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PubMed2004

Preparation of naltrexone hydrochloride loaded poly (DL-lactide-co-glycolide) microspheres and the effect of polyvinyl alcohol (PVA) as surfactant on the characteristics of the microspheres.

The aim of this study was to investigate the effect of the surfactant properties of polyvinyl alcohol (PVA) in enhancing the yield of small size microspheres. Naltrexone microspheres were prepared by solvent-solvent extraction evaporation process. PVA of various concentrations were added into the aqueous phase prior to the mixing process. The addition of PVA was expected to influence the shape, size distribution, drug loading and drug release profile. The results indicated that it is desirable to increase the weight fraction of the microspheres with size range below 106 mm for the highest possible yield.

Delayed-Action Preparations↗
PubMed2006

Multilayered polymer microspheres by thermal imprinting during microsphere growth.

Modulation of the polymerization temperature in precipitation polymerizations was used to form onion-type polymer microspheres consisting of multiple nested layers. Specifically, the copolymerization of chloromethylstyrene and divinylbenzene-55 in acetonitrile, at temperatures ramping between 65 and 75 degrees C, led to monodisperse, cross-linked microspheres of about 10 mum diameter that have radial density profiles closely reflecting the thermal profiles used. This thermal imprinting is attributed to the copolymer formed being close to its theta point during the polymerization. As the microspheres grow by continuously capturing oligomers from solution, the resulting transient surface gel layer expands and contracts with temperature, and thus records the reaction temperature profile in the form of a corresponding density profile, even as it cross-links.

Journal Article↗
PubMed1999

Differing susceptibility of echocardiographic contrast agents to adverse effects of biologic factors: multicenter, videodensitometric comparison of octafluoropropane-filled microspheres with air-filled microspheres for left ventricular opacification.

BACKGROUND: Echocardiographic contrast enhancement of the left ventricle has diagnostic value in the assessment of regional and global left ventricular (LV) function. The efficacy of both octafluoropropane-filled human albumin microbubbles (OCTA) and of air-filled human albumin microbubbles (AIR) for LV endocardial delineation and qualitative LV opacification has previously been reported. However, pulmonary disease, obesity, impaired LV function, and decreased echogenicity may diminish the efficacy of contrast agents for LV opacification. The purpose of this study was to compare the susceptibility of 2 contrast agents currently approved by the Food and Drug Administration to these biologic factors. METHODS: To compare quantitative LV opacification with OCTA (0.2, 0. 5, 3.0, 5.0 mL) versus AIR (0.08 mL/kg, 0.22 mL/kg), we performed videodensitometry in 199 patients (average age 59.2 +/- 13.3 years, 79% men) studied in 2 identical, prospective, multicenter, blinded trials, of whom 74 had impaired LV function, pulmonary disease, or both, 70 were obese (body mass index >30 kg/m(2)), and 45 were nonechogenic (>/=4 of 6 endocardial segments were not seen in the apical 4-chamber view). Changes in videodensity from noncontrast to contrast agent with the same gain settings were determined at end diastole and end systole (gray scale 0 to 255 U) for 2 regions of interest: left ventricle apex-to-mid-cavity and mid-cavity-to-base. The relative influence of clinically evident pulmonary disease, impaired LV function on echocardiography, and echogenicity on LV opacification produced by both contrast agents was determined by multivariate analysis. RESULTS: Significant videodensity increases ranging from 67% to 143% were observed with both agents. At the recommended initial doses (0.5 mL for OCTA, 0.22 mL/kg for AIR), OCTA produced greater opacification than AIR in both regions of interest and at both phases of the cardiac cycle. Poor LV function was associated with decreased LV opacification for AIR but not for OCTA. Diminished echogenicity was more strongly associated with impaired opacification for AIR than for OCTA. Obesity and clinically evident pulmonary disease were associated with diminished chamber opacification with both OCTA and AIR. CONCLUSIONS: In addition to the superiority of octafluoropropane-filled microspheres to air-filled microspheres for LV opacification, the efficacy of OCTA is relatively unaffected by impaired LV function and is less susceptible to the effects of poor echogenicity than AIR.

