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Novel high relaxivity colloidal particles based on the specific phase organisation of amphiphilic gadolinium chelates with cholesterol.

To obtain high T(1)-relaxivity colloidal particles with a simultaneously high loading of amphiphilic Gd-chelates, a novel drug dosage form based on the phase organisation of amphiphilic gadolinium chelates with cholesterol was developed. In order to find a formulation, which exhibit both high T(1)-relaxivity and gives small particles a D-optimal mixture design (experimental design) was applied. Gadolinium 1,4,7-tris(carboxymethyl)-10-(2-hydroxyhexadecyl)-1,4,7,10-tetraazacyclododecane (Gd-HHD-DO3A) and cholesterol at approximately equimolar ratio proved to form thermodynamic stable disc-like colloidal particles as seen by cryo-electron micrographs. T(1)-relaxivity of these particles was typically around 20mM(-1)s(-1) and the size below 100 nm (photon correlation spectroscopy (PCS)). The particles do most probably not interact with blood components as no change in T(1)-relaxivity was observed when the particles were mixed with whole blood. The particles were stable at room temperature for at least 6 months.

Cholesterol↗

Electrochemical detection of DNA immobilized on gold colloid particles modified self-assembled monolayer electrode with silver nanoparticle label.

The target DNA was immobilized successfully on gold colloid particles associated with a cysteamine monolayer on gold electrode surface. Self-assembly of colloidal Au onto a cysteamine modified gold electrode can enlarge the electrode surface area and enhance greatly the amount of immobilized single stranded DNA (ssDNA). The electron-transfer processes of [Fe(CN)6](4-)/[Fe(CN)6](3-) on the gold surface were blocked due to the procedures of the target DNA immobilization, which was investigated by impedance spectroscopy. Then single stranded target DNA immobilized on the gold electrode hybridized with the silver nanoparticle-oligonucleotide DNA probe, followed by the release of the silver metal atoms anchored on the hybrids by oxidative metal dissolution, and the indirect determination of the released solubilized Ag(I) ions by anodic stripping voltammetry (ASV) at a carbon fiber microelectrode. The results show that this method has good correlation for DNA detection in the range of 10-800 pmol/l and allows the detection level as low as 5 pmol/l of the target oligonucleotides.

Cross-Linking Reagents↗

Saccharated colloidal iron enhances lipopolysaccharide-induced nitric oxide production in vivo.

We investigated the effects of iron on the production of nitric oxide (NO), inducible NO synthase (iNOS), and plasma cytokines induced by lipopolysaccharide (LPS) in vivo. Male Wistar rats were preloaded with a single intravenous injection of saccharated colloidal iron (Fesin, 70 mg iron/kg body weight) or normal saline as a control, and then given an intraperitoneal injection of LPS (5.0 mg/kg body weight). Rats, preloaded with iron, had evidence of both iron deposition and strong iNOS induction in liver Kupffer cells upon injection of LPS; phagocytic cells in the spleen and lung had similar findings. LPS-induced NO production in iron-preloaded rats was significantly higher than control rats as accessed by NO-hemoglobin levels measured by ESR (electron spin resonance) and NOx (nitrate plus nitrite) levels. Western blot analysis showed that iron preloading significantly enhanced LPS-induced iNOS induction in the liver, but not in the spleen or lung. LPS-induced plasma levels of IL-6, IL-1beta, and TNF-alpha were also significantly higher in iron-preloaded rats as shown by ELISA, but IFN-gamma levels were unchanged. We conclude that colloidal-iron phagocytosed by liver Kupffer cells enhanced LPS-induced NO production in vivo, iNOS induction in the liver, and release of IL-6, IL-1beta, and TNF-alpha.

Animals↗

Effect of colloidal carriers on ascorbyl palmitate stability.

