Showing papers in "International Journal of Nanomedicine in 2010"

Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model

Abstract: Nanomedicine concerns the use of precision-engineered nanomaterials to develop novel therapeutic and diagnostic modalities for human use. The present study demonstrates the efficacy of biologically synthesized silver nanoparticles (AgNPs) as an antitumor agent using Dalton’s lymphoma ascites (DLA) cell lines in vitro and in vivo. The AgNPs showed dose- dependent cytotoxicity against DLA cells through activation of the caspase 3 enzyme, leading to induction of apoptosis which was further confirmed through resulting nuclear fragmentation. Acute toxicity, ie, convulsions, hyperactivity and chronic toxicity such as increased body weight and abnormal hematologic parameters did not occur. AgNPs significantly increased the survival time in the tumor mouse model by about 50% in comparison with tumor controls. AgNPs also decreased the volume of ascitic fluid in tumor-bearing mice by 65%, thereby returning body weight to normal. Elevated white blood cell and platelet counts in ascitic fluid from the tumor-bearing mice were brought to near-normal range. Histopathologic analysis of ascitic fluid showed a reduction in DLA cell count in tumor-bearing mice treated with AgNPs. These findings confirm the antitumor properties of AgNPs, and suggest that they may be a cost-effective alternative in the treatment of cancer and angiogenesis-related disorders.

Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

Abstract: Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774) cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15–30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25–200 μg/mL) and up to three hours of exposure, whereas at higher concentrations (300–500 μg/mL) and prolonged (six hours) exposure viability reduced to 55%–65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H2DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS) indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury induced by nanoparticles studied using the lactate dehydrogenase assay, showed both concentration- and time-dependent damage. Thus, this study concluded that use of a low optimum concentration of superparamagnetic iron oxide nanoparticles is important for avoidance of oxidative stress-induced cell injury and death.

Toxicologic effects of gold nanoparticles in vivo by different administration routes

Abstract: Gold nanoparticles have potential applications in biomedicine, but one of the important concerns is about their safety. Most toxicology data are derived from in vitro studies and may not reflect in vivo responses. Here, an animal toxicity study of 13.5 nm gold nanoparticles in mice is presented. Animal survival, weight, hematology, morphology, and organ index are characterized at different concentrations (137.5–2200 μg/kg) over 14–28 days. The results show that low concentrations of gold nanoparticles do not cause an obvious decrease in body weight or appreciable toxicity, even after their breakdown in vivo. High concentrations of gold nanoparticles induced decreases in body weight, red blood cells, and hematocrit. It was also found that gold nanoparticles administered orally caused significant decreases in body weight, spleen index, and red blood cells. Of the three administration routes, the oral and intraperitoneal routes showed the highest toxicity, and the tail vein injection showed the lowest toxicity. Combining the results of all of these studies, we suggest that targeted gold nanopartices by tail vein injection may be suitable for enhancement of radiotherapy, photothermal therapy, and related medical diagnostic procedures.

Bactericidal effect of iron oxide nanoparticles on Staphylococcus aureus

Abstract: In order to study the effects of iron oxide (IO) nanoparticles on Staphylococcus aureus, IO nanoparticles were synthesized via a novel matrix-mediated method using polyvinyl alcohol (PVA). The IO nanoparticles were characterized by transmission electron microscopy and dynamic light scattering. Further, S. aureus were grown in the presence of three different IO nanoparticle concentrations for four, 12, and 24 hours. Live/dead assays were performed and the results provide evidence that IO/PVA nanoparticles inhibited S. aureus growth at the highest concentration (3 mg/mL) at all time points.

