This review traces the journey of nanosomes from administration until elimination, and discusses various biological barriers. The nanosomes are imported into the body through different routes and are localized into specified organ, cell, subcellular locations or organelle compartment. The nanosomes delivery to a specific destination depends on the surface chemistry, size, shape and the presence of specific ligands. Endocytosis/exocytosis cycles are involved in the import and export of the nanosomes. The mononuclear phagocytic system and ATP-binding cassette are universal checkpoints for nanosomes trafficking. The gastrointestinal milieu is the checkpoints for orally administered nanosomes. The mucociliary escalator is a specialized obstacle for inhaled nanosomes. Dermally applied nanosomes are tackled by Langerhans cells and keratinocytes. The nanosomes intended for subcellular destinations are mainly intercepted by lysosomes. Thus, nanosomes intended for biological administration must be designed to escape various barriers. The nanosomes affect cells function by alteration of redox status, and calcium signalling, ultimately, they are exocytosed from the cells.
Keywords: Drug delivery; barriers; endocytosis; exocytosis; nanosomes.