Background: 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.
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.