Modeling and optimization of nanoemulsion containing Sorafenib for cancer treatment by response surface methodology

The aim of this study is the development of nanoemulsions for intravenous administration of Sorafenib, which is a poorly soluble drug with no parenteral treatment. The formulation was prepared by a high energy emulsification method and optimized by response surface methodology. The effects of overhead stirring time, high shear rate, high shear time, and cycles of high-pressure homogenizer were studied in the preparation of nanoemulsion loaded with Sorafenib. Most of the particles in nanoemulsion are spherical in shape, the smallest particle size being 82.14nm. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a tetrazole reveal that the optimum formulation does not affect normal cells significantly in low drug concentrations but could remove the cancer cells. Finally, a formulation containing Sorafenib retained its properties over a period of 90days. With characterization, the study of the formulated nanoemulsion has the potential to be used as a parenteral nanoemulsion in the treatment of cancer. Graphical abstract Schematic figure of high pressure homogenizer device

Enhancement of encapsulation efficiency of nanoemulsion-containing aripiprazole for the treatment of schizophrenia using mixture experimental design

Hamid Reza Fard Masoumi, Mahiran Basri, Wan Sarah Samiun, Zahra Izadiyan, Chaw Jiang Lim Nanodelivery Group, Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Aripiprazole is considered as a third-generation antipsychotic drug with excellent therapeutic efficacy in controlling schizophrenia symptoms and was the first atypical anti­psychotic agent to be approved by the US Food and Drug Administration. Formulation of nanoemulsion-containing aripiprazole was carried out using high shear and high pressure homo­genizers. Mixture experimental design was selected to optimize the composition of nanoemulsion. A very small droplet size of emulsion can provide an effective encapsulation for delivery system in the body. The effects of palm kernel oil ester (3–6 wt%), lecithin (2–3 wt%), Tween 80 (0.5–1 wt%), glycerol (1.5–3 wt%), and water (87–93 wt%) on the droplet size of aripiprazole nanoemulsions were investigated. The mathematical model showed that the optimum formulation for preparation of aripiprazole nanoemulsion having the desirable criteria was 3.00% of palm kernel oil ester, 2.00% of lecithin, 1.00% of Tween 80, 2.25% of glycerol, and 91.75% of water. Under optimum formulation, the corresponding predicted response value for droplet size was 64.24 nm, which showed an excellent agreement with the actual value (62.23 nm) with residual standard error <3.2%. Keywords: schizoaffective disorder, antipsychotic drug, bipolar I disorder, D-optimal mixture design, optimization formulatio

Evaluation of heavy metals removal by cross-linked (polyvinyl alcohol/ chitosan/magnetic) nano fibrous membrane prepared by electro spinning technique

In this study, chitosan/polyvinyl alcohol (PVA)/magnetic nano fibrous membrane was fabricated via electro spinning. First, magnetic nano particles with average size of 7.98 nm, were fabricated using co-precipitation method. Then, chitosan solution was blended with aqueous PVA solution in different weight ratios. The electro spun fibers were kept in a glass desiccator saturated with (50% aqueous solution) of glutaraldehyde vapor for 24 h. Morphological analysis of chitosan/PVA electro spun nano fibrous showed a defect-free nano fiber material with 50:50 weight ratio of chitosan/PVA. Subsequently, 1 wt.% of magnetic nano particles was added to 50:50 chitosan/PVA solution and then, fine bead free nano fibrous electro spun was fabricated. The resulting nano fiber was characterized with field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-Ray diffraction, Fourier transform infrared spectroscopy, swelling test, and adsorption test. The resulting membrane was stable in distilled water, acidic, and basic media overnight. Moreover, the adsorption ability of nano fibrous membrane was studied over Cr6+, Pb2+, and Ni2+ ions. Kinetic parameters were estimated using the first-order and pseudo-second-order models. Kinetic study showed that adsorption rate was high. Therefore, chitosan/polyvinyl alcohol (PVA)/magnetic nano fibrous membrane can be a useful material for water treatment at moderate concentration of heavy metals

A review of small molecules and drug delivery applications using gold and iron nanoparticles

