Single-step antibiotic-mediated synthesis of kanamycin-conjugated gold nanoparticles for broad-spectrum antibacterial applications.

Widespread and irrational use of antibiotics results in the development of antibiotic-resistant bacteria. Thus, there is a need to develop novel antibacterial agents in order to replace conventional antibiotics and to increase the efficacy of already existing antibiotics by combining them with other materials. Herein, a single-step antibiotic-mediated synthesis of antibiotic-conjugated gold nanoparticles is reported. In this single-step method antibiotic Kanamycin, an aminoglycoside itself plays the role of reducing as well as capping agent by reducing gold salt into gold nanoparticles. The kanamycin-conjugated gold nanoparticles (Kan-AuNPs) were confirmed by UV-Visible spectroscopy and further physico-chemically characterized by various instrumental techniques. Synthesized Kan-AuNPs showed broad-spectrum antibacterial activity against Gram-positive Staphylococcus aureus as well as Gram-negative Escherichia coli bacterial strains. They are also found to be effective against Pseudomonas aeruginosa and pathogenic E. coli isolated from urinary tract infections (UTIs) patients, which are responsible to cause hospital-acquired infections like nosocomial, burn wound and UTIs. The minimum inhibitory concentration (MIC) of Kan-AuNPs is 50 µg ml-1 for S. aureus and E. coli, 125 µg ml-1 for P. aeruginosa and 100 µg ml-1 for E. coli isolated from UTIs patients. It is also evident that the MIC of Kan-AuNPs for antibacterial activity is lower as compared to antibiotic kanamycin alone for all bacterial strains. Hence, the one-step strategy of synthesis for Kan-AuNPs is a suitable strategy for fighting infectious bacterial strains in hospitals, healthcare and the pharmaceutical industry.

Structured superparamagnetic nanoparticles for high performance mediator of magnetic fluid hyperthermia: synthesis, colloidal stability and biocompatibility evaluation.

Core-shell structures with magnetic core and metal/polymer shell provide a new opportunity for constructing highly efficient mediator for magnetic fluid hyperthermia. Herein, a facile method is described for the synthesis of superparamagnetic LSMO@Pluronic F127 core-shell nanoparticles. Initially, the surface of the LSMO nanoparticles is functionalized with oleic acid and the polymeric shell formation is achieved through hydrophobic interactions with oleic acid. Each step is optimized to get good dispersion and less aggregation. This methodology results into core-shell formation, of average diameter less than 40 nm, which was stable under physiological conditions. After making a core-shell formulation, a significant increase of specific absorption rate (up to 300%) has been achieved with variation of the magnetization (<20%). Furthermore, this high heating capacity can be maintained in various simulated physiological conditions. The observed specific absorption rate is almost higher than Fe3O4. MTT assay is used to evaluate the toxicity of bare and core-shell MNPs. The mechanism of cell death by necrosis and apoptosis is studied with sequential staining of acridine orange and ethidium bromide using fluorescence and confocal microscopy. The present work reports a facile method for the synthesis of core-shell structure which significantly improves SAR and biocompatibility of bare LSMO MNPs, indicating potential application for hyperthermia.

Magnetic hyperthermia with magnetic nanoparticles: a status review.

Recent advances in development of potential magnetic nanoparticles for magnetic fluid hyperthermia are summarized. This review covers relation between various size dependent physical properties and their applications subject to modification in synthesis methods. Brief discussion on different heating mechanism of magnetic nanoparticles is provided. This review covers recent progress of various magnetic nanoparticles including core shell type for in vitro, in vivo and pre-clinical trials. The highlight of this review is to build up a bridge between synthesis, surface modification and in vivo- pre-clinical in magnetic fluid hyperthermia.

Enhanced colloidal stability of polymer coated La0.7Sr0.3MnO3 nanoparticles in physiological media for hyperthermia application.

Surface of La(0.7)Sr(0.3)MnO3 (LSMO) magnetic nanoparticles (MNPs) is functionalized with polymer (dextran) and their colloidal stability in various mediums is carried out. The influence of the surface functionalization of LSMO MNPs on their colloidal stability in physiological media is studied and correlated with their hyperthermia properties. Many studies have concerned the colloidal stability of MNPs coated with polymer, but their long-term stability when such complexes are exposed to physiological media is still not well understood. After zeta potential study, it is found that the dextran coating on MNPs improves the colloidal stability in water as well as in physiological media like PBS. The specific absorption rates (SAR) of these MNPs are found to be in 50-85 W/g in different concentrations of glucose and NaCl; and there values are suitable for hyperthermia treatment of cancer cells under AC magnetic field. After incorporation of MNPs up to 0.2-1mg/mL in 2 × 10(5)cells/mL (L929), the apoptosis and necrosis studies are carried out by acridine orange and ethidium bromide (AO and EB) staining and followed by visualization of microstructures under a fluorescence microscope. It is found that there are no morphological changes (i.e. no signs of cell rounding, bubble formation on the membrane and nuclear fragmentation) suggesting biocompatibility of dextran coated LSMO nanoparticles up to these concentrations.

Functionalization of La(0.7)Sr(0.3)MnO3 nanoparticles with polymer: studies on enhanced hyperthermia and biocompatibility properties for biomedical applications.

