Development, optimization and Characterization of novel Cetuximab conjugated, Lycopene encapsulated PLGA-Alginate nanoparticles for an enhanced cytotoxicity of Lycopene in PANC-1 cells

Abstract

This study aims to mitigate pancreatic cancer by developing Cetuximab-conjugated Sodium Alginate- Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Lycopene. Although Lycopene, a strong antioxidant found in tomatoes, has shown strong anti-cancer effects, its poor solubility and stability limit its therapeutic use. Lycopene is encapsulated in nanoparticles made of a hybrid combination of Sodium Alginate and PLGA matrix which Alginate increases the encapsulation efficacy of Lycopene, increases its solubility and guarantees a regulated release. To attain the required particle size, zeta potential, and drug encapsulation effectiveness, a number of factors were methodically adjusted by using Design of expert software and following the Box Behenken design, including the formulation's stirring speed (rpm) and the content of Sodium Alginate and surfactant (Tween 80). The formulationshowed a negative zeta potential, a good drug loading and encapsulation capacity, and an average particle size of roughly 154 nm. The optimised nanoparticles was conjugated with Cetuximab and the amount conjugated monoclonal antibody was estimated using Bradford’s protein assay. Moreover, the haemolytic toxicity study indicated a compatible nature of the formulation with RBC’s with no evident hemolysis. Finally, the optimized formulation showed and enhanced cytotoxicity in PANC-1 cell linens in comparison to pure Lycopene. We attribute this to the fact that the optimized formulation showed an enhanced cellular uptake and better cellular internalization, making it a very promising drug delivery tool for Pancreatic ductal adenocarcinoma.