Mechanistic insights into the biological effects of environmentally relevant pharmaceutical-loaded real-life polypropylene microplastics in Drosophila melanogaster.

Although the adsorption of pharmaceuticals by microplastics (MPLs) may reduce environmental contaminant concentrations, their effects on bioavailability and biological toxicity following ingestion remain poorly studied. To mimic environmentally relevant exposure, environmentally relevant polypropylene microplastics (PP-MPLs) derived from post-consumer plastic products (real-life) were used as carriers for the pharmaceuticals paracetamol (PCM) and ciprofloxacin (CFX), using Drosophila larvae in vivo model. Free PCM and CFX were tested at concentrations equivalent to their respective adsorption loadings on PP-MPLs (0.03% and 0.02% w/w, respectively), enabling direct comparison under environmentally realistic conditions. PP-MPLs, with or without adsorbed pharmaceuticals, retained their irregular morphology and heterogeneous size distribution, representing an environmentally relevant mixture of micro- and nanoscale particles. Following oral exposure, PP-MPLs, either alone or carrying adsorbed pharmaceuticals, sequentially traversed the intestinal barrier penetrating the peritrophic membrane, accumulating within enterocytes, and ultimately reaching hemolymph. Particle exposure induced extensive enterocyte vacuolation, significantly increased intracellular reactive oxygen species (ROS), and triggered targeted gene-expression changes involving antioxidant, immune, detoxification, and stress-response pathways, while genes associated with digestive function were consistently deregulated. Despite elevated oxidative stress, PP-MPLs did not alter mitochondrial membrane potential. In contrast, free PCM induced significant mitochondrial depolarization without increasing ROS, whereas this effect was abolished following adsorption onto PP-MPLs, potentially due to reduced bioavailability. Moreover, pharmaceutical-loaded PP-MPLs did not elicit additive molecular toxicity compared with PP-MPLs alone.