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At least 415 records · Page 23Linked to original sources
PubMed1992

A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: antitumor effect of cis-diamminedichloroplatinum(II) albumin microspheres, containing chitin and treated with chitosan on rabbits with VX2 hepatic tumors.

As an effective therapy for hepatocellular carcinoma, hepatic arterial chemo-embolization therapy has been widely used, and many embolizing materials have been extensively investigated. In the present study, we prepared various types of cis-diamminedichloroplatinum(II) (CDDP) albumin microspheres using chitin and chitosan, both of which have attracted considerable attention as new non-toxic biological polymer materials having favorable characteristics such as immune adjuvant activity, biological compatibility, and biodegradation. Hepatic artery of rabbit hepatic cancer models, which had transplanted VX2 tumors, were embolized with various types of microspheres. The anti-tumor effects and tumor-targeting of the microspheres, and the effects of the microspheres administration on the hepatic tissue were investigated. As a result, anti-tumor activity of the microspheres was increased by the addition of chitin-containing or chitosan treated materials; tumor growth rates of chitin addition and chitosan treated groups were approximately 160% and 120%, respectively, and were significantly lower than that of the non-treatment groups with a rate of approximately 580%. However, complete inhibition of tumor growth might have been impossible. Anti-tumor activity was increased by the addition of chitin-containing or chitosan treated materials. Whereas the growth inhibitory effect was insufficient, in order to potentiate anti-tumor activity, higher CDDP contents and sustained release of CDDP at a high level from microsphere and so on should be essentially improved for the near future. The CDDP level in hepatic tissue following the administration of microspheres was increased by adding chitin to the microspheres or by treating the microspheres with chitosan.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1995

Optimization of preparative conditions for polylactide (PLA) microspheres containing ovalbumin.

Polylactide (PLA) microspheres containing ovalbumin (OVA) as a model protein were prepared by a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. The optimization of preparative parameters for the PLA microspheres containing OVA were performed, and the in vitro characteristics of the obtained microspheres were examined. Firstly, a smaller internal aqueous phase volume was found to be advantageous in obtaining high loading efficiency. Secondly, the addition of 2-10% (w/v) NaCl into the external aqueous phase (0.5% (w/v) polyvinyl alcohol solution) also improved OVA loading efficiency. Prepared products showed a sharp release of OVA at the initial phase, but the following phase was characterized by a slow release rate of OVA that continued at least 28 d. The release rate of OVA from microspheres made of PLA with a molecular weight of 15400 was faster than that from microspheres made of PLA with a molecular weight of 58300. However, the LA/GA (lactide/glycolide) ratio was not likely to have much effect on the release profile of OVA. Finally, the effect of PLA microsphere particle size on the release profiles of OVA was examined. The extent of burst release at the initial phase increased as the mean diameter of prepared PLA microspheres decreased. For example, the PLA microspheres with a small mean diameter (5.0 microns) showed a 40% burst release, but almost 30% of OVA remained in the PLA microspheres (confirmed by HPLC method) after the 28 d release test, suggesting the possibility of using this carrier as a long-acting protein delivery system.

Biocompatible Materials↗
PubMedDate not supplied

Albumin microspheres as delivery systems for photodynamic drugs: physico-chemical studies and their implications for in vivo situations.