Hossein Jahangirian,1 Katayoon Kalantari,2 Zahra Izadiyan,3 Roshanak Rafiee-Moghaddam,1 Kamyar Shameli,3 Thomas J Webster1 1Department of Chemical Engineering, 313 Snell Engineering Center, Northeastern University, Boston, MA, USA; 2Centre of Advanced Materials (CAM), Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Environment and Green Technology, Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Kuala Lumpur, Malaysia Abstract: Conventional cancer treatment techniques show several limitations including low or no specificity and consequently a low efficacy in discriminating between cancer cells and healthy cells. Recent nanotechnology developments have introduced smart and novel therapeutic nanomaterials that take advantage of various targeting approaches. The use of nanotechnology in medicine and, more specifically, drug delivery is set to spread even more rapidly than it has over the past two decades. Currently, many nanoparticles (NPs) are under investigation for drug delivery including those for cancer therapy. Targeted nanomaterials bind selectively to cancer cells and greatly affect them with only a minor effect on healthy cells. Gold nanoparticles (Au-NPs), specifically, have been identified as significant candidates for new cancer therapeutic modalities because of their biocompatibility, easy functionalization and fabrication, optical tunable characteristics, and chemophysical stability. In the last decade, there has been significant research on Au-NPs and their biomedical applications. Functionalized Au-NPs represent highly attractive and promising candidates for drug delivery, owing to their unique dimensions, tunable surface functionalities, and controllable drug release. Further, iron oxide NPs due to their “superparamagnetic” properties have been studied and have demonstrated successful employment in numerous applications. In targeted drug delivery systems, drug-loaded iron oxide NPs can accumulate at the tumor site with the aid of an external magnetic field. This can lead to incremental effectiveness in drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order for the application of iron oxide NPs in the human body to be realized, they should be biodegradable and biocompatible to minimize toxicity. This review illustrates recent advances in the field drug and small molecule delivery such as fluorouracil, folic acid, doxorubicin, paclitaxel, and daunorubicin, specifically when using gold and iron oxide NPs as carriers of anticancer therapeutic agents. Keywords: small molecules, drug delivery, nanoparticles, gold nanoparticles, iron oxide nanoparticle

Anticancer activity of 5-fluorouracil-loaded nanoemulsions containing fe3o4/au core-shell nanoparticles

Nanoemulsions (NEs) as multi-compartmentalized systems are extensively considered as versatile drug delivery systems, due to their multifunctional and tuneable physicochemical properties. Here, water-in-oil-in-water (WOW) NEs were formulated using Juglans regia-based Fe3O4/Au-core-shell nanoparticles to encapsulate 5-Fluorouracil (5-FU) for potential colorectal cancer treatment. Response surface methodology, FTIR, TGA, TEM, DLS, VSM, UV-vis spectroscopy, and viscosity measurements were used to characterize the fabricated samples. The analysis confirmed the successful synthesis of Au, Fe3O4, and Fe3O4/Au core-shell nanoparticles with the Juglans regia (J. regia) extract as a green stabilizer and also reducing agent. The NE displayed a spherical-shape and TEM size of~30 nm. It also exhibited good colloidal stability and multifunctional features related to its components. TGA data indicated that 5-FU increased thermal stability after its loading into the nanoemulsion as a drug carrier. 5-FU release from the NE carrier presented a time-delayed behavior and higher release dosage in media at pH 4 compared to pH 7 within 48 h. When tested against colorectal-derived cell lines, 0.78 µg/mL of 5-FU-loaded Fe3O4/Au core-shell NEs showed potent anticancer activity against HCT116 cancerous cells, while exhibiting low toxicity towards CCD112 normal cells. In conclusion, the synthesized 5-FU-loaded NEs can be potently used as an anticancer drug carrier model, owing to its nano-scale size and other functionalities, which should be further studied

Ultrasmall superparamagnetic Fe3O4 nanoparticles: honey-based green and facile synthesis and in vitro viability assay

Elisa Rasouli,1 Wan Jeffrey Basirun,2 Majid Rezayi,3,4 Kamyar Shameli,5 Esmail Nourmohammadi,6 Roshanak Khandanlou,7 Zahra Izadiyan,5 Hoda Khoshdel Sarkarizi8 1Nanotechnology & Catalysis Research Centre, Institute of Postgraduate Studies, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 3Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 4Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 5Malaysia-Japan International Institute of Technology, University Technology Malaysia, Kuala Lumpur, Malaysia; 6Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 7School of Psychological and Clinical Sciences, Faculty of Engineering, Health, Science and the Environment, Charles Darwin University, Darwin, NT, Australia; 8Department of Anatomical Sciences and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Introduction: In the present research, we report a quick and green synthesis of magnetite nanoparticles (Fe3O4-NPs) in aqueous solution using ferric and ferrous chloride, with different percentages of natural honey (0.5%, 1.0%, 3.0% and 5.0% w/v) as the precursors, stabilizer, reducing and capping agent, respectively. The effect of the stabilizer on the magnetic properties and size of Fe3O4-NPs was also studied. Methods: The nanoparticles were characterized by X-ray diffraction (XRD) analysis, field emission scanning electron microscopy, energy dispersive X-ray fluorescence, transmission electron microscopy (TEM), vibrating sample magnetometry (VSM) and Fourier transform infrared spectroscopy. Results: The XRD analysis indicated the presence of pure Fe3O4-NPs while the TEM images indicated that the Fe3O4-NPs are spherical with a diameter range between 3.21 and 2.22 nm. The VSM study demonstrated that the magnetic properties were enhanced with the decrease in the percentage of honey. In vitro viability evaluation of Fe3O4-NPs performed by using the MTT assay on the WEHI164 cells demonstrated no significant toxicity in higher concentration up to 140.0 ppm, which allows them to be used in some biological applications such as drug delivery. Conclusion: The presented synthesis method can be used for the controlled synthesis of Fe3O4-NPs, which could be found to be important in applications in biotechnology, biosensor and biomedicine, magnetic resonance imaging and catalysis. Keywords: honey, Fe3O4 nanoparticles, green synthesis, transmission electron microscopy, magnetic properties, in vitro, viability, MTT assay, WEHI164 cell