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Fulltext Inorganic nanolayers: structure, preparation, and biomedical applications

Saifullah B, Hussein MZ

Int J Nanomedicine, 2015;10:5609-33.
PMID: 26366081 DOI: 10.2147/IJN.S72330

Hydrotalcite-like compounds are two-dimensional inorganic nanolayers also known as clay minerals or anionic clays or layered double hydroxides/layered hydroxy salts, and have emerged as a single type of material with numerous biomedical applications, such as drug delivery, gene delivery, cosmetics, and biosensing. Inorganic nanolayers are promising materials due to their fascinating properties, such as ease of preparation, ability to intercalate different type of anions (inorganic, organic, biomolecules, and even genes), high thermal stability, delivery of intercalated anions in a sustained manner, high biocompatibility, and easy biodegradation. Inorganic nanolayers have been the focus for researchers over the last decade, resulting in widening application horizons, especially in the field of biomedical science. These nanolayers have been widely applied in drug and gene delivery. They have also been applied in biosensing technology, and most recently in bioimaging science. The suitability of inorganic nanolayers for application in drug delivery, gene delivery, biosensing technology, and bioimaging science makes them ideal materials to be applied for theranostic purposes. In this paper, we review the structure, methods of preparation, and latest advances made by inorganic nanolayers in such biomedical applications as drug delivery, gene delivery, biosensing, and bioimaging.
Fulltext Carbon Nanomaterials for the Treatment of Heavy Metal-Contaminated Water and Environmental Remediation

Baby R, Saifullah B, Hussein MZ

Nanoscale Res Lett, 2019 Nov 11;14(1):341.
PMID: 31712991 DOI: 10.1186/s11671-019-3167-8

Nanotechnology is an advanced field of science having the ability to solve the variety of environmental challenges by controlling the size and shape of the materials at a nanoscale. Carbon nanomaterials are unique because of their nontoxic nature, high surface area, easier biodegradation, and particularly useful environmental remediation. Heavy metal contamination in water is a major problem and poses a great risk to human health. Carbon nanomaterials are getting more and more attention due to their superior physicochemical properties that can be exploited for advanced treatment of heavy metal-contaminated water. Carbon nanomaterials namely carbon nanotubes, fullerenes, graphene, graphene oxide, and activated carbon have great potential for removal of heavy metals from water because of their large surface area, nanoscale size, and availability of different functionalities and they are easier to be chemically modified and recycled. In this article, we have reviewed the recent advancements in the applications of these carbon nanomaterials in the treatment of heavy metal-contaminated water and have also highlighted their application in environmental remediation. Toxicological aspects of carbon-based nanomaterials have also been discussed.
Fulltext Palm Kernel Shell as an effective adsorbent for the treatment of heavy metal contaminated water

Baby R, Saifullah B, Hussein MZ

Sci Rep, 2019 Dec 12;9(1):18955.
PMID: 31831850 DOI: 10.1038/s41598-019-55099-6

Heavy metal contamination in water causes severe adverse effects on human health. Millions of tons of kernel shell are produced as waste from oil palm plantation every year. In this study, palm oil kernel shell (PKS), an agricultural waste is utilized as effective adsorbent for the removal of heavy metals, namely; Cr6+, Pb2+, Cd2+ and Zn2+ from water. Different parameters of adsorptions; solution pH, adsorbent dosage, metal ions concentration and contact time were optimized. The PKS was found to be effective in the adsorption of heavy metal ions Cr6+, Pb2+, Cd2+ and Zn2+ from water with percentage removal of 98.92%, 99.01%, 84.23% and 83.45%, respectively. The adsorption capacities for Cr6+, Pb2+, Cd2+ and Zn2+ were found to be 49.65 mg/g, 43.12 mg/g, 49.62 mg/g and 41.72 mg/g respectively. Kinetics of adsorption process were determined for each metal ion using different kinetic models like the pseudo-first order, pseudo-second order and parabolic diffusion models. For each metal ion the pseudo-second order model fitted well with correlation coefficient, R2 = 0.999. Different isotherm models, namely Freundlich and Langmuir were applied for the determination of adsorption interaction between metal ions and PKS. Adsorption capacity was also determined for each of the metal ions. PKS was found to be very effective adsorbent for the treatment of heavy metal contaminated water and short time of two hours is required for maximum adsorption. This is a comprehensive study almost all the parameters of adsorptions were studied in detail. This is a cost effective and greener approach to utilize the agricultural waste without any chemical treatment, making it user friendly adsorbent.
Fulltext Controlled-release approaches towards the chemotherapy of tuberculosis

