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At least 523 records · Page 29Linked to original sources
PubMed1991

Photosensitized destruction of human bladder carcinoma cells treated with chlorin e6-conjugated microspheres.

A photosensitizer conjugate, chlorin e6 (Ce6) covalently bound to 1-micron-diameter polystyrene microspheres, has been investigated in the photodynamic destruction of MGH-U1 human bladder carcinoma cells in vitro. The microspheres were taken up avidly by the carcinoma cells; confocal laser scanning fluorescence microscopy showed them to be localized in the cytoplasm, apparently within lysosomes, visualized by labeling with acridine orange. In contrast, fluorescence of unconjugated Ce6 was present within most cellular membranes. Use of Ce6-microsphere conjugates led to a 20-fold-higher mean intracellular concentration, compared with unconjugated Ce6. Cells incubated in the presence of Ce6-microsphere conjugates (0.43 microM equivalent) and subsequently irradiated at 659 nm with a dye laser pumped by an argon-ion laser showed dose-dependent phototoxicity, leading to total inhibition of colony formation at a radiant exposure of 5J/cm2; in contrast, cells incubated with either unconjugated Ce6 (0.43 microM) or unconjugated microspheres before laser irradiation were unaffected. Cells pretreated with Ce6-microsphere conjugates and irradiated in the presence of 90% 2H2O showed significantly increased phototoxicity, an effect consistent with an important role for excited-state singlet oxygen in the mechanism of injury. In solution, however, photosensitized generation of singlet oxygen with Ce6-microsphere conjugates was 9 times less efficient than with unconjugated Ce6. The markedly greater phototoxicity of Ce6-microsphere conjugates compared to unconjugated Ce6 was therefore a consequence of the high intracellular Ce6 concentration attained by phagocytosis of the conjugates and their particular sites of intracellular localization. Thus, these conjugates are an efficient system for the delivery of photosensitizing drugs to carcinoma cells.

Cell Division↗
PubMedDate not supplied

Characterization of drug release from diltiazem-loaded polylactide microspheres prepared using sodium caseinate and whey protein as emulsifying agents.

The influence of milk protein emulsifying agents on the characteristics, particularly drug release, of polylactide microspheres was investigated. Diltiazem loaded polylactide (PL) microspheres were successfully prepared using the dairy proteins, sodium casinate (SC) and whey protein isolate (WPI) as the emulsifying agents. Microspheres were characerized in terms of microsphere yield, electron microscopy, particle size, drug loading, DSC and XRD analysis and drug release. The yields of microspheres obtained were 53-63% and were independent of the emulsifying agent used. SEM revealed that, regardless of the emulsifying agent employed, the microspheres were of good sphericity, but the surface appearance of the microspheres was not the same in all cases. The milk proteins resulted in microspheres approximately half the size of those obtained with methylcellulose (MC). Significant differences in drug loading were observed between the three emulgents, the MC systems giving the highest values. Release profiles were sigmoidal in shape and were well fitted to the equation ln (x/1 - x) = k x t - k x tmax, reflecting degradation controlled drug release. The parameter k increased with drug loading, while tmax decreased. The relationships between the release parameters [P(k and tmax)] and loading (L) could be quantified by equations of the form P = a x L(N), N being negative in the case of tmax. Apart from the effect on loading efficiency, neither SC nor WPI appeared to significantly alter drug release. The quantitative relationships observed in this study may have more general application in quantifying drug release from drug-polymer composites at low loadings where polymer degradation controls drug release.

Calorimetry, Differential Scanning↗
PubMedDate not supplied

Effects of the characteristics of chitosan on controlling drug release of chitosan coated PLLA microspheres.

Chitosan has been shown to be a biomaterial with good biocompatibility, and is highly biodegradable. This study investigated the effect of post-coating PLLA microspheres with different chitosans on the initial burst and controlling the drug release of the microspheres. Without chitosan, 19.2% of encapsulated lidocaine would release from PLLA microspheres within the first hour (R1), and the time of 50% release (T50) was 25 h. After the microspheres were coated with chitosan of viscosity (eta) 384 +/- 10cp, R1 and T50 could be reduced and prolonged to 14.6% and 90 h, respectively, for all tested molecular weights (Mw) of chitosan. In the case of the same Mw of chitosan being applied, the efficacy of reducing the initial burst of drug release was higher for a lower degree of deacetylation (D.D.). With chitosan in acetic acid solution, coating the microspheres with high Mw and high viscosity could most effectively reduce the initial burst and control drug release of PLLA microspheres. For example, the microspheres coated with chitosan solution of Mw 800 kDa and eta of 1479 cp, R1 and T50 could be reduced and prolonged to 7.4% and 245 h, respectively. The study indicated that manipulating the viscosity of the chitosan solution was the most important factor in contributing to controlling the drug release of chitosan post-coated PLLA microspheres.

