Mohammad Imani

Graphene: Promises, Facts, Opportunities, and Challenges in Nanomedicine

Nanomedicine Hong Ying Mao,† Sophie Laurent,‡ Wei Chen,*,†,§ Omid Akhavan, Mohammad Imani, Ali Akbar Ashkarran, and Morteza Mahmoudi* †Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore ‡Department of General, Organic, and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, Avenue Maistriau, 19, B-7000 Mons, Belgium Department of Physics, National University of Singapore, 2 Science Drive 3, Singapore 117542, Singapore Department of Physics, Sharif University of Technology, P.O. Box 11155-9161, Tehran, Iran Institute for Nanoscience and Nanotechnology, Sharif University of Technology, P.O. Box 14588-89694, Tehran, Iran Novel Drug Delivery Systems Department, Iran Polymer and Petrochemical Institute, Tehran, Iran Department of Physics, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Department of Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell medium components. For this purpose, uncoated and polyvinyl alcohol (PVA) coated SPIONs with narrow size distribution were synthesized via a well-known coprecipitation method. The mouse fibroblast cell line L929 was exposed to SPIONs to probe the toxicity of magnetic nanoparticles during the bio application. Changes to the cell medium caused by SPIONs were analyzed with zeta potential measurements, ultraviolet visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that gas vesicles are formed in SPION-treated cells. Toxicity is conventionally explained by changes in the DMEMs pH and composition due to the tendency of SPIONs to interact with biomolecules. A new procedure is proposed to examine the in vitro toxicity of nanoparticles in a more rigorous manner, which gives an improvement in the relationship between in vivo and in vitro toxicity studies.

Optimal design and characterization of superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol for targeted delivery and imaging.

Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were prepared by a coprecipitation technique using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the effect of different synthesis parameters (stirring rate and base molarity) on the structure, morphology, saturation magnetization, purity, size, and size distribution of the synthesized magnetite nanoparticles was studied by various analysis techniques including X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) with differential scanning calorimetry (DSC) measurements, vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), UV-visible, and Fourier transform infrared (FT-IR) spectrometer. PVA not only stabilized the colloid but also played a role in preventing further growth of SPION followed by the formation of large agglomerates by chemisorption on the surface of particles. A rich behavior in particle size, particle formation, and super paramagnetic properties is observed as a function of molarity and stirring conditions. The particle size and the magnetic properties as well as particle shape and aggregation (individual nanoparticles, magnetic beads, and magnetite colloidal nanocrystal clusters (CNCs) are found to be influenced by changes in the stirring rate and the base molarity. The formation of magnetic beads results in a decrease in the saturation magnetization, while CNCs lead to an increase in saturation magnetization. On the basis of the DOE methodology and the resulting 3-D response surfaces for particle size and magnetic properties, it is shown that optimum regions for stirring rate and molarity can be obtained to achieve coated SPION with desirable size, purity, magnetization, and shape.

An in vitro study of bare and poly(ethylene glycol)-co-fumarate-coated superparamagnetic iron oxide nanoparticles: a new toxicity identification procedure

As the use of superparamagnetic iron oxide nanoparticles (SPION) in biomedical applications increases (e.g. for targeting drug delivery and imaging), patients are likely to be exposed to products containing SPION. Despite their high biomedical importance, toxicity data for SPION are limited to date. The aim of this study is to investigate the cytotoxicity of SPION and its ability to change cell medium components. Bare and poly(ethylene glycol)-co-fumarate (PEGF)-coated SPION with narrow size distributions were synthesized. The particles were prepared by co-precipitation using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Dulbeccos modified Eagles medium (DMEM) and primary mouse fibroblast (L929) cell lines were exposed to the SPION. Variation of cell medium components and cytotoxicity due to the interactions with nanoparticles were analyzed using ultraviolet and visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay methods, respectively. The toxicity amount has been traditionally identified by changes in pH and composition in cells and DMEM due to the tendency of SPION to adsorb proteins, vitamins, amino acids and ions. For in vitro toxicity assessments, a new surface passivation procedure is proposed which can yield more reliable quantitative results. It is shown that a more reliable way of identifying cytotoxicity for in vitro assessments is to use particles with saturated surfaces via interactions with DMEM before usage.

RECENT ADVANCES IN SURFACE ENGINEERING OF SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES FOR BIOMEDICAL APPLICATIONS

Superparamagnetic iron oxide nanoparticles (SPIONs) are promising materials for various biomedical applications including targeted drug delivery and imaging, hyperthermia, magneto-transfections, gene therapy, stem cell tracking, molecular/cellular tracking, magnetic separation technologies (e.g. rapid DNA sequencing), and detection of liver and lymph node metastases. The most recent applications for SPIONs for early detection of inflammatory, cancer, diabetes and atherosclerosis have also increased their popularity in academia. In order to increase the efficacy of SPIONs in the desired applications, especial surface coating/characteristics are required. The aim of this article is to review the surface properties of magnetic nanoparticles upon synthesis and the surface engineering by different coatings. The biological aspects, cytotoxicity, and health risks are addressed. Special emphasis is given to organic and inorganic-based coatings due to their determinant role in biocompatibility or toxicity of the final particles.

Chitosan/polyethylene glycol fumarate blend film: physical and antibacterial properties.

The objective of this work was to prepare chitosan/polyethylene glycol fumarate (chitosan/PEGF) blend films as wound dressings and to evaluate the influence of composition ratio on the blending properties of the films. Blending chitosan with PEGF obviated the brittleness of neat chitosan film. Film topography performed by atomic force microscopy illustrated that blending could increase and control the surface roughness of the neat film. Their water vapor transmission rates were close to the range of 904-1447 g(-2)day(-1) found to be proper candidates for dressing the wounds with moderate exudates. Controlled water solubility, swelling, wettability and surface tension of the blend films were also evaluated. The blend films showed a powerful antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus (Kill%>99.76 ± 0.16%). Physical properties as well as antibacterial activity assessments showed that among different compositions, the film comprising 80 wt% chitosan and 20 wt% PEGF is a suitable candidate for biomedical applications as a wound dressing material.