Recent advances in PEG–PLA block copolymer nanoparticles

Abstract: Due to their small particle size and large and modifiable surface, nanoparticles have unique advantages compared with other drug carriers. As a research focus in recent years, polyethylene glycol-polylactic acid (PEG-PLA) block copolymer and its end-group derivative nanoparticles can enhance the drug loading of hydrophobic drugs, reduce the burst effect, avoid being engulfed by phagocytes, increase the circulation time of drugs in blood, and improve bioavailability. Additionally, due to their smaller particle size and modified surface, these nanoparticles can accumulate in inflammation or target locations to enhance drug efficacy and reduce toxicity. Recent advances in PEG-PLA block copolymer nanoparticles, including the synthesis of PEG-PLA and the preparation of PEG-PLA nanoparticles, were introduced in this study, in particular the drug release and modifiable characteristics of PEG-PLA nanoparticles and their application in pharmaceutical preparations.

Visualization of interaction between inorganic nanoparticles and bacteria or fungi

Abstract: Purpose The objective of the present investigation was to evaluate the morphologic characteristics of self-assemblies of diamond (nano-D), silver (nano-Ag), gold (nano-Au), and platinum (nano-Pt) nanoparticles with Staphylococcus aureus (bacteria) and Candida albicans (fungi), to determine the possibility of constructing microorganism–nanoparticle vehicles.

Preparation, characterization, and in vitro targeted delivery of folate-decorated paclitaxel-loaded bovine serum albumin nanoparticles

Abstract: Paclitaxel (Taxol(®)) is an important anticancer drug in clinical use for treatment of a variety of cancers. Because of its low solubility, it is formulated in high concentration in Cremophor EL(®) which induces hypersensitivity reactions. In this study, targeted delivery of paclitaxel-loaded nanoparticles was prepared by a desolvation procedure, crosslinked on the wall material of bovine serum albumin, and subsequently decorated by folic acid. The characteristics of the nanoparticles, such as amount of folate conjugation, surface morphology, drug entrapment efficiency, drug loading efficiency, and release kinetics were investigated in vitro. The targeting effect was investigated in vitro by cancer cell uptake of fluorescein isothiocyanate-labeled nanoparticles. The spherical nanoparticles obtained were negatively charged with a zeta potential of about -30 mV, and characterized around 210 nm with a narrow size distribution. Drug entrapment efficiency and drug loading efficiency were approximately 95.3% and 27.2%, respectively. The amount of folate conjugation was 9.22 μg/mg of bovine serum albumin. The folate-decorated nanoparticles targeted a human prostate cancer cell line effectively.

Silver/poly (lactic acid) nanocomposites: preparation, characterization, and antibacterial activity

Abstract: In this study, antibacterial characteristic of silver/poly (lactic acid) nanocomposite (Ag/PLA-NC) films was investigated, while silver nanoparticles (Ag-NPs) were synthesized into biodegradable PLA via chemical reduction method in diphase solvent. Silver nitrate and sodium borohydride were respectively used as a silver precursor and reducing agent in the PLA, which acted as a polymeric matrix and stabilizer. Meanwhile, the properties of Ag/PLA-NCs were studied as a function of the Ag-NP weight percentages (8, 16, and 32 wt% respectively), in relation to the use of PLA. The morphology of the Ag/PLA-NC films and the distribution of the Ag-NPs were also characterized. The silver ions released from the Ag/PLA-NC films and their antibacterial activities were scrutinized. The antibacterial activi- ties of the Ag/PLA-NC films were examined against Gram-negative bacteria (Escherichia coli and Vibrio parahaemolyticus) and Gram-positive bacteria (Staphylococcus aureus) by diffusion method using Muller-Hinton agar. The results indicated that Ag/PLA-NC films possessed a strong antibacterial activity with the increase in the percentage of Ag-NPs in the PLA. Thus, Ag/PLA-NC films can be used as an antibacterial scaffold for tissue engineering and medical application.

Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

Abstract: The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined.

