Anti-EGFR-mAb and 5-Fluorouracil Conjugated Polymeric Nanoparticles for Colorectal Cancer

Due to the higher intake of junk food and unhealthy lifestyle, the percentage of U.S. adults aged 50 to 75 years who were up-to-date with colorectal cancer screening increased 1.4 percentage points, from 67.4% in 2016 to 68.8% in 2018. This represents an additional 3.5 million adults screened for colorectal cancer. This is a severe concern of this research, and an attempt was made to prepare a target-specific formulation that could circumvent chemotherapy-related compilation and improvise higher cellular uptake. The fundamental agenda of this research was to prepare and develop Anti-EGFR mAb and 5-Fluorouracil (5-FU) fabricated polymeric nanoparticles for colorectal cancer.

The main objective of this research was to prepare and evaluate more target specific formulation for the treatment of colorectal cancer. PLGA and PEG-based polymeric nanoparticles are capable of preventing opsonization via the reticuloendothelial system. Hence, prepared polymeric nanoparticles are capable of higher cellular uptake.

The Poly(d,1-lactide-co-glycolide) (PLGA) and Polyethylene Glycol (PEG) were combined utilizing the ring-opening polymerization method. The presence of PEG prevents opsonization and distinguished blood concentration along with enhanced targeting. The presence of PLGA benefits in the sustained release of polymeric formulations. The optimized formulation (5-FU-PLGA- PEG-NP) was lyophilized using 4% trehalose (cryoprotectants) and conjugated with Anti- EGFR mAb on its surface to produce Anti-EGFR-5-FU-PLGA-PEG-NP; the final formulation, which increases target specificity and drug delivery system of nanoparticles.

The spherical shaped optimized formulation, 5-FU-PLGA-PEG-NP-3 was found to have higher percentage drug entrapment efficacy (71.23%), higher percentage drug content (1.98 ± 0.34%) with minimum particles size (252.3nm) and anionic zeta potential (-31.23mV). The IC₅₀ value of Anti-EGFR-5-FU-PLGA-PEG-NP was 1.01μg/mL after 48 hours incubation period in the HCT 116 cell line, indicating higher anticancer effects of the final formulation.

From the outcomes of various experiments, it was concluded that Anti-EGFR-5-FUPLGA- PEG-NP has biphasic drug release kinetics, higher cellular uptake and higher cytotoxicity. Therefore, anti-EGFR-5-FU-PLGA-PEG-NP holds excellent potential for drug delivery to EGFR positive colorectal cancer cells.