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  1. Tan JM, Foo JB, Fakurazi S, Hussein MZ
    Beilstein J Nanotechnol, 2015;6:243-53.
    PMID: 25671168 DOI: 10.3762/bjnano.6.23
    This work explores the potential use of commercially obtained, carboxylated, single-walled carbon nanotubes (SWCNT-COOH) as nanocarriers for the antiparkinson drug, levodopa (LD). The resulting nanohybrid was characterized using materials characterization methods including Fourier transform infrared spectroscopy, Raman spectroscopy, elemental analysis, UV-vis spectroscopy and scanning electron microscopy. The results showed that SWCNT-COOH were able to form supramolecular complexes with LD via a π-π stacking interaction and exhibited favourable, slow, sustained-release characteristics as a drug carrier with a release period over more than 20 h. The results obtained from the drug release studies of LD at different pH values showed that the LD-loaded nanohybrid is pH activated. The release kinetics of LD from SWCNT-COOH were well-described by a pseudo-second-order kinetic model. A cytotoxicity assay of the synthesized nanohybrid was also carried out in PC12 cell lines (a widely used, in vitro Parkinson's model for neurotoxicity studies) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in order to investigate their possible effects on normal neuronal cells in vitro. It was found that the synthesized nanohybrid did not compromise the cell viability and the PC12 cells remained stable throughout the experiments up to 72 h after treatment.
  2. Tan JM, Karthivashan G, Arulselvan P, Fakurazi S, Hussein MZ
    Drug Des Devel Ther, 2014;8:2333-43.
    PMID: 25429205 DOI: 10.2147/DDDT.S70650
    Among the array of nanomaterials, carbon nanotubes have shown great potential as drug carriers in the field of nanomedicine, owing to their attractive physicochemical structure, which facilitates functionalization of therapeutic molecules onto their external walls or being encapsulated inside the tubes. The aim of this preliminary study was to formulate betulinic acid (BA), a poorly water-soluble drug, in oxidized multiwalled carbon nanotubes (MWCNT-COOH) for enhanced delivery efficiency into cancer cells with reduced cytotoxicity. The synthesized MWCNT-BA nanocomposite was characterized using ultraviolet-visible, Fourier transform infrared, thermogravimetric analysis, powder X-ray diffraction, and field emission scanning electron microscopy techniques. The loading of BA in MWCNT-COOH nanocarrier was estimated to be about 14.5%-14.8% (w/w), as determined by ultraviolet-visible and thermogravimetric analysis. Fourier transform infrared study shows that the peaks of the resulting MWCNT-BA nanocomposite correlate to the characteristic functional groups of BA and MWCNT-COOH. The powder X-ray diffraction results confirmed that the tubular structures of MWCNT-COOH were not affected by the drug loading mechanism of BA. The release profiles demonstrated that approximately 98% of BA could be released within 22 hours by phosphate-buffered saline solution at pH 7.4 compared with about 22% within 24 hours at pH 4.8. The biocompatibility studies revealed that MWCNT-BA at concentrations <50μg/mL expressed no cytotoxicity effects for mouse embryo fibroblast cells after 72 hours of treatment. The anticancer activity of MWCNT-BA was observed to be more sensitive to human lung cancer cell line when compared with human liver cancer cell line, with half maximal inhibitory concentration values of 2.7 and 11.0μg/mL, respectively. Our findings form a fundamental platform for further investigation of the MWCNT-BA formulation against different types of cancer cells.
  3. Tan JM, Parolia A, Pau AK
    BMC Oral Health, 2013;13:52.
    PMID: 24098931 DOI: 10.1186/1472-6831-13-52
    This study compared the effectiveness of a Specially Designed Paste Carrier technique with the Syringe-Spreader technique and the Syringe-Lentulo spiral technique in the intracanal placement of calcium hydroxide.
  4. Mohamad Isa MF, Tan JM, Abdul Aziz MF, Leong CL
    Med J Malaysia, 2018 12;73(6):405-406.
    PMID: 30647214
    Influenza outbreaks in tropical countries are rarely reported. This article reports four cases of influenza within a psychiatric ward of a tertiary hospital in Malaysia. These were patients with severe mental illness who were involuntarily admitted and did not show the classical triad of influenza-like-illness (ILI) at the beginning. However, severe respiratory complications developed requiring intubation. Referral and cooperation with the infectious disease team was initiated to help manage the outbreak while continuing psychiatric treatment. Incidences of influenza among hospitalised psychiatric patients should be treated seriously with immediate multidisciplinary approach to prevent severe unwanted complications.
  5. Tan JM, Bullo S, Fakurazi S, Hussein MZ
    Sci Rep, 2020 10 09;10(1):16941.
