Liposomal Nanocarriers in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Formulation Design, Targeting...

Non-alcoholic fatty liver disease (NAFLD) affects one-quarter of the global population. The disease may progress from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma. Unfortunately, lifestyle interventions and pharmacotherapies provide limited benefits to NAFLD patients. This systematic review which was conducted according to PRISMA 2020 guidelines, study selection, and data extraction, evaluated preclinical studies published between 1 January 2021 and 4 April 2026 that investigated liposome-based nanocarriers for NAFLD/NASH. Out of 477 records identified, 19 studies met the eligibility criteria and were included in the review. The included studies demonstrated that liposomal formulations prepared using thin-film hydration exhibited characteristics such as particle sizes of 80-160 nm, low polydispersity, zeta potentials of -55 to +35 mV (depending on surface modification), encapsulation efficiencies exceeding 75%, and sustained biphasic release profiles. Mechanistically, these nanocarriers targeted pathways by suppressing de novo lipogenesis through inhibition of FASN and SREBP-1c, enhancement of fatty acid oxidation through activation of AMPK signaling, mitigation of oxidative stress through Nrf2-mediated antioxidant responses, suppression of inflammation via NF-κB and TLR4 signaling, and attenuation of hepatic fibrosis via inhibition of the TGF-β/Smad pathway. Selected formulations also achieved adipose tissue targeting, thereby highlighting their potential to modulate liver-adipose tissue metabolic crosstalk. Despite these promising preclinical findings, clinical translation remains limited by methodological heterogeneity, inconsistent stability assessment, insufficient safety data, absence of clinical trials, biological barriers such as rapid mononuclear phagocyte system clearance, protein corona formation, and restricted penetration through the fibrotic extracellular matrix. Moreover, there are challenges in large-scale manufacturing and batch-to-batch reproducibility. Thus, rigorous toxicological evaluation and well-designed clinical trials are essential for facilitating the clinical translation of liposomal nanomedicines for treatment of liver diseases.