Fabrication and characterization of poly(D,L-lactide-co-glycolide)/hydroxyapatite nanocomposite scaffolds for bone tissue regeneration.

Conventional methods in fabrication of scaffolds based on polymer/bioceramic composites frequently make use of solution casting then particle leaching. The residues of common organic solvents can get trapped in this technique hence provide safety concerns on final scaffold. In this study, N-methyl pyrrolidone was used as an approved solvent for parenteral pharmaceutical products especially implants with acceptable toxicological profile. A combined freeze drying and solvent casting methods were adopted for complete removal of the solvent from final scaffold structure. Biodegradable scaffolds based on poly (D,L-lactide-co-glycolide) and different percentages of nanohydroxyapatite (25, 35, and, 45% w/w) were characterized thoroughly regarding porosity, pore distribution as well as their bioactivity and biocompatibility. The results showed 70-80% porosity with a size distribution in the range of 50-200 mum for different conditions. Bioactivity of the scaffolds was directly dependent on the bioceramic content in the samples according to the results. Composites and neat samples showed the same cytocompatibility profile. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Injectable in situ forming drug delivery system based on poly(ε-caprolactone fumarate) for tamoxifen citrate delivery: Gelation characteristics, in vitro drug release and anti-cancer evaluation

The present study deals with the preparation and characterization of an injectable and in situ forming drug delivery system based on photocrosslinked poly(epsilon-caprolactone fumarate) (PCLF) networks loaded with tamoxifen citrate (TC). Networks were made of PCLF macromers, a photoinitiation system (comprising initiator and accelerator) and the active ingredient N-vinyl-2-pyrrolidone (NVP) as a crosslinker and reactive diluent. Shrinkage behavior, equilibrium swelling and sol fraction ratios of photocrosslinked PCLF gels were determined as functions of NVP content. It was shown that the crosslinking is facilitated up to a certain concentration of NVP and most of NVP remained unreacted above this value. In vitro drug release, biocompatibility evaluation and activity against MCF-7 breast cancer cell line were also investigated. Accurate but simple bipartite expressions were also derived that enable rapid determination of effective diffusion coefficients of TC in photocrosslinked PCLF/NVP disks. Cytotoxicity assay showed that while the photocrosslinked PCLF network with optimum NVP content exhibits no significant cytotoxicity against MCF-7 and L929 cell lines, 40-60% of the MCF-7 cells were killed after incubation with TC-loaded devices.

Poly(acrylic acid) grafted montmorillonite as novel fillers for dental adhesives: Synthesis, characterization and properties of the adhesive

OBJECTIVE This work investigates the graft polymerization of acrylic acid onto nanoclay platelets to be utilized as reinforcing fillers in an experimental dental adhesive. Physical and mechanical properties of the adhesive and its shear bond strength to dentin are studied. The effect of the modification on the stability of the nanoparticle dispersion in the dilute adhesive is also investigated. MATERIALS AND METHODS Poly(acrylic acid) (PAA) was grafted onto the pristine Na-MMT nanoclay (Cloisite(®) Na(+)) through the free radical polymerization of acylic acid in an aqueous media. The resulting PAA-g-nanoclay was characterized using FTIR, TGA and X-ray diffraction (XRD). The modified nanoclays were added to an experimental dental adhesive in different concentrations and the morphology of the nanoclay layers in the photocured adhesive matrix was studied using TEM and XRD. Shear bond strength of the adhesives containing different filler contents was tested on the human premolar teeth. The stability of nanoclay dispersion in the dilute adhesive was also studied using a separation analyzer. The results were then statistically analyzed and compared. RESULTS The results confirmed the grafting reaction and revealed a partially exfoliated structure for the PAA-g-nanoclay. Incorporation of 0.2 wt.% of the modified nanoclay into the experimental adhesive provided higher shear bond strength. The dispersion stability of the modified nanoparticles in the dilute adhesive was also enhanced more than 25 times. SIGNIFICANCE Incorporation of the modified particles as reinforcing fillers into the adhesive resulted in higher mechanical properties. The nanofiller containing bonding agent also showed higher shear bond strength due to the probable interaction of the carboxylic acid functional groups on the surface of the modified particles with hydroxyapatite of dentin.

Corticosteroid‐releasing cochlear implant: A novel hybrid of biomaterial and drug delivery system

In this study, drug-eluting cochlear implant (CI) electrodes were prepared, and the amount of drug released was determined. Dexamethasone (DEX) (0.25-2% w/w, the weight percent of the final cured polymer) was used as a bioactive agent to suppress postsurgical inflammations upon mixing with a two-part nonrestricted pourable medical-grade silicone elastomer. Batch reproducibility analysis was performed on three consecutive batches. Drug release experiments were accomplished in normal saline medium, where DEX was analyzed via a validated HPLC method. The drug loading percentage and the device surface area were the most dominant parameters explored to monitor the drug release behavior from CI coatings. Total cumulative amount of DEX released from various loaded samples was in the order of 2 > 1 > 0.5 > 0.35 > 0.25% w/w, but the cumulative percentage of drug released showed a reverse order. The DEX dosages between 0.1 and 1 microg were released from samples of smallest to highest loadings during the initial 24 h, and dosages <1-5 microg were released from similar samples of various loadings at the first patency 2 weeks. The extent of crosslinking was only effective on release profile at lower drug loadings of 0.25% w/w relative to 0.5%. It was also found that release profile was not affected by postcuring. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.