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.

The development of multifunctional topical formulations that combine natural bioactives with therapeutic nanomaterials offers a promising route to improved wound healing and management. Carica papaya fruit latex powder and Aloe barbadensis Miller gel were incorporated as active ingredients into an ointment base consisting of ZnO nanoparticles, cassava starch, and white petroleum jelly to formulate a novel topical medication with enhanced biological properties. According to the 2,2-diphenyl-1-picrylhydrazyl antioxidant assay, IC ₅₀ values of Carica papaya latex, Aloe gel, and ZnO nanoparticles were 454.54, 312.50, and 490.82 μg/mL, respectively. Carica papaya latex powder showed a protease activity of 58.40 units/mg of the solid. The ointment base exhibited the lowest blood clotting index (3.57 ± 6.09%), suggesting strong coagulation potential, whereas ZnO showed the highest (22.26 ± 1.09%), indicating minimal clotting ability under the current experimental setup. Erythrocyte adsorption was also highest in the ointment base (84.10 ± 1.09%), reinforcing its strong interaction with blood components. Cassava starch and petroleum jelly displayed moderate Red Blood Cell (RBC) attachment percentages. Platelet adhesion with the ointment base (61.55 ± 1.09%) and cassava starch (53.97 ± 2.40%) showed better platelet interaction than ZnO (29.1 ± 4.08%). Hemolysis data indicated that petroleum jelly caused the highest RBC lysis at all concentrations, while the ointment base showed the lowest activity, indicating better hemocompatibility. Clotting time analysis further highlighted the ointment base and petroleum jelly as effective pro-coagulants (13.30 s and 13.34 s, respectively), whereas ZnO (18.34 min) and cassava starch (48.34 s) exhibited delayed clotting. The ointment in which the base: active ingredient ratio is 7:3, and within, Carica papaya latex: Aloe gel ratio 1:4, shows the maximum antibacterial activity against Staphylococcus aureus and Escherichia coli . The MBC/MIC ratios of the above ointment for the two organisms were lower than 4, suggesting a bactericidal effect. The time-kill curves show a gradual reduction in bacterial survival over time, with the most significant reduction observed in the ointment with the highest proportion of Aloe vera.