    PMID: 33037287 DOI: 10.1038/s41598-020-73963-8
    This research work represents the first major step towards constructing an effective therapeutic silibinin (SB) in cancer treatment using oxidised multi-walled carbon nanotubes (MWCNT-COOH) functionalised with biocompatible polymers as the potential drug carrier. In an attempt to increase the solubility and dispersibility of SB-loaded nanotubes (MWSB), four water-soluble polymers were adopted in the preparation process, namely polysorbate 20 (T20), polysorbate 80 (T80), polyethylene glycol (PEG) and chitosan (CHI). From the geometry point of view, the hydrophobic regions of the nanotubes were loaded with water-insoluble SB while the hydrophilic polymers functionalised on the outer surfaces of the nanotubes serve as a protective shell to the external environment. The chemical interaction between MWSB nanocomposites and polymer molecules was confirmed by Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. Besides, high-resolution transmission electron microscopy (HR-TEM), field emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA) and UV-visible spectrophotometry were also employed to characterise the synthesised nanocomposites. The morphological study indicated that the polymers were deposited on the external surfaces of MWSB and the nanocomposites were seen to preserve their tubular structures even after the coating process was applied. The TGA results revealed that the incorporation of biopolymers practically improved the overall thermal stability of the coated MWSB nanocomposites. Evaluation of the in vitro effect on drug release rate by the nanocomposites was found to follow a biphasic release manner, showing a fast release at an initial stage and then a sustained-release over 2500 min. Besides, the drug release mechanisms of the nanocomposites demonstrated that the amount of SB released in the simulated environment was governed by pseudo-second order in which, the rate-limiting step mainly depends on diffusion of drug through chemisorption reaction. Finally, MTT assay showed that the coated MWSB nanocomposites on 3T3 cells were very much biocompatible at a concentration up to 100 g/mL, which is an evidence of MWSB reduced cytotoxicity.
  6. Tan JM, Karthivashan G, Abd Gani S, Fakurazi S, Hussein MZ
    J Mater Sci Mater Med, 2016 Feb;27(2):26.
    PMID: 26704543 DOI: 10.1007/s10856-015-5635-8
    Chemically functionalized carbon nanotubes are highly suitable and promising materials for potential biomedical applications like drug delivery due to their distinct physico-chemical characteristics and unique architecture. However, they are often associated with problems like insoluble in physiological environment and cytotoxicity issue due to impurities and catalyst residues contained in the nanotubes. On the other hand, surface coating agents play an essential role in preventing the nanoparticles from excessive agglomeration as well as providing good water dispersibility by replacing the hydrophobic surfaces of nanoparticles with hydrophilic moieties. Therefore, we have prepared four types of biopolymer-coated single walled carbon nanotubes systems functionalized with anticancer drug, betulinic acid in the presence of Tween 20, Tween 80, polyethylene glycol and chitosan as a comparative study. The Fourier transform infrared spectroscopy studies confirm the bonding of the coating molecules with the SWBA and these results were further supported by Raman spectroscopy. All chemically coated samples were found to release the drug in a slow, sustained and prolonged fashion compared to the uncoated ones, with the best fit to pseudo-second order kinetic model. The cytotoxic effects of the synthesized samples were evaluated in mouse embryonic fibroblast cells (3T3) at 24, 48 and 72 h. The in vitro results reveal that the cytotoxicity of the samples were dependent upon the drug release profiles as well as the chemical components of the surface coating agents. In general, the initial burst, drug release pattern and cytotoxicity could be well-controlled by carefully selecting the desired materials to suit different therapeutic applications.
  7. Tan JM, Saifullah B, Kura AU, Fakurazi S, Hussein MZ
    Nanomaterials (Basel), 2018 May 31;8(6).
    PMID: 29857532 DOI: 10.3390/nano8060389
    Four drug delivery systems were formulated by non-covalent functionalization of carboxylated single walled carbon nanotubes using biocompatible polymers as coating agent (i.e., Tween 20, Tween 80, chitosan or polyethylene glycol) for the delivery of levodopa, a drug used in Parkinson's disease. The chemical interaction between the coating agent and carbon nanotubes-levodopa conjugate was confirmed by Fourier transform infrared (FTIR) and Raman studies. The drug release profiles were revealed to be dependent upon the type of applied coating material and this could be further adjusted to a desired rate to meet different biomedical conditions. In vitro drug release experiments measured using UV-Vis spectrometry demonstrated that the coated conjugates yielded a more prolonged and sustained release pattern compared to the uncoated conjugate. Cytotoxicity of the formulated conjugates was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using normal mouse embryonic fibroblast 3T3 cell line. Compared to the non-coated conjugate, the MTT data indicated that the coating procedure improved the biocompatibility of all systems by 34⁻41% when the concentration used exceeded 100 μg/mL. In conclusion, the comprehensive results of this study suggest that carbon nanotubes-based drug carrier coated with a suitable biomaterial may possibly be a potential nanoparticle system that could facilitate drug delivery to the brain with tunable physicochemical properties.
  8. Tan JM, Karthivashan G, Gani SA, Fakurazi S, Hussein MZ
    Chem Cent J, 2016;10:81.
    PMID: 28028386 DOI: 10.1186/s13065-016-0228-2
    In this paper, we demonstrate the preparation of silibinin-loaded carbon nanotubes (SWSB) with surface coating agents via non-covalent approach as an effective drug delivery system. The resulting surface-coated SWSB nanocomposites are extensively characterized by Fourier transform infrared (FTIR) and Raman spectroscopies, ultraviolet-visible (UV-Vis) spectrometry and field emission scanning electron microscopy (FESEM). The FTIR and Raman studies show that an additional layer is formed by these coating agents in the prepared nanocomposites during the coating treatment and these results are confirmed by FESEM. Drug loading and release profiles of the coated SWSB nanocomposites in phosphate buffered saline solution at pH 7.4 is evaluated by UV-Vis spectrometry. The in vitro results indicate that the surface-modified nanocomposites, with SB loading of 45 wt%, altered the initial burst and thus, resulted in a more prolonged and sustained release of SB. In addition, these nanocomposites exhibit a pseudo-second-order release kinetic which was driven by the ion exchange between the ionized SWSB and the anions in the release medium. The cytotoxicity effect of the resulting nanocomposites on normal mouse fibroblast cells is evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that the surfactant and polymer coating improved the biocompatibility of the SWSB nanocomposites significantly, which deem further exploitation for their application as potential anticancer drug delivery system.
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