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

Abstract

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