The application of exosomes as a nanoscale cancer vaccine

Abstract: Cancer is a leading cause of death globally, and it is predicted and projected to continue rising as life expectancy increases. Although patient survival rates for some forms of cancers are high due to clinical advances in treatment protocols, the search for effective cancer vaccines remains the ultimate Rosetta Stone in oncology. Cervarix(®), Gardasil(®), and hepatitis B vaccines are currently employed in preventing certain forms of viral cancers. However, they are, strictly speaking, not 'true' cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells. On April 2010, a new prostate cancer vaccine Provenge(®) (sipuleucel-T) was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy. Recent evidence suggests that the use of nanoscale particles like exosomes in immunotherapy could form a viable basis for the development of novel cancer vaccines, via antigen-presenting cell technology, to prime the immune system to recognize and kill cancer cells. Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development. Here, we review the current knowledge pertaining to exosome technology in immunotherapy and also seek to address the challenges and future directions associated with it, in hopes of bringing this exciting application a step closer toward an effective clinical reality.

Toxic effects of iron oxide nanoparticles on human umbilical vein endothelial cells.

Abstract: Iron oxide nanoparticles (IONPs) have been employed for hyperthermia treatments, stem cell therapies, cell labeling, and imaging modalities. The biocompatibility and cytotoxic effects of iron oxide nanoparticles when used in biomedical applications, however, are an ongoing concern. Endothelial cells have a critical role in this research dealing with tumors, cardiovascular disease and inflammation. However, there is little information dealing with the biologic effects of IONPs on the endothelial cell. This paper deals with the influence of dextran and citric acid coated IONPs on the behavior and function of human umbilical vein endothelial cells (HUVECs). After exposing endothelial cells to IONPs, dose-dependent effects on HUVECs viability, cytoskeleton and function were determined. Both citric acid and dextran coated particles appeared to be largely internalized by HUVECs through endocytosis and contribute to eventual cell death possibly by apoptosis. Cytoskeletal structures were greatly disrupted, as evidenced by diminished vinculin spots, and disorganized actin fiber and tubulin networks. The capacity of HUVECs to form a vascular network on Matrigel™ diminished after exposure to IONPs. Cell migration/invasion were inhibited significantly even at very low iron concentrations (0.1 mM). The results of this study indicate the great importance of thoroughly understanding nanoparticle-cell interactions, and the potential to exploit this understanding in tumor therapy applications involving IONPs as thermo/chemoembolization agents.

Deposition of silver nanoparticles on titanium surface for antibacterial effect

Abstract: Microbial colonization on implanted devices and biofilm formation is a recurrent complication in implant surgery and may result in loss of implants. The aim of this study was to deposit silver nanoparticles on a titanium surface to obtain antibacterial properties. In the present study, we prepared a silver nanoparticle-modified titanium (Ti-nAg) surface using silanization method. The morphology and chemical components of the Ti-nAg surface were characterized by scanning electron microscopy (SEM) equipped with energy-dispersive spectroscopy (EDS). Two species of bacteria, Staphylococcus aureus and Escherichia coli, were utilized to test the antibacterial effect of the Ti-nAg treated surface. The SEM examination revealed that a small quantity of silver nanoparticles was sparsely deposited on the titanium surface. The diameter of these nanoparticles ranged from ten to several hundred nm. EDS analyses revealed that there was 4.26% of Ag present on the surface. After a 24-hour incubation, 94% of Staphylococcus aureus and over 95% of Escherichia coli had been killed on the Ti-nAg surface, and the SEM examination of anti-adhesive efficacy test showed that there were less bacteria attached to Ti-nAg surface than to a control surface of untreated Titanium. These data suggest that silver nanoparticle-modified titanium is a promising material with an antibacterial property that may be used as an implantable biomaterial.

Green synthesis of silver/montmorillonite/chitosan bionanocomposites using the UV irradiation method and evaluation of antibacterial activity