The potential of albumin (bovine serum) microspheres as delivery systems for haematoporphyrin and/or its zinc derivative was probed at the molecular level. The microspheres, prepared by heat denaturation, were stable to detergents and organic solvents but could be degraded by proteolytic enzymes. Drug loading was either by encapsulation during microsphere formation or by binding to preformed microspheres. The efficiency of encapsulation was found to depend on the initial drug/protein ratio with a saturable pattern. Binding of both drugs, or each alone, indicated the presence of two types of affinities of each drug to the microspheres. The leakage (release) of drug(s) from the microspheres into the aqueous medium over a period of several hours showed biphasic behaviour for each type of preparation, bound and encapsulated, for one or both drugs. A model assuming the microsphere-bound drug is distributed into two pools, differing in their drug-microsphere affinities, with no interference between the two drugs if both were bound, was found to account well for the equilibria data. Binding constants for respective pools were found to be similar for both drugs, of the order of 0.10 and 2 x 10(-4) ml/micrograms protein for the high and low affinity pools, respectively. The low affinity pools had the higher drug population. The two-pool model also fits well with the kinetic data, the pools differing in the rates of release. Rate constants for both drugs were found to be similar, of the order of 0.3 per min and 0.025 per hour for the fast and slow releasing pools, respectively. The population of the slow-releasing pool was higher, the high-affinity pool being the fast-releasing one, the low-affinity pool being the slow-releasing one. Implications for the microsphere-mediated delivery of these drugs in vivo are discussed.

Drug Carriers↗
PubMedDate not supplied

Preparation, characterization and performance evaluation of neomycin-HSA microspheres.

Human serum albumin microspheres containing neomycin sulphate were prepared using emulsion polymerization and polymer dispersion techniques. The many variables which may affect the shape, size, stability, release of the drug from the microspheres such as internal phase to external phase volume ratio, human serum albumin content, stirring rate, polymer content and stabilizing agent concentration, were studied. Unlike the microspheres prepared by the emulsion polymerization technique, polymer dispersion stabilised microspheres were uniform in size and shape with a narrow range of size distribution. In vitro release of neomycin sulphate from albumin microspheres was studied using the dialysis cell method. The drug release from microspheres followed Q versus (t)-1/2 linear relationship. The in vivo distribution studies on prepared microspheres revealed that the localization takes place preferably in lung tissues, liver, spleen and kidney and is found to be dependent on the microsphere size. On administration of microspheres of 3-6 microns size, approximately 55 per cent of administered drug could be localized in the lungs.

Animals↗
PubMedDate not supplied

Hydroxy-urea bearing albumin microspheres--preparation, characterization and evaluation.

Hydroxy-urea bearing albumin microspheres were prepared using the polymer dispersion method. Glycerol was used successfully in place of water as an internal phase of w/o emulsion, to prepare HSA based albumin microspheres. Silicone coated magnetite of nanometeric size was incorporated in the drug bearing microspheres. The process variables which could affect the physical characteristics with respect to in vitro and in vivo performance of the prepared microspheres were studied. The in vitro release of the drug from the microspheres followed a linear relationship when commulative per cent drug release was plotted against square root of time. Microspheres of average size 1-4 microns were studied for in vivo distribution and localization. It was established that 67 per cent of the drug enveloped in magnetic albumin microspheres could be localized in a rat tail target segment, on applying an external magnetic field of strength 8000 Oe. A remarkable stabilization of hydroxy urea in the prepared microspheres was recorded when t10% drug degradation was compared with the albumin microspheres prepared by a conventional emulsion polymerization method using water as an internal phase.

Animals↗
PubMedDate not supplied

Effect of compression pressure on physical properties and dissolution characteristics of disintegrating tablets of propranolol microspheres.

Propranolol HCl was encapsulated with cellulose acetate butyrate by an emulsion-solvent evaporation method. Three direct compression diluents were blended with appropriate size fractions of the microspheres and each formulation was compressed at several pressures to give tablets that readily disintegrated in water. Tablets with microcrystalline cellulose (MC) as the diluent had the highest tablet crushing strength at any given compression pressure. Heckel plots of all the microsphere-diluent blends were nonlinear, indicating that the consolidation may result from crushing and rearrangement of the individual particles in addition to plastic deformation. Tablet properties and estimated yield pressures showed that MC was the most suitable diluent for compression of propranolol HCl microspheres. Drug release from compressed tablets was always faster than from uncompressed microspheres, but useful sustained-release characteristics were retained. Dissolution tests of MC formulations of the tableted microspheres showed increased release rate constants and decreased 50 per cent dissolution times compared to microspheres that had not been compressed. This result indicated that rupture of some of the microspheres had occurred. The drug release rate increased at higher compression pressures due to the rupture of a greater proportion of microspheres. Larger changes in release rate and t50 percent were observed with larger microspheres sizes. Generally, the least compression pressure that gives tablets with acceptable properties is preferred.

