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PubMed2000

Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy.

The microscopic distribution of microspheres in human liver following hepatic infusion of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 millimetre diameter liver cancer has been investigated. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of spheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 to 1500 microm. The observed deposition patterns indicate that the vascular tumour periphery will receive much greater radiation doses from radioactive microspheres than both normal tissue and the avascular tumour centre.

Arteries↗
PubMedDate not supplied

Cochlear blood flow studied with microspheres. A comparison between two different modifications of the microsphere method.

In albino rabbits, spontaneously hypertensive rats, and guinea pigs, cochlear blood flow was measured with the microsphere method, using radioactively labelled microspheres technique and a gammaspectrometer. This 'conventional' microsphere method was compared with a new technique for measurements of cochlear blood flow: a modification of the 'radioactive' microsphere technique and the soft surface specimen technique. Values obtained for cochlear blood flow by the two different methods were similar. Consequently, the microsphere surface technique is a suitable alternative to the classical radioactive microsphere method for blood flow determinations in the cochlea.

Acid-Base Equilibrium↗
PubMedDate not supplied

Selectivity and sensitivity in the measurement of reactive oxygen species (ROS) using chemiluminescent microspheres prepared by the binding of acridinium ester or ABEI to polymer microspheres.

Two kinds of chemiluminescent microspheres were prepared as tools for measuring reactive oxygen species (ROS) released into phagosomes in phagocytizing cells, by chemically binding acridinium ester or ABEI (isoluminol derivative) to polymer microspheres, and were examined from the viewpoint of specificity and sensitivity to ROS. Acridinium ester-bound microspheres (AE-ms) were found to be a sensitive probe to superoxide anion and hydrogen peroxide under a neutral condition (pH 7.2). AE-ms emitted strong chemiluminescence (CL) by hypoxanthine (HPX)/xanthine oxidase (XOD) or hydrogen peroxide. The CL by HPX/XOD was initially inhibited by superoxide dismutase. At pH 5.6, the CL intensity from AE-ms in the presence of HPX/XOD was reduced to about one-eighth of that at pH 7.2. ABEI-bound microspheres (ABEI-ms) were found to be a selective probe for singlet oxygen although not highly sensitive. ABEI-ms emitted CL of moderate intensity with hydrogen peroxide/myeloperoxidase (MPO), but not with hydrogen peroxide alone or with hypochlorite/MPO at pH 5.6. The CL from ABEI-ms with hydrogen peroxide/MPO was completely inhibited by azide. ABEI-ms did not emit CL in the presence of HPX/XOD or by potassium superoxide at pH 5.6. The result of supplemental experiments using dissolved chemiluminescent probes and non-enzymatically generated ROS supported the above-described selectivity and sensitivity of chemiluminescent microspheres.

Acridines↗
PubMed2001

Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers.

Microspheres were prepared from poly(L-lactic acid) polymers having molecular weights between 500 and 50k g/mol. The polymers were synthesized using two initiator molecules, L-lactic acid oligomer (PLLA-LA) or stearyl alcohol (PLLA-SA). For both PLLA-LA and PLLA-SA polymers, glass (Tg) and melting (Tm) transition temperatures and enthalpy of melting all increased as the polymer molecular weight increased. PLLA-SA showed the greatest change in Tg (-13 to 54 degrees C) as molecular weight increased from 500 to 10k x g/mol, compared to 25 to 55 degrees C for PLLA-LA polymers. Changes in Tm and enthalpy of melting with increasing molecular weight were similar for both PLLA-LA and PLLA-SA. Paclitaxel release from 30% paclitaxel loaded microspheres in the size range of 50-90 microm was affected by these changes in polymer properties as molecular weight increased. As the molecular weight increased from 2k to 50k x g/mol the amount of drug released from microspheres over 14 days decreased from 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compartment model was employed. According to this model, the total amount of 'available' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and could not diffuse out at a measurable rate. Following the in vitro release study, microsphere made from 2k-10k g/mol polymers showed significant signs of disintegration whereas 50k x g/mol polymer microspheres remained intact.