Abstract: In this study, silver nanoparticles (Ag-NPs) were synthesized using a green physical synthetic route into the lamellar space of montmorillonite (MMT)/chitosan (Cts) utilizing the ultraviolet (UV) irradiation reduction method in the absence of any reducing agent or heat treatment. Cts, MMT, and AgNO3 were used as the natural polymeric stabilizer, solid support, and silver precursor, respectively. The properties of Ag/MMT/Cts bionanocomposites (BNCs) were studied as the function of UV irradiation times. UV irradiation disintegrated the Ag-NPs into smaller sizes until a relatively stable size and size distribution were achieved. Meanwhile, the crystalline structure and d-spacing of the MMT interlayer, average size and size distribution, surface morphology, elemental signal peaks, functional groups, and surface plasmon resonance of Ag/MMT/Cts BNCs were determined by powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, energy dispersive X-ray fluorescence, Fourier transform infrared, and UV-visible spectroscopy. The antibacterial activity of Ag-NPs in MMT/Cts was investigated against Gram-positive bacteria, ie, Staphylococcus aureus and methicillin-resistant S. aureus and Gram-negative bacteria (ie, Escherichia coli) by the disk diffusion method on Muller–Hinton Agar at different sizes of Ag-NPs. All of the synthesized Ag/MMT/Cts BNCs were found to have high antibacterial activity. These results show that Ag/MMT/Cts BNCs can be useful in different biologic research and biomedical applications, such as surgical devices and drug delivery vehicles.

Pharmacokinetic parameters and tissue distribution of magnetic Fe 3 O 4 nanoparticles in mice

Abstract: Background This study explored the pharmacokinetic parameters and tissue distribution of magnetic iron oxide nanoparticles (Fe3O4 MNPs) in imprinting control region (ICR) mice.

Atomic force microscopy probing in the measurement of cell mechanics.

Abstract: Atomic force microscope (AFM) has been used incrementally over the last decade in cell biology. Beyond its usefulness in high resolution imaging, AFM also has unique capabilities for probing the viscoelastic properties of living cells in culture and, even more, mapping the spatial distribution of cell mechanical properties, providing thus an indirect indicator of the structure and function of the underlying cytoskeleton and cell organelles. AFM measurements have boosted our understanding of cell mechanics in normal and diseased states and provide future potential in the study of disease pathophysiology and in the establishment of novel diagnostic and treatment options.

Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes.

Abstract: Single wall carbon nanotube (SWCNT) constructs were covalently appended with radiometal-ion chelates (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA] or desferrioxamine B [DFO]) and the tumor neovascular-targeting antibody E4G10. The E4G10 antibody specifically targeted the monomeric vascular endothelial-cadherin (VE-cad) epitope expressed in the tumor angiogenic vessels. The construct specific activity and blood compartment clearance kinetics were significantly improved relative to corresponding antibodyalone constructs. We performed targeted radioimmunotherapy with a SWCNT-([(225)Ac]DOTA) (E4G10) construct directed at the tumor vasculature in a murine xenograft model of human colon adenocarcinoma (LS174T). The specific construct reduced tumor volume and improved median survival relative to controls. We also performed positron emission tomographic (PET) radioimmunoimaging of the tumor vessels with a SWCNT-([(89)Zr]DFO)(E4G10) construct in the same murine LS174T xenograft model and compared the results to appropriate controls. Dynamic and longitudinal PET imaging of LS174T tumor-bearing mice demonstrated rapid blood clearance (<1 hour) and specific tumor accumulation of the specific construct. Incorporation of the SWCNT scaffold into the construct design permitted us to amplify the specific activity to improve the signal-to-noise ratio without detrimentally impacting the immunoreactivity of the targeting antibody moiety. Furthermore, we were able to exploit the SWCNT pharmacokinetic (PK) profile to favorably alter the blood clearance and provide an advantage for rapid imaging. Near-infrared three-dimensional fluorescent-mediated tomography was used to image the LS174T tumor model, collect antibody-alone PK data, and calculate the number of copies of VE-cad epitope per cell. All of these studies were performed as a single administration of construct and were found to be safe and well tolerated by the murine model. These data have implications that support further imaging and radiotherapy studies using a SWCNT-based platform and focusing on the tumor vessels as the target.

