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Displaying publications 101 - 120 of 182 in total

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Fulltext Multifaceted prospects of nanocomposites for cardiovascular grafts and stents

Vellayappan MV, Balaji A, Subramanian AP, John AA, Jaganathan SK, Murugesan S, et al.

Int J Nanomedicine, 2015;10:2785-803.
PMID: 25897223 DOI: 10.2147/IJN.S80121

Cardiovascular disease is the leading cause of death across the globe. The use of synthetic materials is indispensable in the treatment of cardiovascular disease. Major drawbacks related to the use of biomaterials are their mechanical properties and biocompatibility, and these have to be circumvented before promoting the material to the market or clinical setting. Revolutionary advancements in nanotechnology have introduced a novel class of materials called nanocomposites which have superior properties for biomedical applications. Recently, there has been a widespread recognition of the nanocomposites utilizing polyhedral oligomeric silsesquioxane, bacterial cellulose, silk fibroin, iron oxide magnetic nanoparticles, and carbon nanotubes in cardiovascular grafts and stents. The unique characteristics of these nanocomposites have led to the development of a wide range of nanostructured copolymers with appreciably enhanced properties, such as improved mechanical, chemical, and physical characteristics suitable for cardiovascular implants. The incorporation of advanced nanocomposite materials in cardiovascular grafts and stents improves hemocompatibility, enhances antithrombogenicity, improves mechanical and surface properties, and decreases the microbial response to the cardiovascular implants. A thorough attempt is made to summarize the various applications of nanocomposites for cardiovascular graft and stent applications. This review will highlight the recent advances in nanocomposites and also address the need of future research in promoting nanocomposites as plausible candidates in a campaign against cardiovascular disease.
Fulltext Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

Yong CY, Yeap SK, Ho KL, Omar AR, Tan WS

Int J Nanomedicine, 2015;10:2751-63.
PMID: 25897220 DOI: 10.2147/IJN.S77405

Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii. The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future.
Fulltext Colorimetric biosensing of targeted gene sequence using dual nanoparticle platforms

Thavanathan J, Huang NM, Thong KL

Int J Nanomedicine, 2015;10:2711-22.
PMID: 25897217 DOI: 10.2147/IJN.S74753

We have developed a colorimetric biosensor using a dual platform of gold nanoparticles and graphene oxide sheets for the detection of Salmonella enterica. The presence of the invA gene in S. enterica causes a change in color of the biosensor from its original pinkish-red to a light purplish solution. This occurs through the aggregation of the primary gold nanoparticles-conjugated DNA probe onto the surface of the secondary graphene oxide-conjugated DNA probe through DNA hybridization with the targeted DNA sequence. Spectrophotometry analysis showed a shift in wavelength from 525 nm to 600 nm with 1 μM of DNA target. Specificity testing revealed that the biosensor was able to detect various serovars of the S. enterica while no color change was observed with the other bacterial species. Sensitivity testing revealed the limit of detection was at 1 nM of DNA target. This proves the effectiveness of the biosensor in the detection of S. enterica through DNA hybridization.
Fulltext Hydroxypropylcellulose as a novel green reservoir for the synthesis, stabilization, and storage of silver nanoparticles

Hussain MA, Shah A, Jantan I, Shah MR, Tahir MN, Ahmad R, et al.

Int J Nanomedicine, 2015;10:2079-88.
PMID: 25844038 DOI: 10.2147/IJN.S75874

Polysaccharides are attracting the vigil eye of researchers in order to design the green synthesis of silver nanoparticles (Ag NPs) of diverse size, shape, and application. We report an environmentally friendly method to synthesize Ag NPs where no physical reaction conditions were employed. Hydroxypropylcellulose (HPC) was used as a template nanoreactor, stabilizer, and capping agent to obtain Ag NPs. Different concentrations of AgNO3 solutions (50 mmol, 75 mmol, and 100 mmol) were mixed with a concentrated aqueous solution of HPC and the progress of the reaction was monitored by noting color changes of the reaction mixture at different reaction times for up to 24 hours. Characteristic ultraviolet-visible spectroscopy (UV/Vis) absorption bands of Ag NPs were observed in the range of 388-452 nm. The morphology of the Ag NPs was studied by scanning electron microscopy, transmission electron microscopy (TEM), and atomic force microscopy. The TEM images confirmed that the size of the Ag NPs was in the range of 25-55 nm. Powder X-ray diffraction studies showed that the crystal phase of the Ag NPs was face-centered cubic. The as-prepared Ag NPs were found to be stable, and no changes in size and morphology were observed after storage in HPC thin films over 1 year, as indicated by UV/Vis spectra. So, the present work furnishes a green and economical strategy for the synthesis and storage of stable Ag NPs. As-synthesized Ag NPs showed significant antimicrobial activity against different bacterial (Escherichia coli, Staphylococcus epidermidis, S. aureus, Bacillus subtilis, Pseudomonas aeruginosa) and fungal strains (Actinomycetes and Aspergillus niger).
Fulltext Exceedingly biocompatible and thin-layered reduced graphene oxide nanosheets using an eco-friendly mushroom extract strategy

