USA.
Department of Chemistry, University of Nebraska at Kearney, Kearney, NE, USA.
Fly (Austin). 2025 Dec;19(1):2497565. doi: 10.1080/19336934.2025.2497565. Epub 2025 Apr 25.
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 . The solid dispersions were validated, , 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 using subcutaneous injections, CAFE assay, or by mixing it with solid food.
是用于帕金森病、阿尔茨海默病、肥胖症和糖尿病等疾病研究的广泛使用的模式生物。然而，基于化合物给药的果蝇毒理学和行为学研究一直受到与疏水性化合物给药效率低下相关的技术难题的阻碍。本研究阐述了一种制备和分配基于聚乙二醇8000（PEG 8000）的固体分散体的通用方法，该固体分散体包含三种疏水性化合物，即二硬脂酰甘油（DSG）、格尔德霉素（GA）和米非司酮（RU486）。使用核磁共振光谱（NMR）对固体分散体进行验证，结果表明其具有更高的水溶性。该研究还描述了三种不同的固体分散体给药方法：皮下注射、混入固体食物以及毛细管取食试验（CAFE）。我们发现1%二甲亚砜（DMSO）的存在会降低果蝇存活率，而聚乙二醇（PEG）没有不良影响。最后，我们表明，与溶解在乙醇中的RU486相比，制备的PEG - RU486制剂显示出生物利用度提高的迹象。该研究中描述的方法提供了一种简单有效的手段，可通过皮下注射、CAFE试验或将其与固体食物混合的方式将疏水性化合物给予果蝇。