Saifullah B, Hussein MZ, Hussein Al Ali SH

Int J Nanomedicine, 2012;7:5451-63.
PMID: 23091386 DOI: 10.2147/IJN.S34996

Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization's 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18-24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages.
Fulltext The Impact of Magnesium-Aluminum-Layered Double Hydroxide-Based Polyvinyl Alcohol Coated on Magnetite on the Preparation of Core-Shell Nanoparticles as a Drug Delivery Agent

Ebadi M, Buskaran K, Saifullah B, Fakurazi S, Hussein MZ

Int J Mol Sci, 2019 Aug 01;20(15).
PMID: 31374834 DOI: 10.3390/ijms20153764

One of the current developments in drug research is the controlled release formulation of drugs, which can be released in a controlled manner at a specific target in the body. Due to the diverse physical and chemical properties of various drugs, a smart drug delivery system is highly sought after. The present study aimed to develop a novel drug delivery system using magnetite nanoparticles as the core and coated with polyvinyl alcohol (PVA), a drug 5-fluorouracil (5FU) and Mg-Al-layered double hydroxide (MLDH) for the formation of FPVA-FU-MLDH nanoparticles. The existence of the coated nanoparticles was supported by various physico-chemical analyses. In addition, the drug content, kinetics, and mechanism of drug release also were studied. 5-fluorouracil (5FU) was found to be released in a controlled manner from the nanoparticles at pH = 4.8 (representing the cancerous cellular environment) and pH = 7.4 (representing the blood environment), governed by pseudo-second-order kinetics. The cytotoxicity study revealed that the anticancer delivery system of FPVA-FU-MLDH nanoparticles showed much better anticancer activity than the free drug, 5FU, against liver cancer and HepG2 cells, and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells.
Fulltext Synthesis and properties of magnetic nanotheranostics coated with polyethylene glycol/5-fluorouracil/layered double hydroxide

Ebadi M, Saifullah B, Buskaran K, Hussein MZ, Fakurazi S

Int J Nanomedicine, 2019;14:6661-6678.
PMID: 31695362 DOI: 10.2147/IJN.S214923

Background: Cancer treatments are being continually developed. Increasingly more effective and better-targeted treatments are available. As treatment has developed, the outcomes have improved.
Purpose: In this work, polyethylene glycol (PEG), layered double hydroxide (LDH) and 5-fluorouracil (5-FU) were used as a stabilizing agent, a carrier and an anticancer active agent, respectively.
Characterization and methods: Magnetite nanoparticles (Fe3O4) coated with polyethylene glycol (PEG) and co-coated with 5-fluorouracil/Mg/Al- or Zn/Al-layered double hydroxide were synthesized by co-precipitation technique. Structural, magnetic properties, particle shape, particle size and drug loading percentage of the magnetic nanoparticles were investigated by XRD, TGA, FTIR, DLS, FESEM, TEM, VSM, UV-vis spectroscopy and HPLC techniques.
Results: XRD, TGA and FTIR studies confirmed the formation of Fe3O4 phase and the presence of iron oxide nanoparticles, polyethylene glycol, LDH and the drug for all the synthesized samples. The size of the nanoparticles co-coated with Mg/Al-LDH is about 27 nm compared to 40 nm when they were co-coated with Zn/Al-LDH, with both showings near uniform spherical shape. The iron oxide nanoparticles retain their superparamagnetic property when they were coated with polyethylene glycol, polyethylene glycol co-coated with Mg/Al-LDH and polyethylene glycol co-coated with Zn/Al-LDH with magnetic saturation value of 56, 40 and 27 emu/g, respectively. The cytotoxicity study reveals that the anticancer nanodelivery system has better anticancer activity than the free drug, 5-FU against liver cancer HepG2 cells and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells.
Conclusion: These are unique core-shell nanoparticles synthesized with the presence of multiple functionalities are hoped can be used as a multifunctional nanocarrier with the capability of targeted delivery using an external magnetic field and can also be exploited as hypothermia for cancer cells in addition to the chemotherapy property.
Fulltext Development of a biocompatible nanodelivery system for tuberculosis drugs based on isoniazid-Mg/Al layered double hydroxide

Saifullah B, Arulselvan P, El Zowalaty ME, Fakurazi S, Webster TJ, Geilich BM, et al.

Int J Nanomedicine, 2014;9:4749-62.
PMID: 25336952 DOI: 10.2147/IJN.S63608

The primary challenge in finding a treatment for tuberculosis (TB) is patient non-compliance to treatment due to long treatment duration, high dosing frequency, and adverse effects of anti-TB drugs. This study reports on the development of a nanodelivery system that intercalates the anti-TB drug isoniazid into Mg/Al layered double hydroxides (LDHs). Isoniazid was found to be released in a sustained manner from the novel nanodelivery system in humans in simulated phosphate buffer solutions at pH 4.8 and pH 7.4. The nanodelivery formulation was highly biocompatible compared to free isoniazid against human normal lung and 3T3 mouse fibroblast cells. The formulation was active against Mycobacterium tuberculosis and gram-positive bacteria and gram-negative bacteria. Thus results show significant promise for the further study of these nanocomposites for the treatment of TB.
Fulltext Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

Saifullah B, El Zowalaty ME, Arulselvan P, Fakurazi S, Webster TJ, Geilich BM, et al.