Active compounds can be protected against degradation by incorporation into colloidal carrier systems. The stabilizing effect of carrier systems for ascorbyl palmitate (AP) was investigated using microemulsions (ME), liposomes and solid lipid nanoparticles (SLN). Analysis of chemical stability by HPLC showed that AP is most resistant against oxidation in non-hydrogenated soybean lecithin liposomes, followed by SLN, w/o and o/w ME, and hydrogenated soybean lecithin liposomes. The molecular environment of the AP-like nitroxide probe (C(16)-Tempo) in colloidal carriers was characterized using electron paramagnetic resonance (EPR) spectroscopy. We have found that the nitroxide groups are located in environments with different polarity and mobility. The hydrophilic part of AP is the reactive moiety, and high stability is obtained in systems in which this part is exposed to a less polar environment. Additionally, the determined accessibility of nitroxide groups to reduction correlated well with the chemical stability of AP. It is more deeply immersed in the interface when entrapped in a liquid-state carrier than when applied in gel-state particles. Encapsulation of AP in SLN core leads to greater stability. We conclude that the location of the sensitive group of the drug-molecule in a carrier system is crucial for its stability.

Ascorbic Acid↗

The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa.

The influence of the surface characteristics of colloidal drug carriers in their interaction with different biological surfaces is becoming increasingly evident. In order to investigate the importance of these characteristics in their interaction with the ocular mucosa, we developed three types of nanocapsules that differ in their surface properties: poly- epsilon -caprolactone (PECL) nanocapsules, chitosan (CS)-coated PECL nanocapsules and poly(ethylene glycol) (PEG)-coated PECL nanocapsules. Two different approaches were used to form these polymer coated nanocapsules: (i) the electrostatic anchorage of the coating onto the PECL nanocapsules-in the case of CS-and (ii) the use of the previously synthesized copolymer PECL-PEG for the formation of the nanocapsules. In both cases, the systems, prepared by the interfacial deposition technique, were loaded with a fluorescent dye (rhodamine) in order to quantify and visualize their interaction with the ocular surface ex vivo and in vivo. An important conclusion from the ex vivo studies is that the developed systems, and specially the CS-coated ones, enhanced the penetration of the encapsulated dye through the cornea. This effect was not simple due to the physical presence of the nanocapsules but to their ability to carry the encapsulated compound. The second conclusion from the confocal laser scanning microscopy (CLSM) studies is that the systems were able to enter the corneal epithelium by a transcellular pathway and that the penetration rate was dependent on the coating composition. The images suggest that the PEG coating accelerates the transport of the nanocapsules across the whole epithelium, whereas the CS coating favours the retention of the nanocapsules in the superficial layers of the epithelium. The specific behaviour of CS-coated systems was also corroborated in vivo. These results indicate that the surface composition of colloidal drug carriers affects their biodistribution in the eye. Therefore, this surface modification approach can be used as a targeting strategy in ocular drug delivery.

Animals↗

Ozone disinfection dynamics of enteric viruses provide evidence that infectious titer reduction is triggered by alterations to viral colloidal properties.

The inactivation dynamics of three enteric virus species (polio-, rota- and parvovirus) were analysed in different aqueous suspensions by using O3 under continuous flow conditions. A mathematical model for the reaction rate of infectious titer reduction was proposed, based on the thermodynamic principles of phase behaviour of colloids suspended in aqueous environments. Up to a certain threshold dosage of residual ozone (RO), and depending on the type of test virus and the ionic or organic load in the stock suspension, the logarithm of the reaction rate constant of viral inactivation rate was observed to vary in a rather sigmoidal manner with log RO concentration. Data from photon correlation spectroscopy, electron microscopy and tensiometric analysis suggested that below the threshold RO, the pattern of virus inactivation dynamics reflects the varying potential of different-sized viral particles (VPs) to adsorb to the cellular monolayer. There is strong evidence that oxidant-induced surface activity of organic matter causes redistribution of VP infectivity. This hypothesis was statistically corroborated inasmuch as experimental inactivation data proved to be satisfactorily fitted by a logistic equation. It was concluded that viral infection, and thus viral inactivation, is a complex process which is governed largely by the classical laws of colloidal behaviour. The latter is suggested to appreciably determine the capability of inoculated VPs to infect host cultures. This notion may especially be cause for concern when regulatory requirements for virus disinfection are being based on titration results from in vitro testing procedures.