Human serum albumin nanoparticles as an efficient noscapine drug delivery system for potential use in breast cancer: preparation and in vitro analysis

Abstract: Drug delivery systems such as nanoparticles can provide enhanced efficacy for anticancer agents. Noscapine, a widely used cough suppressant for decades has recently been shown to cause significant inhibition and regression of tumor volumes without any detectable toxicity in cells or tissues. Nanoparticles made of human serum albumin (HSA) represent promising strategy for targeted drug delivery to tumor cells by enhancing the drug’s bioavailability and distribution, and reducing the body’s response towards drug resistance. In the present study, we report for the first time the incorporation and delivery of noscapine-loaded HSA nanoparticles to tumor cells. The nanoparticles were designed and optimized to achieve a particle size in the range of 150–300 nm with a drug-loading efficiency of 85%–96%. The nanoparticles were evaluated in vitro for their anticancer activity and efficacy on breast cancer cells.

Combination of calcipotriol and methotrexate in nanostructured lipid carriers for topical delivery.

Abstract: The combination of calcipotriol with methotrexate can strengthen the topical therapy for psoriasis. The aim of the present study was to evaluate the potential of nanostructured lipid carriers (NLCs) loaded with lipophilic calcipotriol and hydrophilic methotrexate as topical therapy. NLCs composed of Precirol ATO 5 with various amounts of squalene as the liquid lipid were prepared. The particle size, surface charge, molecular environment, drug permeation, and skin irritation of the carriers were assessed. Hyperproliferative skin was also used as a permeation barrier in this study. It was found that variations in the Precirol/squalene ratio had profound effects on the physicochemical characteristics of the NLCs. The range of particle size of the NLC preparations was 270 to 320 nm, with vehicles containing a higher Precirol amount exhibiting a larger diameter. NLCs with a higher Precirol/squalene ratio also showed greater polarity in their molecular environment. Calcipotriol-loaded NLC systems provided drug fluxes of 0.62 to 1.08 microg/cm(2)/h, which were slightly higher or comparable to the 30% ethanol vehicle (control, 0.72 microg/cm(2)/h). The methotrexate amount permeating the skin was 2.4 to 4.4-times greater using NLCs compared to that with the control. Dual drug-loaded NLCs exhibited reduced skin permeation of calcipotriol but not methotrexate. The in vivo topical delivery examined by confocal laser scanning microscopy (CLSM) showed a good correlation with the in vitro results. These two drugs with extremely different polarities can successfully be combined in NLCs. Results suggest that NLCs may have the potential to serve as delivery carriers for antipsoriatic drugs because of enhanced drug permeation and limited skin irritation.

Mechanical properties of dispersed ceramic nanoparticles in polymer composites for orthopedic applications.

Abstract: Ceramic/polymer composites have been considered as third-generation orthopedic biomaterials due to their ability to closely match properties (such as surface, chemistry, biological, and mechanical) of natural bone. It has already been shown that the addition of nanophase compared with conventional (or micron-scale) ceramics to polymers enhances bone cell functions. However, in order to fully take advantage of the promising nanometer size effects that nanoceramics can provide when added to polymers, it is critical to uniformly disperse them in a polymer matrix. This is critical since ceramic nanoparticles inherently have a strong tendency to form larger agglomerates in a polymer matrix which may compromise their properties. Therefore, in this study, model ceramic nanoparticles, specifically titania and hydroxyapatite (HA), were dispersed in a model polymer (PLGA, poly-lactic-co-glycolic acid) using high-power ultrasonic energy. The mechanical properties of the resulting PLGA composites with well-dispersed ceramic (either titania or HA) nanoparticles were investigated and compared with composites with agglomerated ceramic nanoparticles. Results demonstrated that well-dispersed ceramic nanoparticles (titania or HA) in PLGA improved mechanical properties compared with agglomerated ceramic nanoparticles even though the weight percentage of the ceramics was the same. Specifically, well-dispersed nanoceramics in PLGA enhanced the tensile modulus, tensile strength at yield, ultimate tensile strength, and compressive modulus compared with the more agglomerated nanoceramics in PLGA. In summary, supplemented by previous studies that demonstrated greater osteoblast (bone-forming cell) functions on well-dispersed nanophase ceramics in polymers, the present study demonstrated that the combination of PLGA with well-dispersed nanoceramics enhanced mechanical properties necessary for load-bearing orthopedic/dental applications.