Antineoplastic Agents, Phytogenic↗
PubMed1996

An alternative to radioactive microspheres for measuring regional myocardial blood flow, Part 1: Colored microspheres.

OBJECTIVE: To compare measurements of regional myocardial blood flow between color and radioactive microspheres. DESIGN: Prospective, randomized, controlled. SETTING: University research laboratory. PARTICIPANTS: Pigs. INTERVENTIONS: Pigs underwent constriction of the left anterior descending artery, either incremental and then 0 constriction with epinephrine, 0.5 to 3 mu/kg/min (n = 5; "variable") or only 0% and 100% constriction without epinephrine (n = 4, "single"). Radioactive and color microspheres were injected simultaneously. For variable constriction, 5 colors (3 x 10(6)/mL) were tested in random order and, for single, red and yellow (6 x 10(6)/2 mL). MEASUREMENTS AND MAIN RESULTS: Measurements of regional endocardial, epicardial, and transmural myocardial blood flow were compared by regression analysis (linear and nonlinear). With radioactive measurements as the point of reference, when regional flow was 50 to 150 mL/min/100 g, correlation was high (r = 0.85), although regression slope was low. With endocardial and epicardial flow between 30 and 100 mL/min/100 g, correlation was close (r = 0.84). Overall nonlinear correlation was higher with single than variable constriction (r = 0.72). When regional flow was less than 100 mL/min/100 g, linear correlation was r = 0.72. When transmural flow measured by color microspheres was less than 25 mL/min/100 g, correlation was high (r = 0.86) but, with endocardial or epicardial flow, low (r = 0.67). When transmural flow was greater than 100 mL/min/100 g, correlation was extremely low (r = 0.1; n = 26 data points). The overall correlations for regional endocardial and epicardial flows were also low, except in the ischemic zone. CONCLUSIONS: Color and radioactive measurements correlate well during moderate and ischemic regional myocardial blood flow, ischemic blood flow requiring a higher concentration of color microspheres. A major limitation of using color microspheres is imprecision when flow is greater than 150 mL/min 100 g.

Animals↗
PubMedDate not supplied

Polymers for sustained release formulations of dipyridamole-alginate microspheres and tabletted microspheres.

The preparation of dipyridamole (DIP) alginate (alg) microspheres by different methods or the incorporation of tragacanth (trgh), pectin or Eudragit L-100 55 (Eud) in alg microsphere formulations did not provide a prolonged release of DIP at pH 1.2. Tabletted microsphere formulations containing alg, trgh, pectin, sodium carboxymethyl cellulose (CMC), sodium starch glycolate (SSG), carrageenan (carrg) or Eud as diluents in different ratios, produced tablets with good physical properties which did prolong DIP release. The type, viscosity and the ratio of the diluent polymer, microsphere size and the compression pressure were found to be important factors to produce tablets with desired properties. No advantage of the tablets containing alg microspheres and granulated diluents was observed over the tablets containing powdered diluents.

Alginates↗
PubMed1994

Effects of microsphere suspension agents on systemic hemodynamics in rats. Comparison of nonradioactive colored and radioactive microspheres.

The systemic hemodynamic effects of different microsphere suspension agents were evaluated in 22 Sprague-Dawley male rats. Rats were divided into three groups, and three different solutions (distilled water; n = 7, 10% dextran; n = 8, and 70% glucose; n = 7) were injected through the left atrium respectively. 0.2 ml of each solution was injected repeatedly until significant hemodynamic changes developed. During four sequential injections, distilled water had no significant effects on cardiac output, mean arterial pressure, and heart rate. However, the 10% dextran (mol wt 70,000) solution produced significant decreases in both cardiac output and mean arterial blood pressure during and after the third injection. The 70% glucose solution also decreased, cardiac output significantly during the third injection. Although microspheres itself must cause some hemodynamic changes, our results indicated that the hemodynamic disturbances observed during a large dose injection of microspheres might have been at least in part due to the use of high-density suspending solutions. The doses of radioactive microsphere solution in many previous rat studies were usually less than 0.6 ml. However, in the case of large dose injection of microspheres, these results indicate that the suspending solutions can affect hemodynamic parameters in various ways.