Cellulose↗
PubMedDate not supplied

Changing the pH of the external aqueous phase may modulate protein entrapment and delivery from poly(lactide-co-glycolide) microspheres prepared by a w/o/w solvent evaporation method.

The milk model protein, beta lactoglobulin (BLG), was encapsulated into microspheres prepared by a multiple emulsion/solvent evaporation method. The effect of the pH of the outer aqueous phase on protein encapsulation and release as well as on microsphere morphology has been investigated. At all tested pH values, the encapsulation efficiency was shown to decrease with increasing the initial amount of BLG. This was correlated with the reduced stability of the primary emulsion as the initial BLG increased. In addition, reducing the solubility of BLG in the external aqueous phase by decreasing the pH to the isoelectric point of BLG (pI 5.2) resulted in an improved protein encapsulation. Moreover, it was shown that combining pH modification and optimal stability of the first emulsion yielded microspheres with a high encapsulation efficiency. However, release kinetic studies revealed that a significant burst release was observed with microspheres loaded with large amounts of BLG, especially when prepared in a medium at pH 5.2. This burst effect was attributed to morphology changes in the microsphere surface which was characterized by the presence of pores or channels able to accelerate the release of BLG. These pores were assumed to result from the presence of large amounts of protein molecules on the microsphere surface, that aggregate during microsphere formation at pH 5.2. Indeed, single adsorption experiments have shown that BLG had a higher affinity for the particle surface when the pH was close to the pI. Thus, reducing the solubility of a protein in the external aqueous phase allows the product of microspheres with a better encapsulation efficiency, although this benefit is provided by a strong adsorption of the protein on microsphere surface.

Adsorption↗
PubMed2000

Lectin-mediated bioadhesion: preparation, stability and caco-2 binding of wheat germ agglutinin-functionalized Poly(D,L-lactic-co-glycolic acid)-microspheres.

To take advantage of the cytoadhesive characteristics of Wheat germ agglutinin (WGA) for improved particulate drug delivery, the interaction between WGA-grafted poly(D,L-lactic-co-glycolic acid)-microspheres and Caco-2 monolayers was investigated using bovine serum albumin (BSA) or glycine coated microspheres as a control. Covalent immobilization of WGA by the carbodiimide/N-hydroxysuccinimide-method on 4 microm microspheres yielded a surface density of 9.67+/-1.21x10(6) molecules/particle, whereas 0.22+/-0.04x10(6) WGA-molecules were bound by physical adsorption. After storage for 21 days in HEPES-buffer and treatment of the particles with 5 M urea, 86% of covalently linked lectin was still attached to the particles. At 4 degrees C the Caco-2 binding rate of both, WGA- and BSA-modified particles increased with addition of increasing numbers of particles until saturation was reached at 38150+/-1740 (WGA) or 12066+/-1195 (BSA) microspheres bound/mm(2) Caco-2 monolayer. Inhibition of Caco-2 binding of WGA-functionalized microspheres by chitotriose indicated for specificity of the interaction. As observed by confocal laser scanning microscopy, the fluorescein-loading of the particles was accumulated intracellularly after incubation of Caco-2 monolayers with WGA-modified microspheres contrary to glycine-grafted microspheres. Additionally, in case of WGA-functionalized microspheres the amount of cell associated fluorescein was 200-fold higher than that of the free solution. In conclusion, WGA-modified microspheres are expected to enhance intestinal transport of incorporated drugs due to cytoadhesion provided by the lectin coating.

Animals↗
PubMed2000

Improved nasal bioavailability of FITC-dextran (Mw 4300) from mucoadhesive microspheres in rabbits.

