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At least 865 records · Page 48Linked to original sources
PubMed2004

Microsphere-induced embolic stroke: an MRI study.

Despite the many studies of the middle cerebral artery occlusion (MCAO) model, efficient therapy for stroke is still lacking, emphasizing the need for further development and characterization of experimental stroke models. In the present study, the rather unexplored multifocal microsphere-induced stroke model in rats was characterized by multiparametric MRI. We induced microembolic infarction in a group of Sprague-Dawley rats by injecting a dose of about 1000 50-microm polyethylene microspheres intracranially from the external carotid artery. Diffusion-, perfusion-, and T(2)-weighted MRI were used to evaluate the infarct development during and following the first 3 hr after microsphere injection (N = 20). The animals were also imaged at 12-hr (N = 8), 24-hr (N = 17), and 48-hr (N = 5) time points. After the final imaging time point, the brains were removed and sectioned into 2-mm-thick slices, and infarct volumes were measured by 2,3,4-triphenyltetrazolium chloride (TTC) staining. From calculated apparent diffusion coefficient (ADC) maps, a volume of reduced ADC appeared 0.5-1.0 hr postinjection, and by the 3-hr time point the volume of ADC reduction had increased to a size of 5% +/- 1% (mean +/- SEM) of the brain hemisphere. The lesion volume increased significantly (P < 0.01) to 16% +/- 2% of the hemisphere volume at the 12-hr time point, while at 24 hr the lesion (15% +/- 2% of the hemisphere) was also significantly larger (P < 0.001) than at 3 hr. The perfusion deficit resulting from the microsphere injection was immediate, going from a cerebral blood flow index (CBF(i)) of 74% +/- 3% at the time of microsphere injection to 68% +/- 2% of the contralateral mean at 3 hr (P < 0.05), to 55% +/- 4% of the contralateral values at 12 hr (P < 0.05), and to 57% +/- 2% of the contralateral mean at 24 hr (P < 0.001). The lesion development in the microsphere-induced stroke model was found to be slower than in the MCAO model, and continued up to the 24-48-hr time point.

Animals↗
PubMed2001

Ethyl cellulose polymer microspheres for controlled release of norfluazon.

The pesticide norfluazon has been microencapsulated using ethyl cellulose to develop controlled-release formulations that decrease its mobility through the soil and protect it from photodegradation. Ethyl cellulose microspheres loaded with norfluazon were prepared by the solvent-evaporation method. To obtain the microspheres, certain conditions (pesticide/polymer ratio, percentage of emulsifying agent and solvent) were varied. The shape and size of the microspheres obtained were studied by scanning electron microscopy. Other parameters, such as solids recovery, encapsulation efficiency and pesticide loading, were also studied. The release rate of norfluazon from the different microspheres was slower than that of pure norfluazon. In particular, microspheres obtained with o-xylene, which provided the largest diameter, retarded the initial release of the pesticide relative to microspheres obtained with chloroform, or to pure norfluazon. Moreover, the studies showed that the pesticide/polymer ratio controlled the release of norfluazon, which was slower when this ratio was low. Release rates conformed to a generalised kinetic equation for a diffusion-controlled release mechanism, and the time taken for 50% of the active ingredient to be released into water, t50, was calculated.

Acrylic Resins↗
PubMed1996

Estimation of antigenic tetanus toxoid extracted from biodegradable microspheres.

Microspheres made from poly (lactic/glycolic acid) polymers have been considered as a new delivery system for single-dose tetanus toxoid (TT) vaccines. One of the most critical properties of the proposed vaccines is the loading and distribution of TT as this will have a profound effect on immunogenicity. As the concentration of TT in microspheres is very low sensitive assay methods are required. An assay incorporating monoclonal antibody (MAb) recognizing a neutralizing epitope and cross-reacting with TT was developed (MAp capture ELISA) which provided a sensitivity of 0.001 Lf/ml. An extraction procedure was devised which did not destroy the antigenicity and gave a recovery of 90.6 +/- 3.39% when applied to different preparations. The extracted TT was then quantified by MAb capture ELISA which was estimated to be 250-fold more sensitive than single-site ELISA for toxoid. The loading of 20 microspheres preparations (12 filled and 8 placebo) was determined by both protein micro-BCA assay and the developed assay for TT. The TT content obtained for the 12 filled microspheres preparations from different sources varied up to 400-fold (range 0.01-4.0 Lf/mg microspheres). The utility of the MAb capture ELISA for detection of total antigenic content in microspheres was confirmed by the observation that the determine TT loading correlated with the theoretical loading predicted from the protein content for the best preparations. Preparations with high loading gave the greatest peak response. There was no relationship between dose and the in vivo immunogenic response, suggesting that encapsulated vaccines with differential loading, release properties and presence of excipients will have different response curves in vivo. Hence, the present assay, when combined with information on toxoid release rate and presence and effect of excipients may be of value in predicting in vivo response.