Animals↗

Reagentless glucose biosensor based on direct electron transfer of glucose oxidase immobilized on colloidal gold modified carbon paste electrode.

The direct electrochemistry of glucose oxidase (GOD) adsorbed on a colloidal gold modified carbon paste electrode was investigated. The adsorbed GOD displayed a pair of redox peaks with a formal potential of -(449+/-1) mV in 0.1 M pH 5.0 phosphate buffer solution. The response showed a surface-controlled electrode process with an electron transfer rate constant of (38.9+/-5.3)/s determined in the scan rate range from 10 to 100 mV/s. GOD adsorbed on gold colloid nanoparticles maintained its bioactivity and stability. The immobilized GOD could electrocatalyze the reduction of dissolved oxygen and resulted in a great increase of the reduction peak current. Upon the addition of glucose, the reduction peak current decreased, which could be used for glucose detection with a high sensitivity (8.4 microA/mM), a linear range from 0.04 to 0.28 mM and a detection limit of 0.01 mM at a signal-to-noise ratio of 3sigma. The sensor could exclude the interference of commonly coexisted uric and ascorbic acid.

Biosensing Techniques↗

Application of impedance spectroscopy for monitoring colloid Au-enhanced antibody immobilization and antibody-antigen reactions.

We used colloidal Au to enhance the amount of antibody immobilized on a gold electrode and ultimately monitored the interaction of antigen-antibody by impedance measurement. Self-assembly of 6 nm (diameter) colloidal Au onto the self-assembled monolayers (SAMs) of 4-aminothiophenol modified gold electrode resulted in an easier attachment of antibody. The redox reactions of [Fe(CN)6](4-)/[Fe(CN)6](3-) on the gold surface were blocked due to the procedures of self-assembly of 4-aminothiophenol and antibody immobilization, which were investigated by cyclic voltammetry and impedance spectroscopy. The interaction of antigen with grafted antibody recognition layers was carried out by soaking the modified electrode into a phosphate buffer at pH 7.4 with various concentrations of antigen at 37 degrees C for 30 min. The antibody recognition layers and their interactions with various concentrations of antigen could be detected by measurements of the impedance change. The results show that this method has good correlation for detection of Hepatitis B virus surface antigen in the range of 0.5-200 microg/l and a detection limit of about 50 ng/l.

Adsorption↗

Colloids versus crystalloids for emergency patients.

Emergency as well as critical care nurses are often responsible for the administration and regulation of fluid resuscitation for their patients. A serious and potentially fatal decline in vital organ performance can often occur as a result of inappropriate volume management. However, emergency and/or critically ill patients who require fluid resuscitation often receive concurrent therapy and monitoring that may have equal or greater impact on the survival and therapeutic end points than does the type of fluid received. These variables have made historical comparisons of crystalloid versus colloid resuscitation difficult. The purpose of this article is to critique three articles that examine crystalloid and colloid resuscitation for patients with various disease processes.

Colloids↗

Concordance and validation study of sentinel lymph node biopsy for breast cancer using subareolar injection of blue dye and technetium 99m sulfur colloid.