Muthoosamy K, Bai RG, Abubakar IB, Sudheer SM, Lim HN, Loh HS, et al.

Int J Nanomedicine, 2015;10:1505-19.
PMID: 25759577 DOI: 10.2147/IJN.S75213

PURPOSE: A simple, one-pot strategy was used to synthesize reduced graphene oxide (RGO) nanosheets by utilizing an easily available over-the-counter medicinal and edible mushroom, Ganoderma lucidum.
METHODS: The mushroom was boiled in hot water to liberate the polysaccharides, the extract of which was then used directly for the reduction of graphene oxide. The abundance of polysaccharides present in the mushroom serves as a good reducing agent. The proposed strategy evades the use of harmful and expensive chemicals and avoids the typical tedious reaction methods.
RESULTS: More importantly, the mushroom extract can be easily separated from the product without generating any residual byproducts and can be reused at least three times with good conversion efficiency (75%). It was readily dispersible in water without the need of ultrasonication or any surfactants; whereas 5 minutes of ultrasonication with various solvents produced RGO which was stable for the tested period of 1 year. Based on electrochemical measurements, the followed method did not jeopardize RGO's electrical conductivity. Moreover, the obtained RGO was highly biocompatible to not only colon (HT-29) and brain (U87MG) cancer cells, but was also viable towards normal cells (MRC-5).
CONCLUSION: Besides being eco-friendly, this mushroom based approach is easily scalable and demonstrates remarkable RGO stability and biocompatibility, even without any form of functionalization.
Fulltext Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

Butt AM, Mohd Amin MC, Katas H

Int J Nanomedicine, 2015;10:1321-34.
PMID: 25709451 DOI: 10.2147/IJN.S78438

BACKGROUND: Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells.
METHODS: FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue(®) assay.
RESULTS: The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX-DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX.
CONCLUSION: FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake.
Fulltext Microwave-assisted fibrous decoration of mPE surface utilizing Aloe vera extract for tissue engineering applications

Balaji A, Jaganathan SK, Supriyanto E, Muhamad II, Khudzari AZ

Int J Nanomedicine, 2015;10:5909-23.
PMID: 26425089 DOI: 10.2147/IJN.S84307

Developing multifaceted, biocompatible, artificial implants for tissue engineering is a growing field of research. In recent times, several works have been reported about the utilization of biomolecules in combination with synthetic materials to achieve this process. Accordingly, in this study, the ability of an extract obtained from Aloe vera, a commonly used medicinal plant in influencing the biocompatibility of artificial material, is scrutinized using metallocene polyethylene (mPE). The process of coating dense fibrous Aloe vera extract on the surface of mPE was carried out using microwaves. Then, several physicochemical and blood compatibility characterization experiments were performed to disclose the effects of corresponding surface modification. The Fourier transform infrared spectrum showed characteristic vibrations of several active constituents available in Aloe vera and exhibited peak shifts at far infrared regions due to aloe-based mineral deposition. Meanwhile, the contact angle analysis demonstrated a drastic increase in wettability of coated samples, which confirmed the presence of active components on glazed mPE surface. Moreover, the bio-mimic structure of Aloe vera fibers and the influence of microwaves in enhancing the coating characteristics were also meticulously displayed through scanning electron microscopy micrographs and Hirox 3D images. The existence of nanoscale roughness was interpreted through high-resolution profiles obtained from atomic force microscopy. And the extent of variations in irregularities was delineated by measuring average roughness. Aloe vera-induced enrichment in the hemocompatible properties of mPE was established by carrying out in vitro tests such as activated partial thromboplastin time, prothrombin time, platelet adhesion, and hemolysis assay. In conclusion, the Aloe vera-glazed mPE substrate was inferred to attain desirable properties required for multifaceted biomedical implants.
Fulltext Cytotoxicity and physicochemical characterization of iron-manganese-doped sulfated zirconia nanoparticles

Al-Fahdawi MQ, Rasedee A, Al-Qubaisi MS, Alhassan FH, Rosli R, El Zowalaty ME, et al.