Animals↗
PubMed2000

Macrophage activation for the production of immunostimulatory cytokines by delivering interleukin 1 via biodegradable microspheres.

Interleukin 1alpha (IL-1alpha), a pleiotropic cytokine with multiple anti-tumour activities, has been investigated in our laboratory for its potential to serve as an immunotherapeutic agent. In the present study, an attempt was made to direct IL-1alpha to macrophages, in order to induce their immunoregulatory activities. For that purpose, IL-1alpha was encapsulated within biodegradable poly(lactic/glycolic acid) microspheres, 1-5 microm diameter in size. The microspheres were efficiently taken-up by macrophages in culture and after intraperitoneal injection into mice. In culture, phagocytosis of the microspheres reached saturation within 3 h and there was no apparent effect of polymer type on the extent of uptake. In vivo uptake of human IL-1alpha-microspheres by the macrophages lead to cell activation, as evidenced by the enhanced production of murine IL-1alpha, IL-6 and IL-12. Control microspheres, containing bovine serum albumin, induced only background to low levels of cytokine production. These cytokines, when expressed by or secreted from macrophages, may stimulate in situ diverse immune and inflammatory responses, including T cell-mediated immune responses, such as the development of Th(1)cells and cytotoxic lymphocytes. Thus, directing IL-1alpha into macrophages, via the appropriate microspheres, may serve as a unique mean to activate these cells to participate in anti-tumour immune responses in situ.

Animals↗
PubMed1999

Use of cefazolin microspheres to treat localized methicillin-resistant Staphylococcus aureus infections in rats.

BACKGROUND: In a previous study, the topical administration of biodegradable, controlled-release poly-(dl-lactide-co-glycolide) cefazolin microspheres could effectively prevent surgical wound infections with a sensitive strain of Staphylococcus aureus in an experimental animal model. The objective of the current study was to evaluate and compare the efficacy of topical antibiotic therapy with cefazolin microspheres to systemic cefazolin therapy for the treatment of experimental rat surgical wounds contaminated with a methicillin-resistant strain of S. aureus (MRSA). METHODS: A local infection model in rats was used. MRSA was used to infect pockets surgically produced in the paraspinous muscles. Groups of rats received either topical cefazolin microspheres, topical cefazolin powder, parenteral cefazolin, or no treatment. Feces were cultured to evaluate the effect of antibiotic therapy on gut flora. RESULTS: The rate of clinical wound infection following topical application of cefazolin microspheres (13%) was significantly lower than the 53% infection rate observed in rats who had received a 2-week course of systemic cefazolin therapy (P = 0.046). Moreover, single-dose topical antibiotic therapy with cefazolin microspheres completely eradicated MRSA from the wounds of 7 of 15 (47%) animals. There was no statistically significant difference, however, in the rate of clinical wound infection between rats whose wounds were treated topically with free cefazolin powder and those treated with systemic cefazolin (P = 0.12). Importantly, selection of antibiotic-resistant bacteria was associated with systemic but not local cefazolin therapy. CONCLUSION: The results of this study suggest that topical antibiotic therapy with controlled-release cefazolin microspheres may be effective for the prevention of wound infection with both methicillin-sensitive and methicillin-resistant strains of S. aureus in selected surgical procedures that are at high risk of developing postoperative wound infection.

