In vitro release kinetics of bioactive compounds (gallic acid, ellagic acid, and eugenol) from chitosan polymer and the bioactivity of herb-loaded chitosan–CuO nanocomposites

The biological efficacy of nanocomposites comprised of chitosan, CuO nanoparticles, and extracts of Phyllanthus emblica, and Syzygium aromaticum was studied. The study assessed the pH- and ionic strength-responsive controlled release of the bioactive compounds, gallic acid, ellagic acid and eugenol, from the chitosan biopolymer. Release data were fitted into zero-order, first-order, Korsmeyer-Peppas (KP), Peppas-Sahlin (PS), Higuchi, and Hixson-Crowell kinetic models to evaluate the release mechanism. According to KP and PS models (R² ≥ 0.96), release was governed by quasi-Fickian diffusion (n < 0.43), where the diffusion occurs along with the polymer relaxation and swelling. P.emblica-coated chitosan (PeC) composite exhibited a burst release at acidic media conditions, and a quasi-Fickian diffusion at pH 5.5-7.4. Higher ionic strength caused salting-in effects for PeC in 0.4 M media, resulting in a transiently increased release. In acidic conditions, diffusion-controlled release was observed for S.aromaticum-coated chitosan (SaC) composite, with the optimal release at pH 4 media. Release was facilitated by hydrophobic nanochannels at elevated pH (8.5-10) and ionic strength of 0.5 M NaCl. The PS model's relaxation contributions were significant at 0.4 M NaCl and 5 mg drug loading. Both composites demonstrated enhanced release at physiological conditions (0.1-0.2 M NaCl, pH 7.4). Sustained release of SaC was achieved in near-neutral/moderate ionic strength media, whereas PeC exhibited sustained release in acid/low ionic strength media. The PeC and SaC composites showed IC₅₀ values of 10.78 µg/mL and 19.27 µg/mL for the DPPH radical scavenging ability, respectively. Recorded IC₅₀ values for the egg albumin denaturation assay were 467 µg/mL and 390.44 µg/mL, respectively. The antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus showed maximum inhibition zones of 11.83 ± 0.06 mm (Chitosan: CuO 1:2), 12.67 ± 0.20 mm (1:4), 16.50 ± 0.09 mm (1:4), and 11.83 ± 0.08 mm (4:1), respectively. Among the herbal-coated samples, SaC exhibited the highest activity of 23.67 ± 2.84 mm against E. coli.