Int J Nanomedicine, 2015;10:5739-50.
PMID: 26425082 DOI: 10.2147/IJN.S82586

Iron-manganese-doped sulfated zirconia nanoparticles with both Lewis and Brønsted acidic sites were prepared by a hydrothermal impregnation method followed by calcination at 650°C for 5 hours, and their cytotoxicity properties against cancer cell lines were determined. The characterization was carried out using X-ray diffraction, thermogravimetric analysis, Fourier transform infrared spectroscopy, Brauner-Emmett-Teller (BET) surface area measurements, X-ray fluorescence, X-ray photoelectron spectroscopy, zeta size potential, and transmission electron microscopy (TEM). The cytotoxicity of iron-manganese-doped sulfated zirconia nanoparticles was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays against three human cancer cell lines (breast cancer MDA-MB231 cells, colon carcinoma HT29 cells, and hepatocellular carcinoma HepG2 cells) and two normal human cell lines (normal hepatocyte Chang cells and normal human umbilical vein endothelial cells [HUVECs]). The results suggest for the first time that iron-manganese-doped sulfated zirconia nanoparticles are cytotoxic to MDA-MB231 and HepG2 cancer cells but have less toxicity to HT29 and normal cells at concentrations from 7.8 μg/mL to 500 μg/mL. The morphology of the treated cells was also studied, and the results supported those from the cytotoxicity study in that the nanoparticle-treated HepG2 and MDA-MB231 cells had more dramatic changes in cell morphology than the HT29 cells. In this manner, this study provides the first evidence that iron-manganese-doped sulfated zirconia nanoparticles should be further studied for a wide range of cancer applications without detrimental effects on healthy cell functions.
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 Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

Roy P, Das S, Auddy RG, Mukherjee A

Int J Nanomedicine, 2014;9:4723-35.
PMID: 25336950 DOI: 10.2147/IJN.S65262

Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7 ± 17.17 nm and ζ-potential +34.4 ± 1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery.
Fulltext Downregulation of immunological mediators in 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions by hydrocortisone-loaded chitosan nanoparticles

Hussain Z, Katas H, Mohd Amin MC, Kumolosasi E, Sahudin S

Int J Nanomedicine, 2014;9:5143-56.
PMID: 25395851 DOI: 10.2147/IJN.S71543

Atopic dermatitis is a chronic, noncontiguous, and exudative disorder accompanied by perivascular infiltration of immune mediators, including T-helper (Type 1 helper/Type 2 helper) cells, mast cells, and immunoglobulin E. The current study explores the immunomodulatory and histological effects of nanoparticle (NP)-based transcutaneous delivery of hydrocortisone (HC).
Fulltext Proliferation and stemness preservation of human adipose-derived stem cells by surface-modified in situ TiO₂ nanofibrous surfaces

Tan AW, Tay L, Chua KH, Ahmad R, Akbar SA, Pingguan-Murphy B

Int J Nanomedicine, 2014;9:5389-401.
PMID: 25473278 DOI: 10.2147/IJN.S72659

Two important criteria of an ideal biomaterial in the field of stem cells research are to regulate the cell proliferation without the loss of its pluripotency and to direct the differentiation into a specific cell lineage when desired. The present study describes the influence of TiO2 nanofibrous surface structures on the regulation of proliferation and stemness preservation of adipose-derived stem cells (ADSCs). TiO2 nanofiber arrays were produced in situ onto Ti-6Al-4V substrate via a thermal oxidation process and the successful fabrication of these nanostructures was confirmed by field emission scanning electron microscopy (FESEM), energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and contact angle measurement. ADSCs were seeded on two types of Ti-6Al-4V surfaces (TiO2 nanofibers and flat control), and their morphology, proliferation, and stemness expression were analyzed using FESEM, AlamarBlue assay, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) after 2 weeks of incubation, respectively. The results show that ADSCs exhibit better adhesion and significantly enhanced proliferation on the TiO2 nanofibrous surfaces compared to the flat control surfaces. The greater proliferation ability of TiO2 nanofibrous surfaces was further confirmed by the results of cell cycle assay. More importantly, TiO2 nanofibrous surfaces significantly upregulate the expressions of stemness markers Sox-2, Nanog3, Rex-1, and Nestin. These results demonstrate that TiO2 nanofibrous surfaces can be used to enhance cell adhesion and proliferation while simultaneously maintaining the stemness of ADSCs, thereby representing a promising approach for their potential application in the field of bone tissue engineering as well as regenerative therapies.
Fulltext Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application

Mahmood S, Taher M, Mandal UK

Int J Nanomedicine, 2014;9:4331-46.
PMID: 25246789 DOI: 10.2147/IJN.S65408

Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon(®) 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm(2)/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride-loaded transfersome formulation could be a superior alternative to oral delivery of the drug.
Fulltext Comparison of process parameter optimization using different designs in nanoemulsion-based formulation for transdermal delivery of fullerene

Ngan CL, Basri M, Lye FF, Fard Masoumi HR, Tripathy M, Karjiban RA, et al.

