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  1. Gunathilake TMSU, Ching YC, Uyama H, Chuah CH
    J Drug Deliv Sci Technol, 2021 Aug;64:102634.
    PMID: 34127930 DOI: 10.1016/j.jddst.2021.102634
    Viral diseases have recently become a threat to human health and rapidly become a significant cause of mortality with a continually exacerbated unfavorable socio-economic impact. Coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have threatened human life, with immense accompanying morbidity rates; the COVID-19 (caused by SARS-CoV-2) epidemic has become a severe threat to global public health. In addition, the design process of antiviral medications usually takes years before the treatments can be made readily available. Hence, it is necessary to invest scientifically and financially in a technology platform that can then be quickly repurposed on demand to be adequately positioned for this kind of pandemic situation through lessons learned from the previous pandemics. Nanomaterials/nanoformulations provide such platform technologies, and a proper investigation into their basic science and biological interactions would be of great benefit for potential vaccine and therapeutic development. In this respect, intelligent and advanced nano-based technologies provide specific physico-chemical properties, which can help fix the key issues related to the treatments of viral infections. This review aims to provide an overview of the latest research on the effective use of nanomaterials in the treatment of coronaviruses. Also raised are the problems, perspectives of antiviral nanoformulations, and the possibility of using nanomaterials effectively against current pandemic situations.
  2. Gunathilake TMSU, Ching YC, Chuah CH, Hai ND, Nai-Shang L
    Pharm Res, 2020 Aug 30;37(9):178.
    PMID: 32864721 DOI: 10.1007/s11095-020-02910-z
    PURPOSE: Among various types of external stimuli-responsive DDS, electric-responsive DDS are more promising carriers as they exploit less complex, easily miniaturized electric signal generators and the possibility of fine-tuning the electric signals. This study investigates the use of intrinsically biocompatible biopolymers in electro-simulative drug delivery to enhance the release of poorly-soluble/non-ionic drug.

    METHODS: CMC/PLA/ZnO/CUR nanocomposite films were prepared by the dispersion of CMC and ZnO NPs in solubilized PLA/curcumin medium, followed by solvent casting step. Curcumin is poorly water-soluble and used as the model drug in this study. The films with different contents of CMC, PLA and ZnO NPs were characterized using FTIR, impedance spectroscopy, tensile testing and FESEM imaging. The in vitro drug release of the films was carried out in deionized water under DC electric field of 4.5 V.

    RESULTS: The ionic conductivity of the films increased with increasing the CMC concentration of the film. The addition of a small amount of ZnO NPs (2%) successfully restored the tensile properties of the film. In response to the application of the electric field, the composite films released drug with a near-linear profile. There was no noticeable amount of passive diffusion of the drug from the film with the absence of the electric field.

    CONCLUSION: The outcome of this study enabled the design of an electric-responsive nanocomposite platform for the delivery of poorly water-soluble/non-ionic drugs. Graphical abstract.

  3. Gunathilake TMSU, Ching YC, Uyama H, Nguyen DH, Chuah CH
    Int J Biol Macromol, 2021 Dec 15;193(Pt B):1522-1531.
    PMID: 34740692 DOI: 10.1016/j.ijbiomac.2021.10.215
    The investigation of protein-nanoparticle interactions contributes to the understanding of nanoparticle bio-reactivity and creates a database of nanoparticles for use in nanomedicine, nanodiagnosis, and nanotherapy. In this study, hen's egg white was used as the protein source to study the interaction of proteins with sulphuric acid hydrolysed nanocellulose (CNC). Several techniques such as FTIR, zeta potential measurement, UV-vis spectroscopy, compressive strength, TGA, contact angle and FESEM provide valuable information in the protein-CNC interaction study. The presence of a broader peak in the 1600-1050 cm-1 range of CNC/egg white protein FTIR spectrum compared to the 1600-1050 cm-1 range of CNC sample indicated the binding of egg white protein to CNC surface. The contact angle with the glass surface decreased with the addition of CNC to egg white protein. The FESEM EDX spectra showed a higher amount of N and Na on the surface of CNC. It indicates the density of protein molecules higher around CNC. The zeta potential of CNC changed from -26.7 ± 0.46 to -21.7 ± 0.2 with the introduction of egg white protein due to the hydrogen bonding, polar bonds and electrostatic interaction between surface CNC and protein. The compressive strength of the egg white protein films increased from 0.064 ± 0.01 to 0.36 ± 0.02 MPa with increasing the CNC concentration from 0 to 4.73% (w/v). The thermal decomposition temperature of CNC/egg white protein decreased compared to egg white protein thermal decomposition temperature. According to UV-Vis spectroscopy, the far-UV light (207-222nm) absorption peak slightly changed in the CNC/egg white protein spectrum compared to the egg white protein spectrum. Based on the results, the observations of protein nanoparticle interactions provide an additional understanding, besides the theoretical simulations from previous studies. Also, the results indicate to aim CNC for the application of nanomedicine and nanotherapy. A new insight given by us in this research assumes a reasonable solution to these crucial applications.
  4. Gunathilake TMSU, Ching YC, Uyama H, Hai ND, Chuah CH
    Cellulose (Lond), 2022 Jan 04.
    PMID: 35002106 DOI: 10.1007/s10570-021-04391-8
    Nanocellulose/polyvinyl alcohol/curcumin (CNC/PVA/curcumin) nanoparticles with enhanced drug loading properties were developed by the dispersion of nanocellulose in curcumin/polyvinyl alcohol aqueous medium. Due to the physical and chemical nature of sulphuric acid hydrolyzed nanocellulose and the antiviral properties of curcumin, the possibility of using these nanoparticles as an inhalable nanotherapeutic for the treatment of coronavirus disease 2019 (COVID-19) is discussed. The adsorption of curcumin and PVA into nanocellulose, and the presence of anionic sulphate groups, which is important for the interaction with viral glycoproteins were confirmed by Fourier transform infrared (FTIR) spectroscopy. FESEM images showed that the diameter of nanocellulose ranged from 50 to 100 nm, which is closer to the diameter (60-140 nm) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The solubility of poorly water-soluble curcumin was increased from 40.58 ± 1.42 to 313.61 ± 1.05 mg/L with increasing the PVA concentration from 0.05 to 0.8% (w/v) in aqueous medium. This is a significant increase in the solubility compared to curcumin's solubility in carboxymethyl cellulose medium in our previous study. The drug loading capacity increased by 22-fold with the addition of 0.8% PVA to the nanocellulose dispersed curcumin solution. The highest drug release increased from 1.25 ± 0.15 mg/L to 17.11 ± 0.22 mg/L with increasing the PVA concentration from 0 to 0.8% in the drug-loaded medium. Future studies of this material will be based on the antiviral efficacy against SARS-CoV-2 and cell cytotoxicity studies. Due to the particulate nature, morphology and size of SARS-CoV-2, nanoparticle-based strategies offer a strong approach to tackling this virus. Hence, we believe that the enhanced loading of curcumin in nanocellulose will provide a promising nano-based solution for the treatment of COVID-19.
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