BACKGROUND: We have previously demonstrated the utility, accuracy, and advantages of a subareolar (SA) site of injection for blue dye compared with an intraparenchymal site. In later studies we advocated the additional use of preoperative SA-injected technetium 99m-labeled sulfur colloid as a directional aid in finding blue-stained sentinel lymph nodes (SLNs). Paramount to the usefulness of this dual-tracer, same-site technique is the degree to which SA-injected blue dye and SA-injected radiocolloid migrate concordantly and are deposited within the same sentinel nodes. The purpose of this study was to document the correlation and accuracy of SLN biopsy using blue dye and radiocolloid when both nodal markers are injected by the same SA route. STUDY DESIGN: Between September 1999 and February 2002 (29 months), 185 consecutive patients with 187 operable breast cancers underwent 187 attempted SLN biopsies by a dual-tracer, same-site injection technique using the SA approach for both agents. Unfiltered technetium 99m-labeled sulfur colloid (1 mCi [37 MBq]) was SA-injected 30 to 45 minutes preoperatively; and just after anesthetic induction, 3 mL of 1% isosulfan blue dye was injected by the same SA route. SLN biopsies or complete axillary dissections were carried out, and SLNs identified during these procedures were classified as containing both blue dye and radioactivity ("blue-hot" nodes), radioactivity alone ("hot-only" nodes), or blue dye alone ("blue-only" nodes). Cases were categorized and tabulated based on the presence or absence of these three types of SLNs. RESULTS: Of the 187 procedures, a SLN was identified successfully in 184 cases, indicating an SLN identification rate of 98.4% (95% confidence interval, 96.6% to 100.2%). In these 184 cases, a blue-hot node was present in 94.5% (n = 174 of 184). An SLN was positive in 50 cases, or 27.2% of the total group (n = 50 of 184). A blue-hot node was the only positive SLN in 43 of these 50 cases, or 86% of the node-positive cases. There were no false negatives in 20 confirmatory axillary node dissections carried out to document the findings of a negative SLN. A correlation analysis revealed that in 98.9% of cases (174 of 176), blue nodes were also radioactive ("blue-hot" case concordance = 98.9%). In 95.1% of cases (174 of 183), hot nodes had also taken up blue dye ("hot-blue" case concordance = 95.1%). CONCLUSIONS: Using SA injections of both blue dye and radiocolloid, we achieved an SLN identification rate of 98.4% (184 of 187 cases), a false-negative rate of 0% (0 of 20 cases), and an accuracy in predicting the malignant status of the axilla of 100% (70 of 70 cases). The case concordance rate ranged between 98.9% ("blue-hot concordance") and 95.1% ("hot-blue concordance"). The present study is the first to evaluate dual-tracer, same-site SA injections of blue dye and radiocolloid. By demonstrating a high case concordance rate, a high SLN identification rate, and a 0% false-negative rate, this study adds further support to the validity and accuracy of same-site SA injections of both blue dye and radiocolloid during SLN biopsy in breast cancer.

Adult↗

Sentinel lymphadenectomy for breast cancer: experience with 180 consecutive patients: efficacy of filtered technetium 99m sulphur colloid with overnight migration time.

BACKGROUND: Axillary node status remains the most important prognostic indicator of survival in breast cancer patients. Only 25% to 35% of patients having standard level I/II axillary dissection have involved nodes, yet all accept the potential for morbidity after the operation. This study was conducted to assess whether status of the sentinel node(s) was an accurate predictor of the presence of metastatic disease in axillary or internal mammary nodes. STUDY DESIGN: In 180 patients, technetium 99m sulphur colloid was injected in a 4-quadrant peritumoral distribution. During the first phase of the study, 72 patients had sentinel node excision followed by a level I/II axillary dissection. During the second phase of the study, 108 patients had sentinel node excision and only those with positive nodes had completion axillary dissection. Nodes were examined after formalin fixation by taking 10 sections at 20-microm intervals and staining with hematoxylin-eosin. RESULTS: Sentinel nodes were found in 162 (90%) of 180 patients. The mean number of sentinel nodes examined was 3.1. Of the 162 patients with successful lymphatic mapping, positive sentinel nodes were found in 44 (27%). In 23 (66%) of 35 patients with positive sentinel nodes who had a completion level I/II axillary dissection, the sentinel nodes were the only positive nodes. The concurrent negative predictive value was 4% in the first 72 patients who had completion axillary dissection after sentinel node excision, and 2% for the entire series. With evolution of technique, identification of sentinel nodes with radiolabeled colloid was successful in 97% of the last 100 patients. CONCLUSIONS: Because the concurrent negative predictive value was low, sentinel node excision appeared to accurately identify node status, potentially avoiding the need for standard level I/II axillary dissection in sentinel node-negative patients.

Axilla↗

Semi-quantitative analysis of indigo carmine, using silver colloids, by surface enhanced resonance Raman spectroscopy (SERRS).