The nasal bioavailability of fluorescein isothiocyanate-dextran (FITC-dextran) (Mw = 4300) encapsulated in non-mucoadhesive and mucoadhesive microspheres in New Zealand White rabbits was investigated. FITC-dextran was administered nasally encapsulated in carbopol 934P, chitosan and lactose microspheres and the bioavailability compared to intravenous administration of FITC-dextran solution. Administration of FITC-dextran as carbopol microspheres produced a significantly greater bioavailability (33%) than after administration as chitosan (13%) and non-mucoadhesive rapidly dissolving control lactose microspheres (9%). The FITC-dextran terminal plasma half-lives after carbopol 934P and chitosan microsphere administration were significantly longer than after intravenous administration of FITC-dextran. The FITC-dextran terminal plasma half-life after carbopol 934P microspheres administration was significantly longer than after lactose microsphere administration. This data suggested that the increase in FITC-dextran bioavailability after carbopol 934P microspheres administration was due to increased residence at the absorptive site via mucoadhesion and reduced mucociliary clearance. A change in mucosal permeability could not however be discounted especially for the chitosan microspheres.

Animals↗
PubMed1998

Effect of polytyrosine on the hydrophobicity of hydroxyethyl starch microspheres.

The polypeptide, poly-l-tyrosine (PTYR) was incorporated into hydroxyethyl starch (HES) microspheres to modify the surface hydrophobicity in order to allow subsequent radioiodination and assessment of uptake into the intestinal mucosa following oral administration. The HES microspheres were prepared by a crosslinking polymerization process and characterized for particle size, peptide content and surface morphology. The hydrophobicity of the characterized microspheres was assessed by two techniques-water uptake (swelling) of the microspheres and contact angle measurement using the sessile drop method. Spherical microspheres containing PTYR were prepared with a greater than 80% loading efficiency in the 1-10 microns size range. The surface morphology suggested localization of the PTYR at the surface proportionate to the loading. The percent water uptake of the blank HES microspheres was 87%, whereas that of the 5, 10 and 20% PTYR/HES microspheres was 84%, 61% and 55%, respectively. HES/PTYR was polymerized as films to facilitate contact angle measurement. A monotonical increase in the contact angle was observed as the concentration of the PTYR was increased to 20%. Contact angle of pure HES (0% PTYR) films was 16 degrees and for the PTYR-containing films was 29 degrees for 5% PTYR, 39 degrees for 10% and 57 degrees for 20%. The hydrophobicity of the HES microsphere system could be increased by the incorporation of polytyrosine thereby paving the way to radioiodinate the microspheres and perform uptake studies in an animal model.

Hydroxyethyl Starch Derivatives↗
PubMed2002

Injection of chemotherapeutic microspheres and glioma. IV: Eradicating tumors in rats.

Polymer microspheres can be easily injected into the brain to provide a local and sustained delivery of chemotherapeutics to a tumor or surrounding tissue subject to high rates of tumor recurrence following surgery. Building on previous studies that established the clear advantage of local, peritumoral injections of sustained release microspheres, the following experiments utilized two different approaches for maximizing the survival benefit in glioma-bearing rats. In the first experiment, a previously grown cortical tumor was debulked and animals received either one or two treatments with carboplatin-loaded microspheres (either 200 or 800 microg total carboplatin per treatment). In each case, the microspheres were injected along the perimeter of the resection cavity with each treatment separated by 20 days. Survival studies clearly demonstrated that two, temporally spaced injections were superior to a single series of injections. At the lowest dose tested (200 microg), median survival was increased an additional 40% over that in animals receiving one treatment. At the higher dose (800 microg), one third of the animals receiving two separate treatments were long-term survivors (> 150 days) and showed complete eradication of the tumor on histological examination. In the second experiment, we directly compared the efficacy produced by sustained release carboplatin or 1,3-bis[2-chloroethyl]-1-nitrourea (BCNU) alone versus injecting carboplatin and BCNU-loaded microspheres blended together as a single suspension. Carboplatin and BCNU both enhanced survival, with BCNU being significantly less effective than carboplatin. However, the greatest improvements in survival were seen when a blended suspension of carboplatin and BCNU microspheres was injected around the surgical cavity. In contrast, spatially alternating injections of BCNU and carboplatin microspheres was significantly less effective and the increase in survival was no greater than that achieved with BCNU alone. These data offer further support for the potential utility of local, sustained release chemotherapeutic microspheres for treating glioma. Moreover, they suggest that injectable chemotherapeutic microspheres may offer important advantages by (a) permitting multiple, temporally spaced injections to be made, as needed, and (b) providing the opportunity to deliver combinations of several different efficacious drugs directly to the tumor site to enhance survival beyond what can be achieved with delivery of any single chemotherapeutic agent.