Antibacterial properties of silver nanoparticles in three different sizes and their nanocomposites with a new waterborne polyurethane

Abstract: Silver nanoparticles (AgNPs) are strong bactericidal agents but they are also cytotoxic. Embedding them in a polymer matrix may reduce their cytotoxic effect. In the present study, AgNPs in three average sizes were tested for their antibacterial activities and cytotoxicity. Nanocomposites from a new waterborne polyetherurethane (PEU) ionomer and AgNPs were prepared without the use of any crosslinker. It was observed that the antibacterial activity of AgNPs against Escherichia coli started at the effective concentration of 0.1-1 ppm, while that against Staphylococcus aureus started at higher concentrations of 1-10 ppm. Cytotoxicity of AgNPs was observed at the concentration of 10 ppm. AgNPs with smaller average size showed greater antibacterial activity as well as cytotoxicity. The PEU synthesized in this study showed high tensile strength, and the addition of AgNPs at all sizes further increased its thermal stability. The delicate surface features of nanophases, however, were only observed in nanocomposites with either small-or medium-sized AgNPs. PEU-Ag nanocomposites had a strong bacteriostatic effect on the growth of E. coli and S. aureus. The proliferation of endothelial cells on PEU-Ag nanocomposites was enhanced, whereas the platelet adhesion was reduced. The expression of endothelial nitric oxide synthase gene was upregulated on PEU-Ag containing small-sized AgNPs (30 ppm) or medium-sized AgNPs (60 ppm). This effect was not as remarkable in nanocomposites from large-sized AgNPs. Overall, nanocomposites from the PEU and 60 ppm of the medium-sized (5 nm) AgNPs showed the best biocompatibility and antibacterial activity. Addition of smaller or larger AgNPs did not produce as substantial an effect in PEU, especially for the larger AgNPs.

Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer.

Abstract: The goal of this study was to develop near-infrared (NIR) resonant gold-gold sulfide nanoparticles (GGS-NPs) as dual contrast and therapeutic agents for cancer management via multiphoton microscopy followed by higher intensity photoablation. We demonstrate that GGS-NPs exposed to a pulsed, NIR laser exhibit two-photon induced photoluminescence that can be utilized to visualize cancerous cells in vitro. When conjugated with anti-HER2 antibodies, these nanoparticles specifically bind SK-BR-3 breast carcinoma cells that over-express the HER2 receptor, enabling the cells to be imaged via multiphoton microscopy with an incident laser power of 1 mW. Higher excitation power (50 mW) could be employed to induce thermal damage to the cancerous cells, producing extensive membrane blebbing within seconds leading to cell death. GGS-NPs are ideal multifunctional agents for cancer management because they offer the ability to pinpoint precise treatment sites and perform subsequent thermal ablation in a single setting.

Magnetic nanoformulation of azidothymidine 5'-triphosphate for targeted delivery across the blood-brain barrier.

Abstract: Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.

Progress in antiretroviral drug delivery using nanotechnology.

Abstract: There are currently a number of antiretroviral drugs that have been approved by the Food and Drug Administration for use in the treatment of human immunodeficiency virus (HIV). More recently, antiretrovirals are being evaluated in the clinic for prevention of HIV infection. Due to the challenging nature of treatment and prevention of this disease, the use of nanocarriers to achieve more efficient delivery of antiretroviral drugs has been studied. Various forms of nanocarriers, such as nanoparticles (polymeric, inorganic, and solid lipid), liposomes, polymeric micelles, dendrimers, cyclodextrins, and cell-based nanoformulations have been studied for delivery of drugs intended for HIV prevention or therapy. The aim of this review is to provide a summary of the application of nanocarrier systems to the delivery of anti-HIV drugs, specifically antiretrovirals. For anti-HIV drugs to be effective, adequate distribution to specific sites in the body must be achieved, and effective drug concentrations must be maintained at those sites for the required period of time. Nanocarriers provide a means to overcome cellular and anatomical barriers to drug delivery. Their application in the area of HIV prevention and therapy may lead to the development of more effective drug products for combating this pandemic disease.