The application of surface enhanced resonance Raman spectroscopy (SERRS) to the semi-quantitative analysis of the dye, indigo carmine, has been examined using citrate-reduced silver colloids. Good linear correlations are observed for the dye band at 1580 cm(-1) in the concentration range 10(-7)-10(-5) and 10(-9)-10(-5) mol dm(-3), using laser exciting wavelengths of 514.5 [(R=0.9983)] and 632.8 nm [(R=0.9978)], respectively. At concentrations of dye above 10(-6) M the concentration dependence of the SERRS signals is non-linear due to the coverage of the surface of the colloidal particles by the dye being in excess of a full monolayer. At concentrations above 10(-6) M resonance Raman spectroscopy (RRS) can be employed for the quantitative analysis of the dye. An internal standard was used and a good linear correlation (R=0.997) was observed for the dependence of dye signal intensities at 1580 cm(-1) in the concentration range 10(-5)-10(-4) M using a laser exciting wavelength of 514.5 nm. The limits of detection of indigo carmine by SERRS (514.5 nm), SERRS (632.8 nm) and solution RRS (514.5 nm) are found to be 0.9, 1 and 38 ppm, respectively.

Colloids↗

Semi-quantitative analysis of indigo by surface enhanced resonance Raman spectroscopy (SERRS) using silver colloids.

In this paper we report for the first time semi-quantitative analysis of indigo using surface enhanced Raman spectroscopy (SERS) and surface enhance resonance Raman spectroscopy (SERRS). Indigo, a dye widely used today in the textile industry, has been used, historically, both as a dye and as a pigment; the latter in both paintings and in printed material. The molecule is uncharged and largely insoluble in most solvents. The application of SERS/SERRS to the semi-quantitative analysis of indigo has been examined using aggregated citrate-reduced silver colloids with appropriate modifications to experimental protocols to both obtain and maximise SERRS signal intensities. Good linear correlations are observed for the dependence of the intensities of the SERRS band at 1151 cm(-1) using laser exciting wavelengths of 514.5 nm (R=0.9985) and 632.8 nm (R=0.9963) on the indigo concentration over the range 10(-7)-10(-5) and 10(-8)-10(-5) mol dm(-3), respectively. Band intensities were normalised against an internal standard (silver sol band at 243 cm(-1)). Resonance Raman spectra (RRS) of aqueous solutions of indigo could not be collected because of its low solubility and the presence of strong fluorescence. It was, however, possible to obtain RS and RRS spectra of the solid at each laser excitation wavelength. The limits of detection (L.O.D.) of indigo by SERS and SERRS using 514.5 and 632.8 nm were 9 ppm at both exciting wavelengths. Signal enhancement by SERS and SERRS was highly pH dependent due to the formation of singly protonated and possibly doubly protonated forms of the molecule at acidic pH. The SERS and SERRS data provide evidence to suggest that an excess of monolayer coverage of the dye at the surface of silver colloids is observed at concentrations greater than 7.85x10(-6) mol dm(-3) for each exciting wavelength. The data reported herein also strongly suggest the presence of multiple species of the indigo molecule.

Colloids↗

Intra- and extravascular volume status in patients undergoing mitral valve replacement: crystalloid vs. colloid priming of cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Cardiopulmonary bypass is associated with changes of intra- and extravascular volume status often resulting in cardiopulmonary dysfunction. The purpose of this prospective double-blind study was to evaluate the influence of different priming solutions of the extracorporeal circuit on intra- and extravascular volume status and haemodynamics in patients undergoing elective mitral valve replacement. METHODS: Twenty-two patients with mitral valve insufficiency were randomly allocated into two equal groups. In Group 1 cardiopulmonary bypass was primed with a nearly isooncotic solution consisting of 4% albumin. The second group received a pure crystalloid priming solution. The thermo-dye indicator dilution technique was used for the assessment of cardiac output, central and pulmonary blood volume, right ventricular end-diastolic volume and total blood volume. RESULTS: Patients in the crystalloid group showed increased intraoperative fluid requirements. Significantly more fluid was accumulated in the extravascular space whereas total blood volume was decreased after surgery. Stroke volume index (SVI) was significantly decreased in the immediate postoperative period when compared to baseline. As indicated by the increase in extravascular fluid content after surgery, both colloid and crystalloid priming volumes were transferred to the extravascular space. CONCLUSION: The use of colloid priming solutions in patients with mitral valve insufficiency leads to less fluid requirements and significantly reduced fluid shift in the interstitium. However, these changes are not associated with changes in haemodynamic parameters or short term outcome.