Administration, Topical↗
PubMed2000

A probabilistic model for ligand-cytoskeleton transmembrane adhesion: predicting the behavior of microspheres on the surface of migrating cells.

A theoretical model describing the attachment and cytoskeletal coupling of microspheres to the dorsal surface of motile cells was developed. Integral membrane receptors beneath a ligand-coated microsphere are allowed to be either free, attached to the microsphere, bound to the rearward moving actin network, or linked to both the bead and the cytoskeleton, and to switch between these four states. The binding transitions being modeled as chemical reactions governed by rate constants taken from literature, the chance for a receptor to be in each binding state over time is obtained by solving mass-balance equations for the probability functions. The population of n such receptors beneath the microsphere is accounted for by a binomial distribution for each state. Adhesion and transmembrane coupling (resulting in microsphere transport) being defined by a minimal number of ligand-receptor and receptor-cytoskeleton bonds, respectively, the probabilities of attachment and transport of the microsphere over time are expressed in terms of state probability distributions. It is found that increasing the ligand density raises the attachment and transport probabilities, in good quantitative agreement with recent experiments using optical tweezers and accurate position tracking. Increasing the bead size does not affect attachment, but raises the transport probability with a marked transition for bead diameter around 100 nm, as for experimental data. Increasing the restraining force decreases the transport probability, probably by inducing a rupture of receptor-cytoskeleton bonds. This study thus provides a framework that helps understand the process of cortical flow associated with cell locomotion.

Animals↗
PubMed1975

The radioactive microsphere method for the assessment of regional myocardial blood flow after coronary artery occlusion. Inaccuracies due to variations in the diameter distribution of the spheres.

In this study, we have tried to determine the magnitude of the inaccuracy of the radioactive microsphere method - due to variations in the diameter distribution of the spheres - for measuring regional myocardial blood flow after coronary artery occlusion. In 5 mongrel dogs, three types of 15 mum microspheres, labelled with 125I, 141Ce or 85Sr, were injected simultaneously after the descending branch of the left coronary artery had been ligated. Myocardial samples wert taken from the left ventricle and divided into four groups according to the number of spheres per sample. The radioactivity of the various isotopes per gram tissue was expressed as percentage of their activity per milliliter of the reference sample. The diameter distribution of microspheres, labelled with each of the isotopes, was determined light-microscopically in suspensions belonging to three different batches. The relative error, as determined from the difference in relative radioactivity of the various types of microspheres in the tissue samples, was higher than the theoretical error for each of the number of spheres per sample. It is very likely that this discrepancy is caused by the differences in diameter distribution of the various types of microspheres, resulting in non-random error. The smaller spheres tended to go to low flow areas and the larger ones to high flow areas. Because of the non-randomness, the error due to diameter variations in the spheres can be diminished by randomizing the order of injection of the various isotopes. The present study indicates that the relatively high degree of accuracy of the microsphere method for the determination of blood flow to large parts of the myocardium with an unimpeded coronary circulation, as was described in literature, cannot be extrapolated to the determination of regional myocardial blood flow after coronary artery occlusion, when the combination of small tissue samples, variations in the diameter distribution of the spheres and an unevenly distributed myocardial blood flow unfavourably affect the accuracy of the method.

Animals↗
PubMed1992

Clearance of microsphere-entrapped 5-fluorouracil and cytosine arabinoside from the vitreous of primates.

Experiments were conducted with biodegradable microspheres containing antimetabolites to assess the release of the drugs from the microspheres into the vitreous cavity of primates. Microspheres containing a mixture of radiolabeled and cold cytosine arabinoside (Ara-C) or 5-fluorouracil (5-FU) were prepared using a solvent evaporation process. The copolymers of poly (lactic) and poly (glycolic) acid (85:15) and drug was dissolved in a mixture of chloroform and acetone. The solutions were then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. A 0.1 mL aliquot of a suspension of the microspheres was then injected into one eye of eight African Green monkeys. Half received 250 +/- 10 micrograms of Ara-C and the others 375 +/- 15 micrograms of 5-FU. The concentration in the vitreous was then measured by removing a 0.1 mL sample of vitreous at 1, 2, 4 and 11 days after injection. Both drugs released from microspheres were still detectable in the eye 11 days after injection and the clearance kinetics were similar for both drugs. The results indicate that the microspheres appear promising as a slow drug-delivery system for future investigations in conjunction with these and other antimetabolites suitable for the treatment of PVR.