Iodine-125 radiolabeling of silver nanoparticles for in vivo SPECT imaging

Abstract: Silver nanoparticles are increasingly finding applications in medicine; however, little is known about their in vivo tissue distribution. Here, we have developed a rapid method for radiolabeling of silver nanoparticles with iodine-125 in order to track in vivo tissue uptake of silver nanoparticles after systemic administration by biodistribution analysis and single-photon emission computerized tomography (SPECT) imaging. Poly(N-vinyl-2 -pyrrolidone)-capped silver nanoparticles with an average size of 12 nm were labeled by chemisorption of iodine-125 with a > 80% yield of radiolabeling efficiency. Radiolabeled silver nanoparticles were intravenously injected in Balb/c mice, and the in vivo distribution pattern of these nanoparticles was evaluated by noninvasive whole-body SPECT imaging, which revealed uptake of the nanoparticles in the liver and spleen. Biodistribution analysis confirmed predominant accumulation of the silver nanoparticles in the spleen (41.5%ID/g) and liver (24.5%ID/g) at 24 h. Extensive uptake in the tissues of the reticuloendothelial system suggests that further investigation of silver nanoparticle interaction with hepatic and splenic tissues at the cellular level is critical for evaluation of the in vivo effects and potential toxicity of silver nanoparticles. This method enables rapid iodine-125 radiolabeling of silver nanoparticles with a specific activity sufficient for in vivo imaging and biodistribution analysis.

Synthesis of silver/montmorillonite nanocomposites using γ-irradiation

Abstract: Silver nanoparticles (Ag-NPs) were synthesized into the interlamellar space of montmorillonite (MMT) by using the γ-irradiation technique in the absence of any reducing agent or heat treatment. Silver nitrate and γ-irradiation were used as the silver precursor and physical reducing agent in MMT as a solid support. The MMT was suspended in the aqueous AgNO3 solution, and after the absorption of silver ions, Ag+ was reduced using the γ-irradiation technique. The properties of Ag/MMT nanocomposites and the diameters of Ag-NPs were studied as a function of γ-irradiation doses. The interlamellar space limited particle growth (d-spacing [ds] = 1.24–1.42 nm); powder X-ray diffraction and transmission electron microscopy (TEM) measurements showed the production of face-centered cubic Ag-NPs with a mean diameter of about 21.57–30.63 nm. Scanning electron microscopy images indicated that there were structure changes between the initial MMT and Ag/MMT nanocomposites under the increased doses of γ-irradiation. Furthermore, energy dispersive X-ray fluorescence spectra for the MMT and Ag/ MMT nanocomposites confirmed the presence of elemental compounds in MMT and Ag-NPs. The results from ultraviolet-visible spectroscopy and TEM demonstrated that increasing the γ-irradiation dose enhanced the concentration of Ag-NPs. In addition, the particle size of the Ag-NPs gradually increased from 1 to 20 kGy. When the γ-irradiation dose increased from 20 to 40 kGy, the particle diameters decreased suddenly as a result of the induced fragmentation of Ag-NPs. Thus, Fourier transform infrared spectroscopy suggested that the interactions between Ag-NPs with the surface of MMT were weak due to the presence of van der Waals interactions. The synthesized Ag/MMT suspension was found to be stable over a long period of time (ie, more than 3 months) without any sign of precipitation.

Types of neural guides and using nanotechnology for peripheral nerve reconstruction

Abstract: Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed.

