Poly(3-hydroxybutyrate)/poly(amine)-coated nickel oxide nanoparticles for norfloxacin delivery: antibacterial and cytotoxicity efficiency

Abstract

Sustained release dosage forms enable prolonged and continuous release of a drug in the gastrointestinal tract for medication characterized by a short half lifetime. In this study, the effect of blending polyamine on poly(3-hydroxybutyrate) (PHB) as a carrier for norfloxacin (NF) was studied. The prepared blend was mixed with different amounts of NiO nanoparticles and characterized using FTIR analysis, X-ray diffraction analysis, thermogravimetric analysis, dynamic light scattering, transmission electron microscopy and scanning electron microscopy. It was found that the drug released from the nanocomposite has a slow rate in comparison with NiO, PHB, and PHB/polyamine blend. The highest ratio of NiO content to the matrix (highest NF loading), leads to a slower rate of drug release. The release from the nanocomposites showed a faster rate at pH = 2 than that at pH = 7.4. The mechanisms of NF adsorption and release were studied on PHB/polyamine-3% NiO nanocomposite. In addition, the antimicrobial efficacy of nanocomposites loaded with the drug was determined and compared with the free drug. Inclusion of NiO into PHB/polyamine showed a higher efficacy against Streptococcus pyogenes and Pseudomonas aeruginosa than the free NF. Moreover, the cytotoxicity of PHB/polyamine-3% NiO against HePG-2 cells was investigated and compared with PHB and PHB/polyamine loaded with the drug. The most efficient IC₅₀ was found for NF@PHB/polyamine-3% NiO (29.67 μg mL^-1). No effect on cell proliferation against the normal human cell line (WISH) was observed and IC₅₀ was detected to be 44.95 and 70 μg mL^-1 for NiO nanoparticles and the PHB/polyamine-3% NiO nanocomposite, respectively indicating a selectivity of action towards tumor cells coupled with a lack of cytotoxicity towards normal cells.

Fig. 1. (I) FTIR spectra of (a) neat PHB, (b) polyamine, (c) PHB/polyamine, (d) PHB/polyamine–1% NiO, (e) PHB/polyamine–3% NiO, and (f) neat PHB/polyamine–5% NiO; (II) XRD pattern of (a) NiO, (b) neat PHB, (c) PHB/polyamine, (d) PHB/polyamine–1% NiO, (e) PHB/polyamine–3% NiO, and (f) PHB/polyamine–5% NiO; (III) TGA of (a) PHB, (b) PHB/polyamine–1% NiO, (c) PHB/polyamine–3% NiO, and (d) PHB/polyamine–5% NiO.

Fig. 2. SEM images of PHB/polyamine–1% NiO (A), PHB/polyamine–5% NiO (B) and EDX analysis plot of PHB/polyamine–3% NiO (C); TEM of PHB/polyamine–3% NiO (D).

Fig. 3. NF Loading (%) onto (a) NiO, (b) PHB, (c) PHB/polyamine, (d) PHB/polyamine–1% NiO, (e) PHB/polyamine–3% NiO and (f) PHB/polyamine–5% NiO using 16 ppm NF.

Fig. 4. Loading (%) of different concentration of NF onto PHB/polyamine–3% NiO nanocomposites.

Fig. 5. Pseudo-first order (A), pseudo-second order (B) and intra-particle diffusion model (C) Langmuir (D), Freundlich (E) and Temkin (F) isotherms of NF@PHB/polyamine–3% NiO nanocomposites.

Fig. 6. In vitro release of NF from NiO (A), neat PHB (B), PHB/polyamine (C), PHB/polyamine–1% NiO (D), PHB/polyamine–3% NiO (E), and PHB/polyamine–5% NiO nanocomposites (F) in buffer solution at pH = 2, 7.4.

Fig. 7. (A) Zero-order, (B) first-order, (C) Higuchi, (D) Hixson–Crowell and (E) Korsmeyer–Peppas kinetic equations of NF from NiO at pH = 2 and 7.4.

Fig. 8. (A) Zero-order, (B) first-order, (C) Higuchi, (D) Hixson–Crowell and (E) Korsmeyer–Peppas kinetic equations of NF from PHB/polyamine–3% NiO at pH = 2 and 7.4.

Fig. 9. (A) Relative viability of cells at different concentration; (B) cytotoxicity of NiO and PHB/polyamine–3% NiO on normal cell (WISH) expressed as 50% inhibitory concentration (μg m⁻¹).