Animals↗
PubMedDate not supplied

Viscosity of polymer solution phase and other factors controlling the dissolution of theophylline microspheres prepared by the emulsion solvent evaporation method.

The objectives of this investigation are to evaluate the effect of the viscosity of polymer solution phase on microsphere properties, especially the drug release characteristics since no studies on this formulation variable have been reported. Also, since it is known that polymer molecular weight affects both the viscosity of the polymer solution and the release properties of microspheres, the interaction of these factors was studied. Microspheres with 33% theoretical drug loading of anhydrous theophylline core material were prepared by the emulsion solvent evaporation method. Two cellulose acetate butyrate polymers, (CAB381-2, CAB381-20), chemically similar but having different molecular weights, were used to prepare different polymer solutions having different apparent viscosities in acetone. A Brookfield viscometer was used to evaluate the viscosities of polymer solutions. Dissolution rates of microspheres prepared from the polymer solutions were inversely related to the initial polymer solution viscosities for both CAB381-2 and CAB381-20. The times for the release of 30 and 50% of the drug from the microspheres have a linear relationship with initial polymer solution viscosity. Initial release was significantly decreased with increasing polymer solution viscosity. Unlike CAB381-2 microspheres which follow Higuchi spherical matrix release kinetics, microspheres prepared from the higher molecular weight polymer (CAB381-20) showed extended release dissolution profiles with near zero order kinetics. It is evident that both the polymer solution viscosity and the molecular weight have an effect on the drug release from microspheres. These results suggest that release rates of matrix microspheres could be predictably optimized by adjusting the viscosity of polymer solutions.

Delayed-Action Preparations↗
PubMedDate not supplied

Formulation and in vitro/in vivo evaluation of terbutaline sulphate incorporated in PLGA (25/75) and L-PLA microspheres.

Terbutaline sulphate (TBS) is widely used in the treatment of bronchial asthma, chronic bronchitis and emphysema. Because of its short biological half life and dosing schedule, a long acting TBS formulation is required to improve patient compliance. The objective of this study was to develop a TBS containing biodegradable microsphere formulation. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactic acid) (L-PLA) were chosen as matrix materials. A solvent evaporation method was used for preparation of microspheres. Surface morphology, particle size distribution and encapsulation efficiency were investigated. In vitro release studies were performed in pH 7.4 phosphate buffer. In vitro distribution of microspheres were studied in the Swiss albino male mice. All microspheres were spherical in shape and had a porous surface with mean diameters of 9-21 microm. The encapsulation efficiency was influenced by the polymer type, but not the molecular weight. About 90% of the initial amount was trapped in PLGA microspheres, and the remainder was on the surface. In the case of L-PLA, 50% of the total drug was associated with the surface of microspheres. The In vitro release pattern was biphasic characterized by an initial burst phase followed by a slower phase. The L-PLA microspheres released approximately 92% of the initial payload in 72 h. On the other hand, TBS release was increased with an increase in the molecular weight of PLGA. Biodistribution of L-PLA microspheres was characterized by an initially high uptake (35%) by the lungs. All these results suggest that L-PLA and PLGA microspheres have the potential to be used for passive lung targeting.

