Chitosan Surface-Modified PLGA Nanoparticles Loaded with Cranberry Powder Extract as a Potential Oral Delivery Platform for Targeting Colon Cancer Cells

Nutraceutical cranberry powder extract (CBPE) has distinct polyphenols inhibiting colon cancer growth and proliferation. However, its oral therapeutic efficacy is hindered because of its low permeability. This study aims to formulate chitosan surface-modified PLGA nanoparticles (CS-PLGA NPs) for encapsulating CBPE and modulating its release rate, permeation, cell targeting, and, therefore, its cytotoxicity. A full 2(3) factorial design is employed to scrutinize the effect of lactide/glycolide ratio, PLGA weight, and stabilizer concentrations on entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimum formula (F4) shows spherical particles with a relatively high EE% (72.30 ± 2.86%), an appropriate size of 370.10 ± 10.31 nm, PDI; 0.398 ± 0.001, and ZP; −5.40 ± 0.21 mV. Alongside the ATR-FTIR outcomes, the chitosan surface-modified formula (CS-F4) demonstrates a significant increase in particle size (417.67 ± 6.77 nm) and a shift from negative to positive zeta potential (+21.63 ± 2.46 mV), confirming the efficiency of surface modification with chitosan. The intestinal permeability of F4 and CS-F4 is significantly increased by 2.19- and 3.10-fold, respectively, compared to the CBPE solution, with the permeability coefficient (P(app)) being 2.05 × 10(−4) cm/min and 2.91 × 10(−4) cm/min, for F4 and CS-F4, respectively, compared to the CBPE solution, 9.36 × 10(−5) cm/min. Moreover, CS-F4 evidences significant caspase-3 protein level expression stimulation and significant inhibition of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription-3 (STAT-3) protein expression levels, confirming the superiority of CS-F4 for targeting HT-29 cells. Briefly, CS-PLGA NPs could be regarded as a prosperous delivery system of CBPE with enhanced permeation, cell targeting, and antitumor efficacy.