Adrenergic beta-Agonists↗

Surface-enhanced Raman analysis of sulfa drugs on colloidal silver dispersion.

Surface-enhanced Raman spectrometry (SERS) of three sulfa drugs (sulfadiazine, sulfamerazine, and sulfamethazine) is reported. Silver colloidal dispersions prepared by simple borohydride reduction of silver nitrate are used as substrates. The capability of SERS for spectral fingerprinting of analytes with close structural properties using easily prepared substrates and relatively simple instrumentation is illustrated. By careful attention to the timing in the measurement, quantitative information can be obtained from silver colloids. Linearity was achieved up to 100 ng mL-1. Limits of detection range in the low nanograms per milliliter level.

Colloids↗

A colloidal graphite-coated emitter for sheathless capillary electrophoresis/nanoelectrospray ionization mass spectrometry.

A colloidal graphite-coated emitter is introduced for sheathless capillary electrophoresis/nanoelectrospray ionization time-of-flight mass spectrometry (CE/ESI-TOFMS). The conductive coating can be produced by brushing the capillary tip to construct a fine layer of 2-propanol-based colloidal graphite. The fabrication involves a single step and requires less than 2 min. Full cure properties develop in approximately 2 h at room temperature and then the tip is ready for use. The coated capillary tip is applied as a sheathless electrospray emitter. The emitter has proven to bear stable electrospray and excellent performance for 50 microm i.d. x 360 microm o.d. and 20 microm i.d. x 360 microm o.d. capillaries within the flow rate of 80-500 nL/min; continuous electrospray can last for over 200 h in positive mode. Baseline separation and structure elucidation of two clinically interesting basic drugs, risperidone and 9-hydroxyrisperidone, are achieved by coupling pressure-assisted CE to ESI-TOFMS using the described sheathless electrospray emitter with a bare fused-silica capillary at pH 6.7. It is found that the signal intensity of m/z in sheathless CE/ESI-TOFMS at pH 6.7 is approximately 50 times higher than that at pH 9.0 for the two analytes, although the electroosmotic flow (EOF) at pH 9.0 provides sufficient flow rate (approximately 150 nL/min) to maintain electrospray.

Colloids↗

Electromigration of single molecules of DNA in a crystalline array of 300-nm silica colloids.

The velocities and conformations of single DNA chains were probed as they electromigrated at varying electric field strength through a crystalline array of silica colloids. An optically transparent film consisting of 300-nm silica colloids was formed on glass as a transparent crystalline layer of 7 mum thickness with an effective pore size of 45 nm. The behaviors of individual lambda-DNA molecules (48,502 base pairs) electromigrating through this material were observed to be analogous to the behaviors of long DNA chains in electrophoresis gels, including chain extension, hooking of chains around the matrix, and hernia formation. The electrophoretic mobility of lambda-DNA in this dense, narrow-pore material is surprisingly high: 1.8 cm2/Vs at 10 V/cm, which is at least as high as for much wider-pore gels. Imaging of the single molecules revealed that higher field strength caused increased chain extension and increased mobility, which reached an apparent plateau just above 2.0 cm2/Vs at 200 V/cm. Pulsed, crossed electric fields of 200 V/cm at 120 degrees to one another were applied to the material. The DNA chains were observed by imaging to electromigrate in an orderly fashion, and the migration rate was found to be length-dependent. The results indicate that these thin, robust, self-assembling inorganic materials are interesting as possible alternatives to polymeric gels for higher speed electrophoresis.

Bacteriophage lambda↗