Animals↗
PubMed1979

Aldocyanoin microspheres: partial amino acid analysis of the microparticulates formed from simple reactants under various conditions.

The work of Kenyon and Nissenbaum on aldocyanoin microspheres was repeated and extended. It was determined that the microspheres contained amino acids and that specific amino acids could be incorporated into the microspheres by adding the requisite aldehyde or ketone precursor to the model mixture. Microsphere formation was found to be dependent on the availability of oxygen. Under anaerobic conditions of synthesis, no microspheres formed in the time allotted and the amino acid composition of the macromolecular material was simple. Microparticulate material synthesized by C. Folsome using a quenched spark technique was analyzed and found to contain amino acids that had a qualitative composition similar to both a Miller-Urey discharge and the Kenyon-Nissenbaum microspheres.

Aerobiosis↗
PubMedDate not supplied

The microsphere method facilitates statistical assessment of regional blood flow.

When microspheres are injected into the circulation, they are trapped in the arteriolar or capillary system within various organs. It has been confirmed in animal experiments that the number of microspheres in a myocardial sample approximately follows a Poisson distribution, under adequate experimental conditions. On the basis of this result, we arrived at the following hypothesis: When regional blood flow is measured under a steady state by the reference sample method, the 95% relative error can be approximated by +/- 196 square root 1/v + 1/w, where v and w represent the number of microspheres in blood sample and myocardial sample, respectively. The equation is valid if v and w are greater than 400 and 49, respectively. We obtained an expression of the relation among the percent of increase or decrease in regional blood flow being verified, the probability of increase or decrease, as a statistically significant variation and the number of microspheres in a myocardial sample. An investigator can work out an approximate experimental design using this expression. For instance, when the increase in regional blood flow required for verification is expected to be 20% and he wants this increase to be verified by 90%-probability and as a statistically significant increase, he can predict from this expression that the number of microspheres in a myocardial sample should be 472 and 567 before and after the experimental intervention on the coronary circulation, respectively. The expression is useful as index for experiments involving use of the microsphere method.

Animals↗
PubMed2005

Preparation and in vivo evaluation of huperzine A-loaded PLGA microspheres.

Huperzine A-loaded microspheres composed of poly(D,L-lactide-co-glycolide) were prepared by an ONV emulsion solvent evaporation method. The characterization of the microspheres such as drug loading, size, shape and release profile was described. The in vitro release in the initial 7 days was nearly linear with 10% released per day. Thereafter drug release rate became slow gradually and about 90% drug released at day 21. The in vitro release rate determined by dialysis bag method had a good correlation with the in vivo release rate. Huperzine A aqueous solution was intramuscularly injected (i.m.) at 0.4 mg/kg and microspheres were intramuscularly injected at 8.4 mg eq huperzine A/kg in rats. The maxium plasma concentration (Cmax ) after i.m. microspheres was only 32% of that after i.m. solution. Drug in plasma could be detected until day 14 and about 5% of administered dose was residued at the injection site at day 14. The relative bioavailability of huperzine A microspheres over a period of 14 days was 94.7%. Inhibition of acyecholinesterase activity (AchE) in rat's cortex, hippocampus and striatum could sustain for about 14 days. In conclusion, huperzine A-loaded microspheres possessed a prolonged and complete drug release with significant inhibition of AchE for 2 weeks in rats.

Alkaloids↗
PubMed2004

Controlled release of Bordetella bronchiseptica dermonecrotoxin (BBD) vaccine from BBD-loaded chitosan microspheres in vitro.

