Smart Oral pH-Responsive Dual Layer Nano-Hydrogel for Dissolution Enhancement and Targeted Delivery of Naringenin Using Protein-Polysaccharides Complexation Against Colorectal Cancer

Naringenin (NAR) is a natural anticancer, but it has not been developed for clinical use despite its therapeutic potential due to its low water solubility, low membrane permeability, first-pass metabolism, and low bioavailability. To overcome these problems, the optimization and preparation of NAR-Soy protein complex (NAR-Sp) led to the optimum ratio of their interaction using Fourier Transform-Infrared spectroscopy (FT-IR) as the first level and layer of the formulation. The second layer of the formulation was to incorporate the NAR-Sp complex in aqueous-based gel-forming. The most optimum nanosuspension was determined using the gel sedimentation, sustained-release, pH-selective and targeted system. The most optimum components combinations and complex were characterized using different characterization tools, such as, the particle size analysis, SEM, TEM, PXRD and FT-IR. In addition, the optimum nanosuspension was characterized for its nanoparticle sensitivity against colorectal cancer cells using MTT assay in comparison to the untreated, naringenin, and blank groups. The complex enhanced the NAR's dissolution. The complex incorporation in the optimum nano-encapsulating system was characterized by the sustained-release and pH-selective behaviors to target the NAR release at the site of action or absorption. Interestingly, the optimum nano-encapsulating system was showing better colorectal cytotoxicity results in comparison to the other groups.