Albumins↗
PubMed1984

Specific removal of digoxin by hemoperfusion through agarose polyacrolein microsphere polyacrolein microsphere beads-antidigoxin antibodies (APAMB-AD).

The efficacy of a new, biocompatible, specific immunosorbent for hemoperfusive removal of digoxin is described. The sorbent contains antidigoxin antibodies covalently bound to polyacrolein microspheres, 0.2 mu diam. Thousands of microspheres are matrix-encapsulated in crosslinked agarose to form beads of 500 to 800 mu diam. Digoxin intoxicated dogs showed heart block, ventricular and atrial tachycardia and extended runs of PVCs. During hemoperfusion the abnormal ECG abated; at 2 h of hemoperfusion the ECG tracings returned to normal. Up to 25% of the total digoxin burden was removed. The numbers of the blood cells and the content of a battery of relevant soluble components of the blood remained constant. Dogs were alive and well after the hemoperfusion. Non hemoperfused dogs, which received antiarrythmic agents, did not survive the intoxication. This is the first report of a practical hemoperfusive system for the specific removal of digoxin from whole blood.

Acrolein↗
PubMed1999

Mechanisms of hepatic disposition of polystyrene microspheres in rats: effects of serum depend on the sizes of microspheres.

To study the mechanisms of the hepatic disposition of polystyrene microspheres (MS), effects of serum on their hepatic disposition characteristics were investigated for MSs with particle sizes of 50 nm (MS-50) and 500 nm (MS-500) by isolated liver perfusion experiments. It was revealed that serum in the perfusate inhibited and promoted the hepatic disposition of MS-50 and MS-500 at 37 degrees C, respectively. However, pre-heating at 56 degrees C or pre-treatment with anti-C3 antibody of serum reduced the promotive effect of serum on the hepatic uptake of MS-500, suggesting that the complement system should be involved as opsonins for the hepatic uptake of MS-500. Hepatic disposition of both MSs at 4 degrees C was reduced by the addition of serum into the perfusate, which could be ascribed to the reduction of the surface hydrophobicity of MSs due to the adsorption of serum proteins onto the surface of MSs and to resultant decrease in non-specific disposition to the liver. From these results, serum was found to function both as the opsonin to enhance the hepatic uptake of MSs and as the inhibitor by reducing non-specific interaction between MSs and the plasma membrane. Whether serum promotes or inhibits the hepatic disposition of MSs would be dependent on the particle sizes of MSs.

Animals↗
PubMed2000

An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. III. The use of DSC and HSDSC as means of characterising the interaction of the microspheres with buffered media.

Stearic acid coated cefuroxime axetil (SACA) microspheres have been studied using differential scanning calorimetry (DSC) and high sensitivity DSC (HSDSC) in order to examine the interaction between the spheres and a range of buffer systems, with a view to further enhance the understanding of the mechanism of drug release developed in earlier studies [Robson et al., 1999, 2000]. DSC studies indicated that after immersion in Sorensens modified phosphate buffer (SMPB) pH 5.9 followed by washing and drying, no change in the thermal properties of the spheres was detected up to 60 min of immersion, with a single endotherm noted at circa 56 degrees C, that corresponded to the melting of the stearic acid used in this study; similar results were obtained for systems immersed in distilled water. After immersion in SMPB pH 7.0 and 8.0, however, a second peak was noted at approximately 67 degrees C that increased in magnitude relative to the lower temperature endotherm with increasing exposure time to the medium. Spheres that had not been previously washed prior to drying showed complete conversion to the higher temperature endotherm for these two buffers. Systems which had been exposed to a range of pH 7.0 buffers (citrate-phosphate buffer (CPB), phosphate buffer mixed (PBM), boric acid buffer (BAB)) were then examined. Only the CPB systems showed evidence for conversion to the higher melting form. PBM systems to which further sodium had been added were then examined. A maximum conversion was found at 0.05 M sodium, which was in agreement with the maximum in release rate found in a previous study [Robson et al., 2000]. HSDSC was then used to examine systems that were immersed in the buffer. For SMPB, pH 5.9 and distilled water, only the endotherm corresponding to the stearic acid melting was seen. However, for SMPB pH 7.0 and 8.0, three peaks were seen, two corresponding to those seen for the DSC studies and a further lower temperature peak at circa 44 degrees C. Studies on PBM systems to which additional sodium had been added showed small levels of conversion to the higher temperature form at higher sodium contents. The data was discussed in terms of the correlation with earlier dissolution studies on the same systems [Robson et al., 1999; 2000].