Animals↗
PubMed1979

Polyglutaraldehyde: a new reagent for coupling proteins to microspheres and for labeling cell-surface receptions. II. Simplified labeling method by means of non-magnetic and magnetic polyglutaraldehyde microspheres.

Procedures were developed for the synthesis of a new immunoreagent in form of polyglutaraldehyde (PGL) microspheres in sizes ranging from about 50 nm to 1.5 micron. Addition of fluorochromes during synthesis yielded microspheres of high fluorescence intensity. By carrying out the polymerization of glutaraldehyde in presence of iron oxide, magnetic PGL microspheres were produced. Antibody conjugates obtained by interaction of PGL microspheres with immunoglobulins were used to label human red blood cells (RBC) and lymphocytes. A simple method for the separation of magnetically labeled human RBC from unlabeled cells was demonstrated.

Aldehydes↗
PubMed1994

Influence of the structure of support microspheres on leucocyte activation by RGDS-carrying microspheres.

A cell adhesive peptide, Arg-Gly-Asp-Ser (RGDS), enhances leucocyte response to stimuli when insolubilized or conjugated with proteins. In order to investigate the contribution of the microsphere structure to leucocyte response. RGDS was immobilized onto several polymeric microspheres. The respiratory burst of polymorphonuclear leucocytes (PMNs) contacting contacting microspheres was enhanced by RGDS in cases where it was immobilized on polystyrene and, more effectively, a positively charged one. This was not observed in polyacrylamide-based or negative-charged microsphere systems. These results demonstrate that the property of supports strongly affects the regulation of the PMN response via an adhesive interaction.

Amino Acid Sequence↗
PubMed2003

PLGA-PEG microspheres of teverelix: influence of polymer type on microsphere characteristics and on teverelix in vitro release.

Teverelix microspheres were produced by coacervation using a new type of poly(ester-carbonates) made of block copolymers of poly(lactic-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). Five different PLGA-PEG copolymers and one PLGA were used. The 'stability window' has been determined for all polymers. It varied depending on the molecular weight and the weight percentage of PEG. With increasing core loading (from 9.4 to 34.2%), the microparticle size increased from 10-50 to 5-1000 micrometer. The core loading did not have any influence on encapsulation yield, which remained above 80%. The influence of polymer type on microsphere characteristics was studied at two different core loadings: 9.4 and 28%. At a low core loading, the nature of the polymer had no influence on microsphere characteristics whereas at 28%, only PLGA-PEG copolymers gave acceptable microparticles in term of particle size. At 28%, the glass transition temperature (T(g)) of loaded particles was 1-8 degrees C higher than the T(g) of the corresponding polymer. Increasing the core loading increased teverelix release whereas polymer degradation was decreased. All microparticles made of PLGA-PEG copolymers showed a faster release of teverelix than PLGA-based microspheres, whatever the core loading. One PLGA-PEG was selected on the basis of in vitro release rate for further in vivo investigations.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Bioadhesive fluorescent microspheres as visible carriers for local delivery of drugs. II: Uptake of insulin-loaded PCEFB/PLGA microspheres by the gastrointestinal tract.