Now-a-days surface functionalized La(0.7)Sr(0.3)MnO(3) (LSMO) nanoparticles by different biocompatible polymers are attracted considerable interest in various biomedical applications in general and magnetic fluid hyperthermia treatment of cancer in particular. In this paper La(0.7)Sr(0.3)MnO(3) nanoparticles are synthesized and functionalized with polymer (dextran, with mean particle size ~25 nm). Magnetic measurements of both coated and uncoated particles reveal the superparamagnetic nature at room temperature. The resulting coated particles form a stable suspension in an aqueous environment at physiological pH and possess a narrow hydrodynamic size distribution. In vitro cytotoxicity of the MNPs has been assessed under Trypan blue dye exclusion and MTT assay on HeLa and L929 cell lines. The results demonstrate that dextran functionalized nanoparticles have no significant effect on cell viability within the tested concentrations (0.2-1 mg/mL) as compared to bare LSMO. Magnetic fluid hyperthermia studies have been done in detail; the influence of an applied alternating current (AC) magnetic field on heat generation is presented in brief. Dextran functionalized LSMO has the higher Specific absorption rate (SAR) value than the bare LSMO. After functionalization with dextran the SAR values of LSMO nanoparticles increased from 25 to 51 W/g. The study shows that the rise in temperatures by these nanoparticles could be safely controlled around Curie temperature (T(c)).

Induction heating studies of dextran coated MgFe2O4 nanoparticles for magnetic hyperthermia.

MgFe(2)O(4) nanoparticles with sizes around 20 nm have been prepared by a combustion method and functionalized with dextran for their possible applications in magnetic particle hyperthermia. The induction heating study of these nanoparticles at different magnetic field amplitudes, from 6.7 kA m(-1) to 26.7 kA m(-1), showed self-heating temperature rise up to 50.25 °C and 73.32 °C (at 5 mg mL(-1) and 10 mg mL(-1) concentrations in water respectively) which was primarily thought to be due to hysteresis losses activated by an AC magnetic field. The dextran coated nanoparticles showed a maximum specific absorption rate (SAR) of about 85.57 W g(-1) at 26.7 kA m(-1) (265 kHz). Dextran coated nanoparticles at concentrations below 1.8 mg mL(-1) exhibit good viability above 86% on mice fibroblast L929 cells. The results suggest that combustion synthesized MgFe(2)O(4) nanoparticles coated with dextran can be used as potential heating agents in magnetic particle hyperthermia. Uncoated and dextran coated samples were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric-differential thermal analysis (TG-DTA) and zeta potential-DLS studies.

The assessment and clinical implications of haloperidol acute-dose, steady-state, and withdrawal pharmacokinetics.

In order to evaluate comprehensively haloperidol pharmacokinetics under fixed-dose treatment conditions, psychiatric patients were studied after treatment with an acute dose, during maintenance therapy, and after withdrawal from haloperidol following steady-state conditions. After single doses, haloperidol appeared rapidly in serum, achieving peak concentration at a mean of 4.5 hours. The range of observed elimination half-life was broad, between 8.5 and 66.6 hours, with a mean of 19.5 hours. Under conditions of chronic dosing, serial measurements of steady-state serum concentration revealed intrapatient coefficients of variation between 2 and 72%. The mean for all patients was 26.4%. Body clearance decreased nonsignificantly, and elimination half-life increased significantly after chronic dosing compared with kinetic parameters determined after a single dose. The concentration of haloperidol in serum obtained at 8 hours after a single dose correlated most strongly (r = 0.73; p < 0.0001) with steady-state concentration resulting from chronic dosing. A value of 4 ng/ml or lower determined 8 hours after a single oral dose of 0.2 mg/kg identified patients who did not accumulate haloperidol during chronic dosing of 0.4 mg/kg per day above a presumed therapeutic range for haloperidol of 5 to 15 ng/ml. The implications of these data for the clinical use of haloperidol are discussed.

Not all that moves is tardive dyskinesia.

OBJECTIVE: Because tardive dyskinesia and spontaneous dyskinesia appear the same, it is difficult to determine whether an individual patient's abnormal movements are induced by medication or have developed spontaneously. Therefore, estimates of the prevalence of tardive dyskinesia that are based on observations not adjusted for spontaneous dyskinesia are inflated. In addition, age is thought to be an important risk factor in the development of both tardive and spontaneous dyskinesias. The authors estimate the prevalence of both disorders for specific age groups. METHOD: The authors reviewed nine reports on dyskinesia prevalence that included history of neuroleptic treatment and related prevalence to age. A rating of 2 or more on the Abnormal Involuntary Movement Scale or an equivalent score on another scale was considered an indication of dyskinesia. If the subject had taken neuroleptics for more than 3 months, the movement disorder was classified as neuroleptic-associated dyskinesia; other dyskinesias were considered spontaneous. The prevalence of tardive dyskinesia was defined as the rate of neuroleptic-associated dyskinesia minus the rate of spontaneous dyskinesia. RESULTS: The true rate of tardive dyskinesia was below 20% for all age groups except 70-79 years. The correlation between the rate of neuroleptic-associated dyskinesia and the rate of spontaneous dyskinesia was low. CONCLUSIONS: After age 40 the prevalence of spontaneous dyskinesia is sufficiently high to conclude that many patients with diagnoses of tardive dyskinesia have abnormal movements attributable to causes other than neuroleptics.