Synthesis and characterization of silver/talc nanocomposites using the wet chemical reduction method

Abstract: In this study, silver nanoparticles (Ag-NPs) were synthesized using the wet chemical reduction method on the external surface layer of talc mineral as a solid support. Silver nitrate and sodium borohydride were used as the silver precursor and reducing agent in talc. The talc was suspended in aqueous AgNO(3) solution. After the absorption of Ag(+) on the surface, the ions were reduced with NaBH(4). The interlamellar space limits were without many changes (d(s) = 9.34-9.19 A(o)); therefore, Ag-NPs formed on the exterior surface of talc, with d(ave) = 7.60-13.11 nm in diameter. The properties of Ag/talc nanocomposites (Ag/talc-NCs) and the diameters of the Ag-NPs prepared in this way depended on the primary AgNO(3) concentration. The prepared Ag-NPs were characterized by ultraviolet-visible spectroscopy, powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and Fourier transform infrared. These Ag/talc-NCs may have potential applications in the chemical and biological industries.

Nanomedicine: promises and challenges for the future of public health.

Abstract: As the scope of nanotechnology applications in medicine evolves, it is important to simultaneously recognize and advance contributions germane to public health. A wide range of innovations in nanomedicine stand to impact nearly every medical specialty and unveil novel ways to improve the quality and extend the duration of life – these gains can be measured at both individual and population levels. For example, heart disease and cancer combined make up approximately half of all deaths in the United States per year, and already, advances in nanomedicine demonstrate great potential to reduce rates of morbidity and mortality due to these diseases. Meanwhile, public health applications of nanomedicine such as rapid and portable diagnostics and more effective vaccinations have the potential to revolutionize global health. Research driven by innovators across disciplines such as engineering, biology, medicine, and public health should collaborate in order to achieve maximal potential impact in health for individuals and populations. In turn, knowledge gaps regarding the potential health and safety implications of exposure to engineered nanomaterials must be continuously addressed and actively researched. Dynamic, proactive, and socially responsible research will drive nanomedicine as it plays an increasingly integral and transformative role in medicine and public health in the 21st century.

Investigation of interactions between poly-l-lysine-coated boron nitride nanotubes and C2C12 cells: up-take, cytocompatibility, and differentiation

Abstract: Boron nitride nanotubes (BNNTs) have generated considerable interest within the scientific community by virtue of their unique physical properties, which can be exploited in the biomedical field. In the present in vitro study, we investigated the interactions of poly-l-lysine-coated BNNTs with C2C12 cells, as a model of muscle cells, in terms of cytocompatibility and BNNT internalization. The latter was performed using both confocal and transmission electron microscopy. Finally, we investigated myoblast differentiation in the presence of BNNTs, evaluating the protein synthesis of differentiating cells, myotube formation, and expression of some constitutive myoblastic markers, such as MyoD and Cx43, by reverse transcription – polymerase chain reaction and Western blot analysis. We demonstrated that BNNTs are highly internalized by C2C12 cells, with neither adversely affecting C2C12 myoblast viability nor significantly interfering with myotube formation.

Stability and antimicrobial effect of amikacin-loaded solid lipid nanoparticles

Abstract: Solid lipid nanoparticles (SLNs) of amikacin were designed in this study for pulmonary delivery to reduce the dose or its administration intervals leading to reduction of its toxicities especially in long term treatment. Nanoparticles of amikacin were prepared from cholesterol by solvent diffusion technique and homogenization. The size, zeta potential, loading efficiency, and release profile of the nanoparticles were studied. The conventional broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) and minimum bacteriostatic concentration (MBC) of amikacin SLNs with respect to Pseudomonas aeruginosa in vitro. To guarantee the stability of desired SLNs, they were lyophilized using cryoprotectants. Results showed that considering the release profile of amikacin from the studied nanocarrier, MIC and MBC of amikacin could be about two times less in SLNs of amikacin compared to the free drug. Therefore, fewer doses of amikacin in SLNs can clear the infection with less adverse effects and more safety. Particle size enlargement after lyophilization of desired SLNs after two months storage was limited in comparison with non-lyophilized particles, 996 and 194 nm, respectively. Zeta potential of lyophilized particles was increased to +17 mV from +4 mV before lyophilization. Storage of particles in higher temperature caused accelerated drug release.