Biodegradation, Environmental↗
PubMed2006

[Preparation of uniform-sized chitosan microspheres and application as carriers for protein drugs].

Chitosan microsphere has been wildly researched in controlled release of protein and peptide drug because of its excellent mucoadhesive and permeation enhancing effect across the biological surfaces. The control of the size and size distribution of microspheres is necessary in order to improve reproducibility, bioavailability, and repeatable release behavior. In this work, uniform-sized chitosan microspheres containing insulin were prepared by a novel membrane emulsification technique combined with glutaraldehyde crosslinking method. In order to prepare uniform-sized chitosn microspheres, it is necessary to modify hydrophilic membrane into hydrophobicity. It is found that there exists a linear relationship between the size of chitosan microspheres and pore size of the membrane used, so it is easy to control the size of microspheres by using membranes with different pore size. In this study, the effect of different amount of crosslinker and crosslinking time on microspheres' morphology, encapsulation efficiency (EE) and release profile of drug in vitro were investigated. It is shown that the morphology of microspheres is more smooth and spherical, and the release rate is slower with the increase of amount of glutaraldehyde and prolongation of crosslinking time. When the molar ratio of amino group of chitosan to aldehyde group of glutaraldehyde is 1:0.7, and crosslinking time is 1 h, the highest EE was obtained (about 65%). Date obtained suggest that chitosan microspheres prepared by this new method would be a promising system for controlled release of protein drugs.

Biocompatible Materials↗
PubMed2006

[Efficacy of 5-fluorouracil polyactic acid microsphere in prevention of proliferative vitreoretinopathy].

OBJECTIVE: To evaluate the efficacy of 5-fluorouracil polyactic acid microsphere in prevention of proliferative vitreoretinopathy (PVR). METHODS: 5-fluorouracil polyactic acid microsphere or 5-fluorouracil were used to implant into rabbits vitreous cavity. 48 healthy rabbits were divided into 3 groups: rabbits in Group 1 received implantation of 5-fluorouracil polyactic acid microsphere; rabbits Group 2 served as polyactic acid microsphere control; rabbits in Group 3 received only 5-fluorouracil powder. Macrophages were injected into vitreous cavity of rabbit to induce PVR. 0.2 ml BSS containing 25 mg microsphere with 2.6 mg 5-fluorouracil was injected into vitreous cavity of two eyes in Group 1. 0.2 ml BSS containing 25 mg microsphere without medicine and 0.2 ml BSS containing 2.6 mg 5-fluorouracil were injected into rabbits vitreous cavity in Group 2 and 3 respectively, Drug content in aqueous humor was measured regularly. Release feature of 5-fluorouracil polyactic acid microsphere in vivo was observed. The efficacy of the inhibition of PVR was evaluated according to Ryan's grade of proliferative vitreoretinopathy. RESULTS: The releasing time of 5-fluorouracil polyactic acid microsphere was much longer than 5-fluorouracil powder. Its half life T(1/2) was 379.05 h with low clearance rate. The attack rate of retinal detachment in Group 2 was 62.5% and 71.9% on the 21st and 28th day respectively. The attack rate of retinal detachment in Group 3 was 64.3% and 78.6% whereas that of Group 1 was 13.3% and 13.3% on the 21st and 28th day. There was statistical difference in retinal detachment rate in Group 1 and 2 or 3 (P < 0.01). No differences was found in retinal detachment ration in Group 2 and 3 (P > 0.05). CONCLUSION: Implantation of 5-fluorouracil polyactic acid microsphere into vitreous cavity can effectively prevent proliferative vitreoretinopathy induced by macrophages in rabbit model.

Animals↗
PubMed2006

[Effect of preparation technique on in vitro release mechanism of huperzine A microspheres].

