Engineering baicalin-encapsulated PCL-PEG nanoparticles for enhanced anti-colorectal cancer applications

An advanced polymeric system was developed to overcome the limitations of poor solubility and bioavailability associated with baicalin, a natural flavonoid glycoside derived from Scutellaria baicalensis , by employing an emulsification–solvent diffusion method to formulate a novel drug delivery vehicle. The optimized formulation exhibited a uniform mean particle size of 158 ± 12 nm, a narrow polydispersity index (PDI) of 0.21, and a zeta potential of –18 ± 3 mV, ensuring stable dispersion. High encapsulation efficiency was achieved, reaching up to 92% across multiple batches. In vitro release studies demonstrated a pH-responsive behavior; approximately 35% of the drug was released in simulated gastric fluid (SGF) (pH 1.2) and nearly 70% in simulated intestinal/colonic fluid (pH 6.8–7.4) within 24 h. Kinetic analysis revealed that the Korsmeyer–Peppas model provided the best fit to the release data, indicating a diffusion-controlled release under acidic conditions and a combination of diffusion and polymer relaxation mechanisms at neutral pH, supporting controlled and sustained release behavior. Cellular internalization experiments confirmed dose-dependent uptake, with maximum uptake rates of 62% in HCT116 and 58% in HT29 cells, while cytotoxicity assays revealed significantly lower IC50 values (12 μg/mL in HCT116 and 15 μg/mL in HT29) compared to free drug formulations (20 μg/mL and 25 μg/mL, respectively). Furthermore, flow cytometry analysis showed a marked increase in apoptotic populations, with Sub-G1 fractions rising from 5.2% to 24.8% and overall apoptotic rates reaching 38% post-treatment. These findings suggest that the engineered delivery system provides enhanced therapeutic efficacy through improved bioavailability, targeted cellular uptake, and effective induction of apoptosis for advanced treatment strategies. Overall, the results underscore the significance of material engineering in optimizing physicochemical properties and therapeutic outcomes for improved efficacy. This innovative platform demonstrates strong potential for future comprehensive preclinical investigations, which are necessary to further assess its safety and efficacy before considering clinical applications.