Drug Des Devel Ther, 2014;8:1029-36.
PMID: 25114509 DOI: 10.2147/DDDT.S63753

The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis.
Fulltext Development of a highly biocompatible antituberculosis nanodelivery formulation based on para-aminosalicylic acid-zinc layered hydroxide nanocomposites

Saifullah B, Arulselvan P, El Zowalaty ME, Fakurazi S, Webster TJ, Geilich B, et al.

ScientificWorldJournal, 2014;2014:401460.
PMID: 25050392 DOI: 10.1155/2014/401460

Tuberculosis is a lethal epidemic, difficult to control disease, claiming thousands of lives every year. We have developed a nanodelivery formulation based on para-aminosalicylic acid (PAS) and zinc layered hydroxide using zinc nitrate salt as a precursor. The developed formulation has a fourfold higher efficacy of PAS against mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) found to be at 1.40 μg/mL compared to the free drug PAS with a MIC of 5.0 μg/mL. The newly developed formulation was also found active against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans. The formulation was also found to be biocompatible with human normal lung cells MRC-5 and mouse fibroblast cells-3T3. The in vitro release of PAS from the formulation was found to be sustained in a human body simulated phosphate buffer saline (PBS) solution at pH values of 7.4 and 4.8. Most importantly the nanocomposite prepared using zinc nitrate salt was advantageous in terms of yield and free from toxic zinc oxide contamination and had higher biocompatibility compared to one prepared using a zinc oxide precursor. In summary, these promising in vitro results are highly encouraging for the continued investigation of para-aminosalicylic acid and zinc layered hydroxide nanocomposites in vivo and eventual preclinical studies.
Fulltext Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate-zinc aluminum-layered double-hydroxide nanocomposites

Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S

Drug Des Devel Ther, 2013;7:1365-75.
PMID: 24255593 DOI: 10.2147/DDDT.S50665

We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours.
Fulltext Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

Saifullah B, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S

Chem Cent J, 2013;7(1):72.
PMID: 23601852 DOI: 10.1186/1752-153X-7-72

Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.
Fulltext Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites

Saifullah B, El Zowalaty ME, Arulselvan P, Fakurazi S, Webster TJ, Geilich BM, et al.

Int J Nanomedicine, 2016;11:3225-37.
PMID: 27486322 DOI: 10.2147/IJN.S102406

The chemotherapy for tuberculosis (TB) is complicated by its long-term treatment, its frequent drug dosing, and the adverse effects of anti-TB drugs. In this study, we have developed two nanocomposites (A and B) by intercalating the anti-TB drug isoniazid (INH) into Zn/Al-layered double hydroxides. The average size of the nanocomposites was found to bê164 nm. The efficacy of the Zn/Al-layered double hydroxides intercalated INH against Mycobacterium tuberculosis was increased by approximately three times more than free INH. The nanocomposites were also found to be active against Gram-positive and -negative bacteria. Compared to the free INH, the nanodelivery formulation was determined to be three times more biocompatible with human normal lung fibroblast MRC-5 cells and 3T3 fibroblast cells at a very high concentration of 50 µg/mL for up to 72 hours. The in vitro release of INH from the Zn/Al-layered double hydroxides was found to be sustained in human body-simulated buffer solutions of pH 4.8 and 7.4. This research is a step forward in making the TB chemotherapy patient friendly.
Corrigendum to "Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid" [J. Mater. Sci. Eng. C 74(2017) 177-185]

Barahuie F, Saifullah B, Dorniani D, Fakurazi S, Karthivashan G, Hussein MZ, et al.

Mater Sci Eng C Mater Biol Appl, 2017 06 01;75:1525.
PMID: 28415446 DOI: 10.1016/j.msec.2017.03.050
Fulltext Incorporation of Levodopa into Biopolymer Coatings Based on Carboxylated Carbon Nanotubes for pH-Dependent Sustained Release Drug Delivery

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.
Fulltext Graphene Oxide⁻PEG⁻Protocatechuic Acid Nanocomposite Formulation with Improved Anticancer Properties

Saifullah B, Buskaran K, Shaikh RB, Barahuie F, Fakurazi S, Mohd Moklas MA, et al.

