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  1. Ahmad R, Kaus NHM, Hamid S
    Adv Exp Med Biol, 2020;1292:65-82.
    PMID: 30560443 DOI: 10.1007/5584_2018_302
    INTRODUCTION: Drug resistance has been a continuous challenge in cancer treatment. The use of nanotechnology in the development of new cancer drugs has potential. One of the extensively studied compounds is thymoquinone (TQ), and this work aims to compare two types of TQ-nanoformulation and its cytotoxicity toward resistant breast cancer cells.

    METHOD: TQ-nanoparticles were prepared and optimized by using two different formulations with different drugs to PLGA-PEG ratio (1:20 and 1:7) and different PLGA-PEG to Pluronic F68 ratio (10:1 and 2:1). The morphology and size were determined using TEM and DLS. Characterization of particles was done using UV-VIS, ATR-IR, entrapment efficiency, and drug release. The effects of drug, polymer, and surfactants were compared between the two formulations. Cytotoxicity assay was performed using MTS assay.

    RESULTS: TEM finding showed 96% of particles produced with 1:7 drug to PLGA-PEG were less than 90 nm in size and spherical in shape. This was confirmed with DLS which showed smaller particle size than those formed with 1:20 drug to PLGA-PEG ratio. Further analysis showed zeta potential was negatively charged which could facilitate cellular uptake as reported previously. In addition, PDI value was less than 0.1 in both formulations indicating monodispersed and less broad in size distribution. The absorption peak of PLGA-PEG-TQ-Nps was at 255 nm. The 1:7 drug to polymer formulation was selected for further analysis where the entrapment efficiency was 79.9% and in vitro drug release showed a maximum release of TQ of 50%. Cytotoxicity result showed IC50 of TQ-nanoparticle at 20.05 μM and free TQ was 8.25 μM.

    CONCLUSION: This study showed that nanoparticle synthesized with 1:7 drug to PLGA-PEG ratio and 2:1 PLGA-PEG to Pluronic F68 formed nanoparticles with less than 100 nm and had spherical shape as confirmed with DLS. This could facilitate its transportation and absorption to reach its target. There was conserved TQ stability as exhibited slow release of this volatile oil. The TQ-nanoparticles showed selective cytotoxic effect toward UACC 732 cells compared to MCF-7 breast cancer cells.

  2. Noor NS, Kaus NHM, Szewczuk MR, Hamid SBS
    Int J Mol Sci, 2021 Aug 30;22(17).
    PMID: 34502328 DOI: 10.3390/ijms22179420
    Thymoquinone has anti-cancer properties. However, its application for clinical use is limited due to its volatile characteristics. The current study aims to develop a polymeric nanoformulation with PLGA-PEG and Pluronics F68 as encapsulants to conserve thymoquinone's (TQ) biological activity before reaching the target sites. Synthesis of nanoparticles was successfully completed by encapsulating TQ with polymeric poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol) and Pluronics F68 (TQ-PLGA-PF68) using an emulsion-solvent evaporation technique. The size and encapsulation efficiency of TQ-PLGA-PF68 nanoparticles were 76.92 ± 27.38 nm and 94%, respectively. TQ released from these encapsulants showed a biphasic released pattern. Cytotoxicity activity showed that tamoxifen-resistant (TamR) MCF-7 breast cancer cells required a higher concentration of TQ-PLGA-PF68 nanoparticles than the parental MCF-7 cells to achieve IC50 (p < 0.05). The other two resistant subtypes (TamR UACC732 inflammatory breast carcinoma and paclitaxel-resistant (PacR) MDA-MB 231 triple-negative breast cell line) required a lower concentration of TQ-PLGA-PF68 nanoparticles compared to their respective parental cell lines (p < 0.05). These findings suggest that TQ encapsulation with PLGA-PEG and Pluronics F68 is a promising anti-cancer agent in mitigating breast cancer resistance to chemotherapeutics. In future studies, the anti-cancer activity of TQ-PLGA-PF68 with the standard chemotherapeutic drugs used for breast cancer treatment is recommended.
  3. Krishnamoorthy M, Ahmad NH, Amran HN, Mohamed MA, Kaus NHM, Yusoff SFM
    Int J Biol Macromol, 2021 Jul 01;182:1495-1506.
    PMID: 34019924 DOI: 10.1016/j.ijbiomac.2021.05.104
    Semiconductor materials have shown a good photocatalytic behaviour for the photodegradation of organic pollutants. In this work, maleated liquid natural rubber (MLNR) based hydrogel supported bismuth ferrite (BiFeO3) as photocatalyst was successfully synthesized by crosslinking with acrylic acid (AAc) assisted by the ultrasonication method to study the efficiency for the removal of methylene blue (MB) dye in wastewater. Response surface methodology (RSM) was used to optimize the parameters for adsorption of the methylene blue (MB) dye compound, whereby the effects of the initial concentration of MB and the adsorption time were examined to obtain a quadratic model for the respective hydrogel composite. The prepared composite sample was characterized by Fourier Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy-Energy Dispersive X-ray (SEM-EDX) and X-ray Diffraction (XRD) analysis. Remarkable improvement for removal of methylene blue (99% removal) was found within 3 h adsorption time with a MLNR/AAc-BiFeO3 hydrogel composite as compared to the pristine hydrogel. A synergistic mode of dye removal by adsorption and photodegradation is proposed. Based on the isotherm and kinetic study conducted, it was found that Freundlich isotherm model and a pseudo second-order kinetic model was best fitted for adsorption of MB dye. The MLNR/AAc-BiFeO3 composite maintains its removal efficiency after 5 cycles without the necessity of post-treatment separation. Therefore, it is crucial to note that the resultant low-cost MLNR/AAc-BiFeO3 hydrogel composite in this study offers excellent potential for water and wastewater treatment applications with improved recyclability and recovery.
  4. Sirelkhatim A, Mahmud S, Seeni A, Kaus NHM, Ann LC, Bakhori SKM, et al.
    Nanomicro Lett, 2015;7(3):219-242.
    PMID: 30464967 DOI: 10.1007/s40820-015-0040-x
    Antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. ZnO-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. ZnO is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered ZnO-NPs antibacterial activity including testing methods, impact of UV illumination, ZnO particle properties (size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), OH- (hydroxyl radicals), and O2 -2 (peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to ZnO-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions. These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on ZnO abrasive surface texture. One functional application of the ZnO antibacterial bioactivity was discussed in food packaging industry where ZnO-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of ZnO-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.
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