Dosimetry of Inhaled Aerosols: From Exposure to Target Tissue Dose in Risk Assessment and Drug Delivery

Inhaled aerosol dosimetry is a critical discipline bridging exposure to biological effect in both therapeutic and toxicological contexts. This review integrates current knowledge on the physicochemical determinants of aerosol behavior such as particle size, solubility, surface charge, and hygroscopicity and their influence on deposition, translocation, and target tissue dose. We examine key deposition mechanisms across respiratory regions and evaluate established computational models, including multiple path particle dosimetry (MPPD), computational fluid dynamics (CFD), and physiologically based pharmacokinetic (PBPK) models, highlighting their strengths, limitations, and regulatory applications. Advanced experimental systems such as air-liquid interface (ALI) cultures, lung-on-chip platforms, and imaging-based techniques are discussed for their role in quantifying biologically effective doses. The review also addresses challenges in dose-response assessment, emphasizing the need for biologically relevant metrics like particle number and surface area over traditional mass concentration. Emerging applications of artificial intelligence and machine learning are explored for enhancing predictive accuracy and personalizing dosimetry. Finally, we identify future priorities, including standardization of dose metrics, integration of therapeutic and toxicological frameworks, and development of human-relevant, animal-free models. By aligning insights from pharmacology, toxicology, and computational science, this work advocates for a unified, translational approach to inhaled aerosol dosimetry to improve both drug delivery and public health protection.