Buffers↗
PubMed1992

Poly(L-lactic acid) microspheres containing neutron-activatable holmium-165: a study of the physical characteristics of microspheres before and after irradiation in a nuclear reactor.

The solvent evaporation technique was employed to prepare poly(L-lactic acid) (PLA) microspheres with 165Ho acetylacetonate (Ho-AcAc). Particle size, percentage Ho-165, percent residual solvent, and retentive ability of the spheres were found to be strongly affected by preparatory conditions. Differential scanning calorimetry (DSC) thermograms suggested that the Ho-AcAc existed in the PLA matrix as a molecular dispersion. High neutron flux irradiations of the PLA spheres in a nuclear reactor produced Ho-166, a therapeutic radionuclide that emits high-energy negatrons (Emax = 1.84 MeV; half-life = 26.9 hr). The gamma radiation dose (53-75 Mrad) from the core of the reactor provided an overkill of all bioburdens in the PLA spheres. Gel permeation chromatography (GPC) analysis showed that these irradiations caused a reduction in PLA molecular weight. Infrared spectra, 13C NMR spectra, 1H NMR spectra, and DSC thermograms further confirmed the presence of lower molecular weight PLA but proved the overall maintenance of PLA structure.

Bacillus↗
PubMed2005

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres.

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 microm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 microm, with the mean diameter of 5 microm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.

Anti-Inflammatory Agents↗
PubMed1998

Fluorescent microspheres are superior to radioactive microspheres in chronic blood flow measurements.

The accuracy of the fluorescent (FM) and radioactive microsphere (RM) techniques is similar in acute experiments but has not been established in chronic experiments. In the present study various combinations (at least pairs) of FM and/or RM labels were injected simultaneously between 2 mo and 5 min before each animal was killed. Blood flow was determined in many organs. Intramethod mean difference and variation did not change over time for FM but increased significantly for RM (from 1.8 +/- 1.4 to 25.6 +/- 21.8% and from 4.4 +/- 3.2 to 32.4 +/- 23.0% at 5 min and 2 mo, respectively). Also the FM-RM intermethod mean difference and variation increased (from -0.5 +/- 8.5 to 40.8 +/- 23.8% and from 23. 6 +/- 4.6 to 71.8 +/- 34.3%, respectively). After 2 mo, blood flow estimations were 20-50% lower with the various RM, whereas brain and liver blood flow values varied even more between isotopes. Underestimation started within 1 day for 51Cr and within 2 wk for 141Ce, 95Nb, and 85Sr. We conclude that FM are superior to RM for blood flow determination in experiments lasting longer than 1 day, presumably because of leaching of isotopes from RM.

Animals↗
PubMed1997

[Study of magnetic microspheres for purging cancer cells from bone marrow. II. Preparation of polystyrene magnetic microspheres. ].

Magnetic microspheres (MS) used to purge tumor cells from human bone marrow were prepared with a two step method. Main factors that can influence the magnetization result were discussed. The MS were coated with polyacrolein which has active aldehyde group. The magnetic material content and the magnetic response of MS were determined and showed that the magnetic material y-Fe(2)O(3) by X-ray diffraction.

Acrolein↗
PubMed1994

The Microspheres based Detoxification System (MDS). A new extracorporeal blood purification technology based on recirculated microspherical adsorbent particles.

Plasma sorption processes have so far been performed with filters and appropriate adsorption columns. In this paper, we introduce a newly developed plasma sorption system, which is based on the high adsorption capacity of microspheres in a recirculation system. The technology has been applied successfully in vitro to eliminate endotoxins, low density lipoproteins (LDL) and barbiturates from human plasma.

Animals↗