Int J Nanomedicine, 2014;9:4375-86.
PMID: 25258528 DOI: 10.2147/IJN.S65689

This research aims to formulate and to optimize a nanoemulsion-based formulation containing fullerene, an antioxidant, stabilized by a low amount of mixed surfactants using high shear and the ultrasonic emulsification method for transdermal delivery. Process parameters optimization of fullerene nanoemulsions was done by employing response surface methodology, which involved statistical multivariate analysis. Optimization of independent variables was investigated using experimental design based on Box-Behnken design and central composite rotatable design. An investigation on the effect of the homogenization rate (4,000-5,000 rpm), sonication amplitude (20%-60%), and sonication time (30-150 seconds) on the particle size, ζ-potential, and viscosity of the colloidal systems was conducted. Under the optimum conditions, the central composite rotatable design model suggested the response variables for particle size, ζ-potential, and viscosity of the fullerene nanoemulsion were 152.5 nm, -52.6 mV, and 44.6 pascal seconds, respectively. In contrast, the Box-Behnken design model proposed that preparation under the optimum condition would produce nanoemulsion with particle size, ζ-potential, and viscosity of 148.5 nm, -55.2 mV, and 39.9 pascal seconds, respectively. The suggested process parameters to obtain optimum formulation by both models yielded actual response values similar to the predicted values with residual standard error of <2%. The optimum formulation showed more elastic and solid-like characteristics due to the existence of a large linear viscoelastic region.
Fulltext Synthesis, characterization, and antimicrobial activity of an ampicillin-conjugated magnetic nanoantibiotic for medical applications

Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Geilich BM, Webster TJ

Int J Nanomedicine, 2014;9:3801-14.
PMID: 25143729 DOI: 10.2147/IJN.S61143

Because of their magnetic properties, magnetic nanoparticles (MNPs) have numerous diverse biomedical applications. In addition, because of their ability to penetrate bacteria and biofilms, nanoantimicrobial agents have become increasingly popular for the control of infectious diseases. Here, MNPs were prepared through an iron salt coprecipitation method in an alkaline medium, followed by a chitosan coating step (CS-coated MNPs); finally, the MNPs were loaded with ampicillin (amp) to form an amp-CS-MNP nanocomposite. Both the MNPs and amp-CS-MNPs were subsequently characterized and evaluated for their antibacterial activity. X-ray diffraction results showed that the MNPs and nanocomposites were composed of pure magnetite. Fourier transform infrared spectra and thermogravimetric data for the MNPs, CS-coated MNPs, and amp-CS-MNP nanocomposite were compared, which confirmed the CS coating on the MNPs and the amp-loaded nanocomposite. Magnetization curves showed that both the MNPs and the amp-CS-MNP nanocomposites were superparamagnetic, with saturation magnetizations at 80.1 and 26.6 emu g(-1), respectively. Amp was loaded at 8.3%. Drug release was also studied, and the total release equilibrium for amp from the amp-CS-MNPs was 100% over 400 minutes. In addition, the antimicrobial activity of the amp-CS-MNP nanocomposite was determined using agar diffusion and growth inhibition assays against Gram-positive bacteria and Gram-negative bacteria, as well as Candida albicans. The minimum inhibitory concentration of the amp-CS-MNP nanocomposite was determined against bacteria including Mycobacterium tuberculosis. The synthesized nanocomposites exhibited antibacterial and antifungal properties, as well as antimycobacterial effects. Thus, this study introduces a novel β-lactam antibacterial-based nanocomposite that can decrease fungus activity on demand for numerous medical applications.
Fulltext Characterization of rice bran wax policosanol and its nanoemulsion formulation

