Unlocking the brain: Biodistribution insights into tween 80 nanoliposomes in healthy brains

Limited drug penetration across the blood-brain barrier hinders brain tumor therapy. This study evaluated doxorubicin-loaded nanoliposomes with varying Tween 80 contents, investigating formulation characteristics, release profiles, cytotoxicity on cancer and healthy cells, and tissue distribution in healthy models. Nanoliposomes were prepared via thin-film hydration. Physicochemical properties, in vitro drug release at physiological and acidic pH, and cytotoxicity (MTT assay and IC₅₀) on C6 cells and normal NIH 3 T3 cells (including empty-carrier biosafety) were assessed. In vivo tissue distribution and histopathological safety were also examined in mice. Formulations showed composition-dependent size and 3-month stability. Formulation F2 emerged as the lead candidate, exhibiting optimal size (142.4 nm), PDI (0.139), encapsulation efficiency (82.4%), and pH-responsive release (80-90% at pH 5.5 vs. <10% at pH 7.4). F2 maintained potent cytotoxicity on C6 cells (IC₅₀: 0.44 μg/mL) while demonstrating high biosafety on normal NIH 3 T3 cells, showing >90% viability with empty blanks and a markedly higher IC₅₀ (20.67 μg/mL) than free DOX. In vivo, F2 achieved superior brain accumulation at 24 and 48 h (2.61 and 2.78 μg/g; p < 0.05 vs. DOX) while reducing cardiac uptake (2.29 vs. 14.49 μg/g at 24 h). Formulation F2 balances colloidal stability, reduced cardiotoxicity, and superior brain accumulation, supporting its potential for neuro-oncology applications.