AIM: To investigate the effect of preparation technique on in vitro release mechanism of huperzine A-PLGA microspheres. METHODS: Huperzine A-PLGA microspheres were prepared by two kinds of O/O emulsion solvent evaporation method (method A and B). In vitro release mechanism was explained by release profile, degradation rate and swelling rate of microspheres in vitro. The microspheres morphology and drug distribution within microspheres were observed in order to explain further the drug release mechanism. RESULTS: The encapsulation efficiency of huperzine A microspheres prepared by method A and B was 47.60% and 83.50% respectively. Microspheres prepared by method A could sustain release for 35 days with nearly no initial burst release. The release profile fitted well to zero order equation and drug release mainly through degradation and diffusion mechanism. Huperzine A microspheres prepared by method B could sustain release for 21 days with some evidence of initial burst release. The release profile fitted well to the Higuchi equation and drug release was mainly through diffusion mechanism. CONCLUSION: Huperzine A microspheres prepared by method A had more desirable release profile.

Alkaloids↗
PubMed1994

Cell surface distribution of high-avidity LFA-1 detected by soluble ICAM-1-coated microspheres.

Murine recombinant soluble ICAM-1 (sICAM-1) was immobilized on polystyrene microspheres. The binding of sICAM-1-coated microspheres to splenic T cells required previous activation of the cells and was inhibited by antibody to LFA-1 (CD11a/CD18), indicating that sICAM-1-coated microspheres bind exclusively to high-avidity LFA-1. The cytoskeleton inhibitor cytochalasin B did not inhibit the binding of sICAM-1-coated microspheres to PMA-activated splenic T cells, whereas their adhesion to sICAM-1 immobilized on microtiter wells was almost completely inhibited. The murine T hybridoma T28 cells on activation with PMA also bound sICAM-1-coated microspheres, and the binding sites on the cell surface seemed localized on some of the cells, whereas fluorescence staining showed an even distribution of LFA-1 on the cell surface. In contrast, the murine B cell line A20A8 and monocytic line P388 showed a more even distribution of sICAM-1 binding sites. To further investigate the distribution of high-avidity LFA-1, murine fibroblast L cells expressing LFA-1 were generated by gene transfer. The transfected L cells constitutively expressed high-avidity LFA-1 and bound sICAM-1-coated microspheres without previous activation. Interestingly, the binding sites seemed highly localized on most cells. In contrast, the binding sites for anti-LFA-1 Ab-coated microspheres were randomly distributed on the transfected L cells. Furthermore, fluorescence staining also revealed a uniform punctate distribution of LFA-1 on the surfaces of these cells. These results show that 1) sICAM-1-coated microspheres represent a useful tool in identifying high-avidity LFA-1, 2) the binding of sICAM-1-coated microspheres to high-avidity LFA-1 does not require an intact cytoskeleton, and 3) the cell surface distribution of high-avidity LFA-1 can be different from that of LFA-1 in general, and the former seems highly localized on some cells.

Animals↗
PubMed1993

[Study on compound levonorgestrel microspheres].

Levonorgestrel (LNG) and estradiol (E2) were mixed in the ratio of 5:2 by weight. Compound LNG gelatin-microspheres were prepared by phase-separation method, natural biodegradable gelatin being used as the core material. The experimental conditions were optimized, the mean diameter of the microspheres obtained being 10-40 microns, and the rate of encapsulation 65-75%. Storage observations and acceleration tests of the compound LNG gelatin-microsphere injection prepared showed that the microspheres have good stability. The thermal degradation activation energy of the injection was determined to be 134.4 kJ/mol, based on differential scanning colorimetry (DSC). T1/2 values for dissolution in vitro of LNG and E2 from the compound LNG gelatin-microsphere injection and from the unencapsulated injection showed significant difference (P < 0.01), indicating that the microspheres have good sustained release action. Effects of the pure LNG microsphere injection and compound LNG microsphere injection on the mouse ovary were compared histologically. The results showed that the compound LNG microsphere injection reduced some of the side effects such as ovary congestion. This points out that the compound dosage form can clinically alleviate the irregular bleeding caused by the administration of LNG alone.

Animals↗