Targeting liver cancer via ASGP receptor using 5-FU-loaded surface-modified PLGA nanoparticles

Abstract

Context: Liver cancer is widespread liver malignancy in the world, for an estimated one million deaths annually. Objective: In present work, lactobionic acid conjugated PLGA nanoparticles (LDNPs) bearing 5-Fluorouracil (5-FU) were developed for targeted delivery to hepatocellular carcinoma. Materials and methods: Lactobionic acid conjugated PLGA was used to prepare LDNPs using modified emulsion diffusion method. Results: They were characterised for particle morphology, particle size (below 150 nm), zeta potential and polydispersity index (PDI ∼0.35), entrapment efficiency (∼60.23%), and cumulative percent drug release. Discussion: LDNPs in ex-vivo cell line studies on human cancer cell line HepG2 exhibited significantly higher cytotoxicity compared to 5-FU and DNPs (unconjugated PLGA NPs) with growth inhibition 50% (GI₅₀) of 66.7 µg/mL, 50.2 µg/mL and 35.5 µg/mL, respectively. In vivo studies exhibited higher drug concentration about 37.52 ± 0.68% in liver as compared to other organs and plasma. Conclusion: Thus, LDNPs showed high drug loading, specificity, biocompatibility and efficacy in treatment of liver cancer.

• 5-FU
• ASGP
• HePG2
• liver cancer
• PLGA

Acknowledgements

The authors are thankful to AIIMS (New Delhi) and Panjab University (Chandigarh) for SEM, TEM studies, and ACTREC (Tata Memorial Centre, Mumbai) for cell line studies. The authors especially Pooja Hurkat, Ankit Jain and Ashish Jain would like to acknowledge Council of Scientific and Industrial Research for their financial support.