Chitosan microspheres were prepared by ionic gelation process with sodium sulfate for nasal vaccine delivery. Bordetella Bronchiseptica Dermonecrotoxin (BBD) as a major virulence factor of a causative agent of atrophic rhinitis (AR) was loaded to the chitosan microspheres for vaccination. Morphology of BBD-loaded chitosan microspheres was observed as spherical shapes. The average particle sizes of the BBD-loaded chitosan microspheres were about 2.69 microm. More BBD was released with an increase of molecular weight of chitosan and with an increase of medium pH in vitro due to weaker intermolecular interaction between chitosan and BBD. Tumor necrosis factor-alpha (TNFalpha) and nitric oxide (NO) from RAW264.7 cells stimulated with BBD-loaded chitosan microspheres were gradually secreted, suggesting that released BBD from chitosan microspheres had immune stimulating activity of AR vaccine.

Animals↗
PubMed1997

Failure in learning task and loss of cortical cholingergic fibers in microsphere-embolized rats.

The present study was undertaken to elucidate the pathological changes in learning and memory functions and in the metabolism of cortical cholinergic neurons following microsphere embolism in the rat. Microspheres (48 microm) were injected into the right internal carotid artery of rats. Learning and memory functions were measured 7 or more days after the embolism by active and passive avoidance, and water maze tasks. In the biochemical study, cortical acetylcholine and choline contents, and choline acetyltransferase activity were measured. Cortical acetylcholinesterase-containing fibers were quantitatively estimated in the embolized rat. The active and passive avoidance, and water maze tasks were impaired in the microsphere-embolized rat. In the histochemical study, the density of cortical acetylcholinesterase-containing fibers of the ipsilateral hemisphere of the microsphere-embolized rat was decreased, but cell density was unchanged. Furthermore, microsphere embolism decreased the cortical acetylcholine concentration and choline acetyltransferase activity and increased the choline concentration. The results suggest that microsphere embolism causes severe damage to cortical cholinergic neurons, which may be, at least in part, related to the impairment of learning and memory functions in the sustained brain ischemia.

Acetylcholine↗
PubMed1999

Holmium-166 poly lactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: effects of preparation and neutron activation techniques.

Since one of the most frequent sites of human metastatic cancer is the liver, particularly in colon and rectum carcinoma, there is a special need for the development of an effective therapy. This study describes the parameters for reproducible production of poly lactic acid (PLA) microspheres with an average diameter of 37 microm and labelled with neutron-activated holmium-166 (Emax=1.84 MeV, t1/2=26. 8 h), suitable for use in internal radionuclide therapy of liver metastases. It is demonstrated that holmium-loaded PLA microspheres can be prepared by a relatively simple method, with incorporation of 17.0%+/-0.6% holmium (n=5), and that 20 GBq can be obtained from 400 mg neutron activatable microspheres. In order to produce this high amount of activity, the microspheres must be free of water and irradiation must be performed in a polyethylene vial, with a relatively low neutron flux (5x10(13) cm-2 s-1) within 1 h. Under these well-defined conditions minor surface changes were seen which barely affected total volume and consequently total radioactivity of the microspheres with a diameter of 20-50 microm. Overall structural integrity was maintained in terms of form and size. In vitro analyses showed that >99.3% of 166Ho activity was retained in the microspheres after 192 h incubation in PBS, plasma and leucocytes, while in liver homogenate retention was still 98.4%.

Brachytherapy↗
PubMed1998

Induction of anti-idiotypic humoral and cellular immune responses by a murine monoclonal antibody recognizing the ovarian carcinoma antigen CA125 encapsulated in biodegradable microspheres.

The use of biodegradable poly(DL-lactic-co-glycolic acid) microspheres as a cancer vaccine delivery system for induction of anti-idiotypic responses was investigated using a murine monoclonal antibody B43.13 that recognizes the human ovarian cancer antigen CA125. Immunization of mice with mAb B43.13 encapsulated in poly(DL-lactic-co-glycolic acid) microspheres resulted in enhanced humoral and cellular immune responses compared with mAb B43.13 alone or mAb B43.13 mixed with microspheres. The antibody responses could be further enhanced by the co-encapsulation of mAb B43.13 with monophosphoryl lipid A, a non-toxic adjuvant, in microspheres. Anti-idiotypic humoral responses were shown to result in Ab2 antibodies mimicking the nominal antigen CA125 and Ab3 antibodies recognizing CA125. Further, microsphere delivery of mAb B43.13 also resulted in induction of T cell responses involving T2 cells reactive with mAb B43.13 epitopes and T3 cells recognizing CA125. These results indicate that microsphere delivery of Abl can induce both humoral and cellular anti-idiotypic responses relevant to cancer antigens. This raises the possibility of the use of such formulations for anti-idiotypic induction immunotherapy for cancer.