Uptake of novel inherently fluorescent microspheres composed of a luminescent polyanhydride, poly[p-(carboxyethylformamido)-benzoic anhydride] (PCEFB), and poly(lactide-co-glycolide) (PLGA) (2:1, weight ratio) by the gastrointestinal tract was evaluated by fluorescent microscopy. Oral efficiency of the incorporated insulin also was determined by measuring reduction of plasma glucose levels after feeding diabetic rats with a single dose of the microspheres. We found that PCEFB/PLGA microspheres could adhere to the intestinal epithelium and traverse the absorptive cells. A large number of the spheres were observed in spleen, whereas few were detected in liver within the evaluated period of time. Apparent reduction of the plasma glucose levels was observed over a span of 6 h postfeeding. The unique properties of the delivery system such as biodegradability, bioadhesivity, and inherently luminescent characteristics render it an ideal "visible" tracer for monitoring oral fate of polymeric microspheres.

Adhesives↗
PubMedDate not supplied

Embolic effects of superabsorbent polymer microspheres in rabbit renal model: comparison with tris-acryl gelatin microspheres and polyvinyl alcohol.

PURPOSE: We have developed a spherical embolic agent, superabsorbent polymer microspheres (SAP-MS). The aim of this study was to examine the embolic effects of SAP-MS in comparison with polyvinyl alcohol (PVA) particles and tris-acryl gelatin microsphere (Embosphere Microsphere; EM) in a rabbit renal model. MATERIALS AND METHODS: The right kidneys of nine rabbits were embolized with the given agents: PVA (180-300 microm) (n=3), EM (100-300 microm) (n=3), and SAP-MS (106-150 microm) (n=3). The embolized kidneys were evaluated by angiography and histology after one week. RESULTS: Renal artery occlusion and prominent coagulative necrosis were confirmed regardless of agent. PVA aggregated in the proximal vessels with tiny fragments migrating into glomeruli. Both EM and SAP-MS traveled distally up to the interlobular artery level, and a single particle achieved cross-sectional vessel occlusion. SAP-MS was markedly swollen, deformed, and conformed to the vessel lumen compared with the constantly spherical EM. Mild perivascular reaction was seen with both microspheres. CONCLUSION: SAP-MS resulted in targeted end-organ infarction in the rabbit renal model and showed different mechanical properties from other agents.

Acrylic Resins↗
PubMed1989

Applicability of an immuno-microsphere technique for a forensic identification of ABO blood types: the use of fluorescent microspheres.

In order to develop a direct micro-method for the ABO blood typing of forensic samples, an attempt has been made to utilize fluorescent immuno-microspheres. Microspheres (Covaspheres MX and CX particles, Duke Scientific) were coupled with partially purified antibodies from commercial mouse monoclonal anti-A, anti-B, and anti-H reagents, as well as with affinity purified UEA-I. The reactivity and specificity of the immuno-microspheres were checked with fresh erythrocytes of known blood groups, after which the spheres then were applied to the typing of hemolyzed and thermo-changed erythrocytes and bloodstains. The microspheres coated with the monoclonal antibodies and the UEA-I showed specific and distinct reactions with fresh, hemolyzed and thermo-changed erythrocytes, and bloodstains. Further, by combining particles labelled with different dyes, the possibility of a simultaneous double-labelling of the group antigens was indicated on the fresh cells and on the hemolyzed and thermo-changed cells and cell fragments.

ABO Blood-Group System↗
PubMed2006

Preparation of uniform silica/polypyrrole core/shell microspheres and polypyrrole hollow microspheres by the template of modified silica particles using different modified agents.

Silica/polypyrrole (PPY) core/shell microspheres and PPY hollow microspheres were prepared by the template of silica particles whose surface character was modified with different modified agents. The morphology and structure of the particles were characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Elemental analysis and X-ray photoelectron spectroscopy (XPS) were carried out to characterize the structure of PPY hollow microspheres. We investigated the effect of different modified agents on the surface character of silica particles and the effect of surface character of silica particles on the morphology of PPY hollow microspheres. The effect of reaction conditions on the size of core/shell particles and hollow particles was also studied.

Journal Article↗
PubMed1993

Microspheres for biomedical applications: preparation of reactive and labelled microspheres.

