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Enhanced Activity and Sustained Release of Protocatechuic Acid, a Natural Antibacterial Agent, from Hybrid Nanoformulations with Zinc Oxide Nanoparticles.

ABSTRACT: Hybrid nanostructures can be developed with inorganic nanoparticles (NPs) such as zinc oxide (ZnO) and natural antibacterials. ZnO NPs can also exert antibacterial effects, and we used them here to examine their dual action in combination with a natural antibacterial agent, protocatechuic acid (PCA). To produce hybrid nanoformulations, we functionalized ZnO NPs with four types of silane organic molecules and successfully linked them to PCA. Physicochemical assessment confirmed PCA content up to ~18% in hybrid nanoformulations, with a PCA entrapment efficiency of ~72%, indicating successful connection. We then investigated the in vitro release kinetics and antibacterial effects of the hybrid against Staphylococcus aureus. PCA release from hybrid nanoformulations varied with silane surface modification. Within 98 h, only 8% of the total encapsulated PCA was released, suggesting sustained long-term release. We used nanoformulation solutions collected at days 3, 5, and 7 by disc diffusion or log reduction to evaluate their antibacterial effect against S. aureus. The hybrid nanoformulation showed efficient antibacterial and bactericidal effects that also depended on the surface modification and at a lower minimum inhibition concentration compared with the separate components. A hybrid nanoformulation of the PCA prodrug and ZnO NPs offers effective sustained-release inhibition of S. aureus growth.

SUBMITTER: AbouAitah K

PROVIDER: S-EPMC8156785 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:At present, antibiotic resistance is one of the most pressing issues in healthcare globally. The development of new medicine for clinical applications is significantly less than the emergence of multiple drug-resistant bacteria, thus modification of existing medicines is a useful avenue. Among several approaches, nanomedicine is considered of potential therapeutic value. Herein, we have synthesized Zinc oxide nanoparticles (ZnO-NPs) conjugated with clinically-approved drugs (Quercetin, Ceftriaxone, Ampicillin, Naringin and Amphotericin B) with the aim to evaluate their antibacterial activity against several Gram-positive (Methicillin resistant Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes) and Gram-negative (Escherichia coli K1, Serratia marcescens and Pseudomonas aeruginosa) bacteria. The nanoparticles and their drug conjugates were characterized using UV-visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy and atomic force microscopy. Antibacterial activity was performed by dilution colony forming unit method and finally 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine their cytotoxic effects against human cell lines. ZnO-NPs revealed maxima surface plasmon resonance band at 374 and after conjugation with beta-cyclodextrin at 379 nm, polydispersity with size in range of 25-45 nm with pointed shaped morphology. When conjugated with ZnO-NPs, drug efficacy against MDR bacteria was enhanced significantly. In particular, Ceftriaxone- and Ampicillin-conjugated ZnO-NPs exhibited potent antibacterial effects. Conversely, ZnO-NPs and drugs conjugated NPs showed negligible cytotoxicity against human cell lines except Amphotericin B (57% host cell death) and Amphotericin B-conjugated with ZnO-NPs (37% host cell death). In conclusion, the results revealed that drugs loaded on ZnO-NPs offer a promising approach to combat increasingly resistant bacterial infections.

Project description:Owing to the peculiar broad-spectrum antimicrobial activities of zinc oxide nanoparticles (ZnO NPs), we envisaged their use to treat bacterial/mycobacterial/fungal infections during peritoneal dialysis (PD) of end-stage renal failure patients. However, a recent study from our lab showed that ZnO-NPs cannot be employed for the same in their naked form owing to their rapid agglomeration. Also, the naked ZnO-NPs showed strong interaction with organic acids present in the PD fluid (i.e., lactate and citrate present abundantly in almost all biological fluids) resulting in the formation of bioconjugates. Here, we propose that the surface coating of ZnO NPs may inhibit the binding interactions of NPs with the constituents of PD fluid. Therefore, in this study, we have carried out the surface coating of ZnO NPs with polyethylene glycol (PEG) of different molecular weights, followed by the investigations of physicochemical properties of PEGylated ZnO NPs dispersed in PD fluid using nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. The interaction of PEGylated ZnO NPs has also been studied separately in glucose and lactic acid which are the main constituents of PD fluid and in citric acid. Although the X-ray diffraction and TEM results infer the colloidal stability of PEGylated ZnO NPs in PD fluid, FT-IR, UV-vis, and nuclear magnetic resonance results revealed the binding interactions of PEGylated ZnO NPs with the PD constituents. PEGylated ZnO NPs also interact strongly with the lactic acid and citric acid, leading to agglomeration, as observed previously for uncoated ZnO NPs. Further, the antibacterial activities of bare and PEG-coated ZnO NPs dispersion in PD fluid have been studied. A reduction in the bacterial inhibition effect against Staphylococcus aureus and Escherichia coli was observed for both the bare and PEG-coated ZnO NPs dispersed in PD fluid, indicating that the complex nature of PD fluid counteract on the efficiency of these nanobiotics.

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Enhanced Activity and Sustained Release of Protocatechuic Acid, a Natural Antibacterial Agent, from Hybrid Nanoformulations with Zinc Oxide Nanoparticles.

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