Animals↗
PubMed1999

Growth of human fetal retinal pigment epithelium as microspheres.

BACKGROUND: The aim was to develop a three-dimensional cell culture system for human fetal retinal pigment epithelial (HFRPE) cells for in vitro cellular studies and for possible application in subretinal transplantation. METHODS: Pieces of freshly isolated HFRPE monolayer tissue were grown on crosslinked fibrinogen (CLF) films. The growth pattern and morphologic characteristics of the implanted tissue were studied using phase-contrast microscopy, photography, and light and electron microscopy. The cells were screened immunohistochemically for HLA-ABC, HLA-DR, ICAM-1, B7, and Cytokeratin. Cell proliferation was studied using 5-bromo-2-deoxyuridine incorporation. RESULTS: After attachment to CLF, HFRPE monolayer tissue formed small tumor-like formations, i.e. microspheres. HFRPE microspheres survived and proliferated in a floating state for at least 4 months. After attachment of the microspheres to the culture dish floor, formation of a confluent HFRPE cell monolayer with high proliferative activity was noted around the microspheres. HFRPE cells stained positive for HLA-ABC, ICAM-1, and cytokeratin and negative for B7 and HLA-DR. The microspheres could be easily detached from the dish and they were able to initiate similar growth after reattachment. CONCLUSION: HFRPE grown on CLF resemble a three-dimensional culture system with high yield of pure cells that can be useful for a wide variety of in vitro studies. Because of their adjustable size, spherical shape, and ability to initiate growth of cells with a high proliferative potential, HFRPE microspheres may be successfully utilized as a source of donor cells for subretinal transplantation.

B7-1 Antigen↗
PubMed2000

Uptake and degradation of radioactively labelled albumin microspheres as markers for Kupffer cell phagocytosis.

Rats were injected with liposomes containing iodixanol (CTP10 Injection; 100 mg iodine per kg body weight) followed by a second injection of 125I-tyramine-cellobiose-albumin microspheres. The amounts of phagocytosed and degraded labelled albumin in liver were measured. A reduced uptake and degradation of albumin microspheres was observed when the labelled microspheres were injected 2 h or 24 h after the liposomes compared with that obtained in control animals receiving saline. No effect on the uptake and degradation of labelled microspheres was observed when the time lag between the injection of liposomes and labelled microspheres was 1 week. The data show that the uptake and degradation of 125I-tyramine-cellobiose-albumin microspheres can be used as indicators of Kupffer cell phagocytotic function following drug uptake by these cells.

Albumins↗
PubMed2006

Starch-based microspheres produced by emulsion crosslinking with a potential media dependent responsive behavior to be used as drug delivery carriers.

This paper describes the development and characterization of starch microspheres for being used as drug delivery carriers in tissue engineering applications. The developed starch microspheres can be further loaded with specific growth factors and immobilized in scaffolds, or administrated separately with scaffolds. Furthermore and due to the processing conditions used, it is expected that these microspheres can be also used to encapsulate living cells. The aim of this study was to evaluate the efficacy of this methodology for further studies with biologically active agents or living cells. The starch microspheres were prepared using an emulsion crosslinking technique at room temperature to allow for the loading of biologically active agents. A preliminary study was performed to evaluate the incorporation of a model drug (nonsteroidal anti-inflammatory drug-NSAID) and investigate its release profile as function of changes in the medium parameters, such as ionic strength and pH. The developed starch-based drug delivery system has shown to be dependent on the ionic strength of the release medium. From preliminary results, the release seems to be pH-dependent due to the drug solubility. It was found that the developed microspheres and the respective processing route are appropriate for further studies. In fact, and based in the processing conditions and characterization, the developed system present a potential for the loading of different growth factors or even living cells on future studies with these systems for improving bone regeneration in tissue engineering, especially because the crosslinking reaction of the microspheres takes place at room temperature.

Absorption↗