The Pharmaceutical Exposome: Micro- and Nanoplastic Leaching From Primary Packaging and Its Toxicological Impact on the Human Gut Microbiota

The pharmaceutical exposome encompasses human exposure to non-biological contaminants associated with medicinal products, including microplastics (MPs) and nanoplastics (NPs) potentially released from primary packaging. Materials such as high-density polyethylene, polyvinyl chloride, and polyethylene terephthalate may contribute particles during storage, transport, and handling, particularly in liquid formulations. Experimental and preclinical studies suggest that MPs/NPs can alter gut microbiota composition, reduce beneficial bacterial populations, impair short-chain fatty acid production, and promote inflammatory responses. Reported cellular effects include oxidative stress, mitochondrial dysfunction, disruption of intestinal tight junctions, and lysosomal damage. MPs/NPs may also provide surfaces for biofilm formation and interact with active pharmaceutical ingredients through proposed “Trojan Horse” mechanisms, although the pharmaceutical relevance of these processes remains uncertain. Chemical constituents associated with packaging, including phthalates and residual catalysts, may provide additional exposure pathways with potential inflammatory or endocrine-disrupting effects. Pediatric patients, individuals receiving long-term medications, and patients with pre-existing gastrointestinal dysbiosis may warrant particular attention because of potential biological susceptibility or repeated exposure. Analytical characterization remains challenging because pharmaceutical matrices are complex and highly susceptible to contamination, requiring complementary spectroscopic and mass-spectrometric approaches with rigorous quality control. Importantly, direct human evidence specifically linking pharmaceutical packaging-derived MPs/NPs to clinically relevant exposure or adverse health outcomes remains sparse. Current evidence should therefore be interpreted cautiously, with greater emphasis on source-specific human exposure assessment, standardized analytical methods, longitudinal studies, evidence-based risk evaluation, and harmonized regulatory frameworks.