Research Article For reprint orders, please contact: reprints@futuremedicine.com Tannic acid and vitamin E loaded PLGA nanoparticles ameliorate hepatic injury in a chronic alcoholic liver damage model via EGFR-AKT-STAT3 pathway Sayoni Nag 1 , Krishnendu Manna 1 , Moumita Saha 1 & Krishna Das Saha* ,1 1 Cancer Biology & Infammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, West Bengal, Kolkata-700032, India *Author for correspondence: Tel.: +91 33 2499 5810; Fax: +91 33 2473 5197; krishna@iicb.res.in Aim: Tannic acid and vitamin E loaded-poly D, L-lactide-co-glycolic acid (PLGA) nanoparticles (NP) were de- veloped to achieve hepatoprotection in alcoholic liver disease mice model. Materials & methods: PLGA NPs were formed by emulsion solvent evaporation and characterized and delivered to mice. Histology studies were performed, serum enzyme levels of AST, ALT and infammatory cytokines were checked using ELISA kits. Confocal microscopy and western blot analysis were utilized to determine protein expression levels, and docking studies were performed for interaction analysis. Results: PLGA NPs provided hepatoprotec- tion by reducing infammatory load, preventing reactive oxygen species generation and apoptosis, as well as by inhibiting the EGFR-AKT-STAT3 pathway. Conclusion: PLGA NPs of tannic acid and vitamin E could be a future medication for alcoholic liver disease treatment. Graphical abstract: OH OH OH OH OH OH OH OH OH OH OH OH HO HO HO HO HO HO HO HO HO HO HO HO HO O O O O O O O O O O O O O O O O O O O O O CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 O H 3 C O C O (CH 2 ) 2 COO(CH 2 CH 2 O)nH Tannic acid and vitamin E TPG loaded PLGA nanoparticles delivered intraperitoneally Vitamin E-TPGS Tannic acid Hepatic enzyme regulation SGPT↓, SGOT↓, AP↓, HDL↑, LDL↓, TG↓, TC↓ Hepatic anti-fibrotic, ant-inflammatory function TGF-β↓, IL-1β↓, TNF-α↓, IL-6↓, iNOS↓, Cox-2↓ Hepatic anti-oxidative function GP-x↑, Catalase↑, SOD↓, Nrf2↑ Hepatic anti-apoptotic function BAx↓, Bad↓, Bcl2↑, procaspase 3↓, caspase 3↓, caspase 9↓, cytochrome C↓ Hepato-protection offered via inhibition of: PLGA nanoparticles EGFR RAS RAF-1 MEK 1/2 ERK1/2 STAT-3 PI3K AKT1/2/3 P-AKT1/2/3 mTOR Tannic acid + Vitamin E-TPGS Alcoholic Liver Disease ROS↓ First draft submitted: 11 September 2019; Accepted for publication: 18 November 2019; Published online: 2 December 2019 Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889 10.2217/nnm-2019-0340 C  2019 Future Medicine Ltd