Ishaka A, Umar Imam M, Mahamud R, Zuki AB, Maznah I

Int J Nanomedicine, 2014;9:2261-9.
PMID: 24872689 DOI: 10.2147/IJN.S56999

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects; however, it has a bioavailability of less than 10%. Therefore, there is a need to improve its bioavailability, and one of the ways of doing this is by nanoemulsion formulation. Different droplet size distributions are usually achieved when emulsions are formed, which solely depends on the preparation method used. Mostly, emulsions are intended for better delivery with maintenance of the characteristics and properties of the leading components. In this study, policosanol was extracted from rice bran wax, its composition was determined by gas chromatography mass spectrophotometry, nanoemulsion was made, and the physical stability characteristics were determined. The results showed that policosanol nanoemulsion has a nanosize particle distribution below 100 nm (92.56-94.52 nm), with optimum charge distribution (-55.8 to -45.12 mV), pH (6.79-6.92) and refractive index (1.50); these were monitored and found to be stable for 8 weeks. The stability of policosanol nanoemulsion confers the potential to withstand long storage times.
Fulltext Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams

Rahman WN, Corde S, Yagi N, Abdul Aziz SA, Annabell N, Geso M

Int J Nanomedicine, 2014;9:2459-67.
PMID: 24899803 DOI: 10.2147/IJN.S59471

Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects of gold nanoparticles with ionizing radiation.
Fulltext Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

Lim WM, Rajinikanth PS, Mallikarjun C, Kang YB

Int J Nanomedicine, 2014;9:2117-26.
PMID: 24833900 DOI: 10.2147/IJN.S57565

The objectives of this study were to develop and characterize itraconazole (ITZ)-loaded nanostructured lipid carriers (NLCs) and to study their potential for drug delivery into the brain. Precirol(®) ATO 5 and Transcutol(®) HP were selected as the lipid phase, and Tween(®) 80 and Solutol(®) HS15 as surfactants. The ITZ-NLCs were prepared by a hot and high-pressure homogenization method. The entrapment efficiency for the best formulation batch was analyzed using high-performance liquid chromatography and was found to be 70.5%±0.6%. The average size, zeta potential, and polydispersity index for the ITZ-NLCs used for animal studies were found to be 313.7±15.3 nm, -18.7±0.30 mV, and 0.562±0.070, respectively. Transmission electron microscopy confirmed that ITZ-NLCs were spherical in shape, with a size of less than 200 nm. Differential scanning calorimetry and X-ray diffractometry analysis showed that ITZ was encapsulated in the lipid matrix and present in the amorphous form. The in vitro release study showed that ITZ-NLCs achieved a sustained release, with cumulative release of 80.6%±5.3% up to 24 hours. An in vivo study showed that ITZ-NLCs could increase the ITZ concentration in the brain by almost twofold. These results suggest that ITZ-NLCs can be exploited as nanocarriers to achieve sustained release and brain-targeted delivery.
Fulltext Cytotoxic effect of magnetic iron oxide nanoparticles synthesized via seaweed aqueous extract

Namvar F, Rahman HS, Mohamad R, Baharara J, Mahdavi M, Amini E, et al.

Int J Nanomedicine, 2014;9:2479-88.
PMID: 24899805 DOI: 10.2147/IJN.S59661

Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 μg/mL (HepG2), 18.75±2.1 μg/mL (MCF-7), 12.5±1.7 μg/mL (HeLa), and 6.4±2.3 μg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.
Fulltext Zerumbone-loaded nanostructured lipid carrier induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in a human lymphoblastic leukemia cell line

Rahman HS, Rasedee A, Abdul AB, Zeenathul NA, Othman HH, Yeap SK, et al.

Int J Nanomedicine, 2014;9:527-38.
PMID: 24549090 DOI: 10.2147/IJN.S54346

This investigation evaluated the antileukemia properties of a zerumbone (ZER)-loaded nanostructured lipid carrier (NLC) prepared by hot high-pressure homogenization techniques in an acute human lymphoblastic leukemia (Jurkat) cell line in vitro. The apoptogenic effect of the ZER-NLC on Jurkat cells was determined by fluorescent and electron microscopy, Annexin V-fluorescein isothiocyanate, Tdt-mediated dUTP nick-end labeling assay, cell cycle analysis, and caspase activity. An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay showed that ZER-NLC did not have adverse effects on normal human peripheral blood mononuclear cells. ZER-NLC arrested the Jurkat cells at G2/M phase with inactivation of cyclin B1 protein. The study also showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the intrinsic apoptotic pathway via activation of caspase-3 and caspase-9, release of cytochrome c from the mitochondria into the cytosol, and subsequent cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP). These findings show that the ZER-NLC is a potentially useful treatment for acute lymphoblastic leukemia in humans.

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