Development and Optimization Naringenin Nanoparticle for Effective Therapy in Pancreatic Cancer

Background and Aim: Despite nanomedicines, advances in cancer therapy, pancreatic cancer continues to be the life
threatening disease in United States and other countries. The new cases of pancreatic cancer diagnosed in 2018 stand
at 460,000. The aim of the study was optimization, in vitro characterization, cytotoxic assessment and stability of
naringenin loaded nanoparticles (NPs).

Methods: The sonication tailored Naringenin (NARG)-loaded polymeric NPs were fabricated by emulsion diffusion
evaporation technique. Box Behnken experimental design based on 3-level and 3-factors was applied for optimization
of fabrication parameters. The effect of independent variables such as surfactant concentration (X1), polymer conc.
(X2), and sonication time (X3) were studied on responses particle size (Y1), and drug release % (Y2). NPs were
characterized for particles size and size distribution, polydispersity index (PDI), zeta potential, transmission electron
microscope (TEM), scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential
scanning calorimeter (DSC), and X-ray diffraction (XRD) studies. Drug release kinetics and cytotoxicity assays were also
carried out.

Results: The nanosized particles were spherical, uniform with an average size of 160 ± 23 nm, PDI value 0.210 ± 0.032,
zeta potential 25 ± 5.76 mV, and cumulative percentage release 82.21 ± 9.31%. In vitro release of NARG from
nanoparticle evaluated initially showed burst effect followed by sustained release behavior. The formulation followed
Higuchian model to drug release from NARG NPs. The MTT assay revealed that NARG NPs showed higher cytotoxic
effect over free NARG (p=0.045). The stability study of optimized formulation revealed no significant physicochemical
changes during 3 months of study.

Conclusion: NARG-loaded NPs have more potential in ameliorating cancer over NARG suspension.