This review describes the synthesis and physico-chemical properties of reactive and labelled microspheres useful for biomedical applications. Preparation of microspheres with specific functional groups, fluorescent species, radionuclides and magnetite particles (Fe2O3) are discussed. Physico-chemical properties of microspheres, including surface charge and hydrophilicity/hydrophobicity, are also briefly covered.

Biocompatible Materials↗
PubMed1999

An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. Part 1: the influence of the dissolution medium on the drug release profile and the physical integrity of the microspheres.

The dissolution properties of stearic acid-coated cefuroxime axetil (SACA) systems have been studied with a view to investigating the effects of the dissolution medium on both the release rate and the physical integrity of the microspheres. The release from the spheres was found to be highly dependent on the media used, with systems in distilled water (pH 6.8) and pH 5.9 Sorensens modified buffer showing a relatively slow release which exhibited linearity with the square root of time, implying a diffusion process. The rate of release from systems in pH 7.0 and 8.0 buffer was considerably faster and did not follow simple diffusion kinetics. Examination of the microspheres after immersion in the various media indicated a change in the integrity of the spheres in those media which showed the most rapid release. This was particularly marked when the systems were dried in buffer, with disintegration seen in the higher pH systems. It is suggested that the release of the drug is dependent both on diffusion through the intact microspheres and changes in the physical integrity of the spheres as a result of a reaction with the surrounding medium.

Cefuroxime↗
PubMed1995

Influence of coronary venous retroinfusion and vasodilatation on regional myocardial blood flow measurement with microspheres. An analysis of 'microsphere loss' from ischaemic and reperfused porcine hearts.

The influence of coronary venous retroinfusion and a vasoselective calcium antagonist felodipine on the microsphere loss in a porcine model of myocardial ischaemia and reperfusion was studied. Sixteen open-chest pigs underwent 45 min of myocardial ischaemia induced by occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Either felodipine (felo-retro group, 7 nmol kg-1, n = 6) or the corresponding amount of vehicle (vehicle-retro group, n = 5) was infused retrogradely into the coronary veins over 30 min, starting 5 min before reperfusion. In a third group, the same amount of felodipine was administered intravenously (felo-iv group, n = 5). Myocardial regional blood flow was measured with radiolabelled microspheres (phi = 15 microns) injected before ischaemia to investigate a possible loss during ischaemia. In the felo-retro group, the apparent blood flow in the ischaemic areas, expressed as a percentage of the corresponding values in the non-ischaemic areas (%-flow), were 73 +/- 15, 73 +/- 11 and 75 +/- 19 in the subendocardial, midmyocardial and subepicardial layers, respectively. The corresponding percentage flows were 64 +/- 11, 70 +/- 11 and 62 +/- 9 in the vehicle-retro group and 75 +/- 18, 77 +/- 15 and 76 +/- 11 in the felo-iv group. The differences between the groups were not statistically significant. It is concluded that in this open-chest preparation microsphere loss observed in the ischaemic and reperfused myocardium is not increased by coronary venous retroinfusion or by a concomitantly administered vasodilative agent like felodipine.

Animals↗
PubMed1989

Preparation of zein microspheres conjugated with antitumor drugs available for selective cancer chemotherapy and development of a simple colorimetric determination of drugs in microspheres.

Zein microspheres conjugated with antitumor drugs (mitomycinc (MMC), daunomycin hydrochloride (DM), peplomycin sulfate (PEP] were prepared by using a dimethyl sulfoxide (DMSO)-H2O system. MMC with low solubility in H2O was easily entrapped by the standard procedure, whereas some modifications were required for moderately and highly soluble drugs such as DM and PEP. Colorimetric determination of the drugs in microspheres was easily achieved by use of the phenol-sulfuric acid method for drugs with sugar moieties in their molecules, such as DM and PEP, while a simple treatment of the microspheres with concentrated sulfuric acid was applied in the case of drugs having a chromophore in their molecules, such as DM and MMC.

Antineoplastic Agents↗