Nanomaterials (Basel), 2018 Oct 11;8(10).
PMID: 30314340 DOI: 10.3390/nano8100820

The treatment of cancer through chemotherapy is limited by its toxicity to healthy tissues and organs, and its inability to target the cancer site. In this study, we have designed an anticancer nanocomposite delivery system for protocatechuic acid (PCA) using graphene oxide⁻polyethylene glycol as the nanocarrier, and coated with folic acid (GO⁻PEG⁻PCA⁻FA) for targeting the cancer cells. The designed anticancer delivery system was found to show much better anticancer activity than the free drug PCA against liver cancer HEP-G2 cells and human colon cancer HT-29 cells; at same time, it was found to be less toxic to normal fibroblast 3T3 cells. The folate-coated anticancer delivery system was found to show better activity then the free drug and the uncoated anticancer delivery system. The in vitro release of the PCA was found to be sustained in human physiological pHs, i.e., blood pH 7.4 and intracellular lysosomal pH 4.8. These in vitro findings are highly encouraging for further in vivo evaluation studies.
Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe₃O₄-PEG-GA) Against Lung, Breast and Colon Cancer Cells

Rosman R, Saifullah B, Maniam S, Dorniani D, Hussein MZ, Fakurazi S

Nanomaterials (Basel), 2018 Feb 02;8(2).
PMID: 29393902 DOI: 10.3390/nano8020083

Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe₃O₄-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe₃O₄-PEG) nanocarrier and of anticancer nanocomposite (Fe₃O₄-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe₃O₄-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.
Synthesis of (Hexaconazole-Zinc/Aluminum-Layered Double Hydroxide Nanocomposite) Fungicide Nanodelivery System for Controlling Ganoderma Disease in Oil Palm

Mustafa IF, Hussein MZ, Saifullah B, Idris AS, Hilmi NHZ, Fakurazi S

J Agric Food Chem, 2018 Jan 31;66(4):806-813.
PMID: 29281878 DOI: 10.1021/acs.jafc.7b04222

A fungicide, hexaconazole was successfully intercalated into the intergalleries of zinc/aluminum-layered double hydroxide (ZALDH) using the ion-exchange method. Due to the intercalation of hexaconazole, the basal spacing of the ZALDH was increased from 8.7 Å in ZALDH to 29.4 Å in hexaconazole-intercalated ZALDH (HZALDH). The intercalation of hexaconazole into the interlayer of the nanocomposite was confirmed using the Fourier-transform infrared (FTIR) study. This supramolecular chemistry intercalation process enhanced the thermal stability of the hexaconazole moiety. The fungicide loading was estimated to be 51.8%. The nanodelivery system also shows better inhibition toward the Ganoderma boninense growth than the counterpart, free hexaconazole. The results from this work have a great potential to be further explored for combating basal stem rot (BSR) disease in oil palm plantation.
Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid

Barahuie F, Saifullah B, Dorniani D, Fakurazi S, Karthivashan G, Hussein MZ, et al.

Mater Sci Eng C Mater Biol Appl, 2017 May 01;74:177-185.
PMID: 28254283 DOI: 10.1016/j.msec.2016.11.114

We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV-vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π-π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV-vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of >80% even at higher concentration of 50μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form.
Fulltext Nano-Formulation of Ethambutol with Multifunctional Graphene Oxide and Magnetic Nanoparticles Retains Its Anti-Tubercular Activity with Prospects of Improving Chemotherapeutic Efficacy

Saifullah B, Maitra A, Chrzastek A, Naeemullah B, Fakurazi S, Bhakta S, et al.

Molecules, 2017 Oct 12;22(10).
PMID: 29023384 DOI: 10.3390/molecules22101697

Tuberculosis (TB) is a dreadful bacterial disease, infecting millions of human and cattle every year worldwide. More than 50 years after its discovery, ethambutol continues to be an effective part of the World Health Organization's recommended frontline chemotherapy against TB. However, the lengthy treatment regimens consisting of a cocktail of antibiotics affect patient compliance. There is an urgent need to improve the current therapy so as to reduce treatment duration and dosing frequency. In this study, we have designed a novel anti-TB multifunctional formulation by fabricating graphene oxide with iron oxide magnetite nanoparticles serving as a nano-carrier on to which ethambutol was successfully loaded. The designed nanoformulation was characterised using various analytical techniques. The release of ethambutol from anti-TB multifunctional nanoparticles formulation was found to be sustained over a significantly longer period of time in phosphate buffer saline solution at two physiological pH (7.4 and 4.8). Furthermore, the nano-formulation showed potent anti-tubercular activity while remaining non-toxic to the eukaryotic cells tested. The results of this in vitro evaluation of the newly designed nano-formulation endorse its further development in vivo.
Fulltext Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system

Barahuie F, Dorniani D, Saifullah B, Gothai S, Hussein MZ, Pandurangan AK, et al.

Int J Nanomedicine, 2017;12:2361-2372.
PMID: 28392693 DOI: 10.2147/IJN.S126245

Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell.

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