In vitro and in vivo correlation of injectable lipid-based nanomedicines: From dissolution to protein coronas

Lipid-based nanomedicines (LBNMs) represent a transformative frontier in improving drug bioavailability and achieving spatiotemporally precise delivery of therapeutic agents. However, establishing robust in vitro-in vivo correlation (IVIVC) for LBNMs remains a significant challenge due to the complexity of their interactions with biological systems after administration. Conventional IVIVC approaches, often relying on simplistic in vitro dissolution models, frequently fail to recapitulate dynamic physiological processes, leading to discrepancies between predicted and actual in vivo performance. Recent advancements in understanding protein coronas-mediated phenomena have revolutionized nanomedicines research by unraveling how adsorbed biomolecules at the nanoparticle interface dictate physiological processes such as immune system interplay and biodistribution. This review systematically evaluates the state-of-the-art models for IVIVC of LBNMs and the emerging roles of protein coronas in bridging the gap between in vitro characterization and in vivo behavior, emphasizing the necessity of integrating protein coronas analysis into IVIVC frameworks. • Conventional dissolution-focused IVIVC models fail to predict in vivo behavior of injectable complex LBNMs. • Protein coronas dynamically reshape LBNM' biological identity and biodistribution, bridging IVIVC gaps of LBNMs.