Preparation, Characterization and Antiviral Evaluation of Nano-formulations Comprising Curcumin-PLGA and Curcumin-metal Oxide Nanocomposite against SARS-CoV-2

Abstract

Background

Our current control strategies for viral infections still fall short of meeting the increasing demand for effective antiviral treatments. The evolving nature of viruses through genetic mutations often renders specific drugs ineffective against emerging strains. This research focuses on harnessing the potential of nanotechnology to develop more efficacious treatments using natural drug compounds. Curcumin, derived from Curcuma longa, is renowned for its broad therapeutic effects due to its ability to interact with various enzymes and proteins in the body. While curcumin can bind to viral proteins and inhibit their activity, it has inadequate bioavailability due to its low solubility in the aqueous gastrointestinal fluids. In contrast, curcumin nanoparticles offer improved solubility and bioavailability, enhancing our traditional approaches to control viral infections, including pandemics. Herein, curcumin nanoparticle formulations were generated using two different Curcumin nanoformulations. Specifically, curcumin was loaded onto Poly Lactic-co-Glycolic Acid (PLGA) to create the first nanoparticle Cur-PLGA. In parallel, Curcumin was combined with Zinc oxide to produce a Cur-ZnO composite. The compositions of these preparations, varying in curcumin concentrations, were verified through a series of physical and chemical assays, and then compared for their anti-SARS-CoV-2 activity.

Results

In vitro experiments revealed that the Cur-ZnO composite exhibited significantly higher anti-SARS-CoV-2 activity than Cur-PLGA, while maintaining host cell safety. Our investigation revealed that Zinc oxide surpasses PLGA in terms of Curcumin loading efficiency, significantly enhancing the effectiveness of the prepared samples across various applications. Furthermore, Cur-ZnO maintains an elevated level of safety, in contrast to the costly PLGA.

Conclusion

This study highlights the superiority of Cur-ZnO composite nanoparticles over Cur-PLGA as anti-SARS-CoV-2. It also emphasizes the robust antiviral potential of different curcumin based ZnO nanoparticles. Despite that this work highlights the significance of using the predefined nano-formulations as antivirals against SARS-CoV-2, this research primarily concentrates on the in vitro anti-viral effects. Therefore, further investigation through preclinical and clinical studies to validate these findings in vivo are still required.

Graphical Abstract

The graph clearly shows the advantage of Cur-ZnO nanoparticles over Cur-PLGA nanoparticles with a directly proportional relationship between the amount of curcumin in Cur-ZnO composite and its antiviral effect on SARS-CoV-2. The graph also illustrates the authors view about the structure of the prepared samples according to the characterizations where PLGA polymer was represented as a linear molecule, Curcumin was represented as yellow dots and ZnO was represented as hexagonal shape according to XRD analysis and HR-TEM imaging. The prepared samples are represented with respect to the previous single molecules representations as follow: Cur-PLGA representation was drew as if it is a transition section in the Cur-PLGA molecule to help in clarification of the encapsulation happened in the non-stoichiometric sample. The graph shows a hollow ring for the stoichiometric sample and a solid one for the non-stoichiometric sample. When we turn to Cur-ZnO samples as the amount of curcumin increases, it shows more yellow Curcumin dots in the hexagonal ZnO nanoparticles.