The smart nanocarrier containing zein/starch co-biopolymers enhanced by graphitic carbon nitride; exploring opportunities in brain cancer treatment

• Published in: International journal of biological macromolecules 2024-08, Vol.274 (Pt 1), p.133275, Article 133275
• Main Authors: Pourmadadi, Mehrab, Poorkhalili, Pegah, Sorourian, Maral, Sorourian, Ghazal, Ghaderi, Reza, Mehrabi, Mohammadamin Ghasem, Ajalli, Narges
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Biopolymers - chemistry; Brain Neoplasms - drug therapy; Cell Line, Tumor; Drug Carriers - chemistry; Drug delivery system; Drug Liberation; Fluorouracil - chemistry; Fluorouracil - pharmacology; Graphite - chemistry; Graphitic carbon nitride; Humans; Hydrogen-Ion Concentration; Nanocomposites - chemistry; Nitrogen Compounds - chemistry; pH-sensitive nanocarrier; Starch; Starch - chemistry; Zein; Zein - chemistry
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.133275

In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy. The nanocomposite containing zein (Z), starch (S), and graphitic carbon nitride (g-C3N4) macromolecules is synthesized by a water-in-oil-in-water (W/O/W) double emulsion technique, serving as a carrier for 5-FU. The S/Z hydrogel matrix's entrapment and loading efficiency are greatly improved by adding g-C3N4 nanosheets, reaching noteworthy values of 45.25 % and 86.5 %, respectively, for drug loading efficiency and entrapment efficiency. Characterization through FTIR and XRD validates the successful loading of 5-FU, elucidating the chemical bonding within the nanocomposite and crystalline characteristics. Structural analysis using FESEM, along with DLS and zeta potential measurements, reveals an average nanocomposite size of 193.48 nm, indicating a controlled structure, and a zeta potential of −42.32 mV, signifying a negatively charged surface. Studies on the in vitro release of drugs reveal that 5-FU is delivered more effectively and sustainably in acidic environments than in physiological circumstances. This highlights the fact that the created nanocarrier is pH-sensitive. Modeling release kinetics involves finding the right mathematical conditions representing underlying physicochemical processes. Employing curve-fitting techniques, predominant release mechanisms are identified, and optimal-fitting kinetic models are determined. The Baker kinetic model performed best at pH 7.4, indicating that the leading cause of the drug release was polymer swelling. In contrast, the Higuchi model was most accurate for drug release at pH 5.4, illuminating the diffusion and dissolution mechanisms involved in diffusion. To be more precise, the mechanism of release at pH 7.4 and 5.4 was anomalous transport (dissolution-controlled), according to the Korsmeyer-Peppas mathematical model. The pH-dependent swelling and degradation behavior of S/Z/g-C3N4@5-FU nanocomposite showed higher swelling and faster degradation in acidic environments compared to neutral conditions. Crucially, outcomes from the MTT test affirm the significant cytotoxicity of the 5-FU-loaded nanocomposite against U-87 MG brain cancer cells, while simultaneously indicating non-toxicity towards L929 fibroblast cells. These cumulative findings underscore the potential of the engineered S/Z/g-C3N4@5-FU as a productive and targeted therapeutic