Chitin↗
PubMedDate not supplied

The in-vitro and in-vivo characterization of PLGA:L-PLA microspheres containing dexamethasone sodium phosphate.

Dexamethasone sodium phosphate (DSP) is a widely used corticosteroid in the treatment of brain oedema associated with brain tumours. DSP has many side effects that limit its usage at an effective concentration. The objective of this study was to minimize these side effects by encapsulating DSP using biodegradable synthetic polymers, to extend the release time from microspheres and to evaluate the effectiveness in the treatment of brain oedema. Microspheres containing 5% DSP were formulated by the solvent evaporation method by using a 1:1 mixture of two synthetic polymers, poly(lactic-co-glycolic acid) and L-polylactic acid (PLGA and L-PLA). The surface morphologies and particle size distribution of the microspheres were investigated. The in-vitro release studies were performed in pH 7.4 phosphate buffer solution. For determining the effectiveness of microspheres in the treatment of brain oedema, Sprague-Dawley rats weighing 200-250g were used as an animal model. Brain oedema was generated by the cold lesion method, and the effectiveness of the microspheres in treatment of oedema was investigated by the wet-dry weight method, lipid peroxidation ratios and histological evaluations. The average particle size of the microspheres was 13.04 +/- 2.05 microm, and the in-vitro release time of the microspheres was 8 h for 100/release. The degree of oedema was significantly different from the control group for the wet-dry weight method and lipid peroxidation ratio (p < 0.05). Similarly, histological evaluation of the tissues shoved that degree of oedema was significantly decreased with respect to the control group. All these results showed that implantation of microspheres was significantly more effective with respect to the systemic administration of DSP.

Animals↗
PubMedDate not supplied

Effects of inner water volume on the peculiar surface morphology of microspheres fabricated by double emulsion technique.

Poly(D,L-lactide-co-glycolide) (PLG, 65:35) was used to encapsulate bovine serum albumin (BSA) using a water-in-oil-in-water (W/O/W) double emulsion solvent extraction technique. To investigate the effects of an inner water/oil ratio on microsphere characteristics, microspheres were fabricated using four different formulations with a fixed oil volume of 12ml and the inner aqueous phase volume of 0.2ml, 0.3 ml, 0.4ml or 0.5 ml, respectively. Spherical microspheres were obtained after collection by filtration for formulations employing any of the four different inner water/oil ratios. However, microspheres with smaller inner water volumes tend to collapse after vacuum drying. The surface of the formulation with a higher inner water/oil ratio was shown to possess many more pores than that of the formulations with lower inner water/oil ratios. These pores may facilitate the water withdrawal during vacuum drying. Furthermore, microspheres with the lowest inner water/oil ratio (1/60) had higher initial burst release due to its larger surface area. However, microspheres with the highest inner water volume yield a faster release profile of BSA due to interconnected voids within microspheres and more pores on the surface. Therefore, the inner water/oil ratio is a crucial factor in the W/O/W double emulsion technique affecting the morphology and release kinetics of the resulting microspheres.

Drug Delivery Systems↗
PubMedDate not supplied

Preparation, characterization and in vitro drug release of isosorbide dinitrate microspheres.

Microspheres of isosorbide dinitrate (ISDN) were prepared using the emulsification/solvent evaporation method. The impacts of different factors such as stirring rate, concentration of ethyl cellulose (EC) as matrix polymer, poly vinyl chloride (PVA) as stabiliser and ISDN on the characteristics of the microspheres were investigated. The morphology of microspheres was studied using optical and scanning electron microscopy and it was shown that microspheres had a spherical shape and smooth surface. The particle size distribution of microspheres, analysed by a sieving method, was affected by stirring rate and concentrations of EC, PVA and ISDN. Larger microspheres showed greater drug loading and smaller microspheres showed a faster drug release. The in vitro drug release from microspheres was predictable and reproducible, conforming to the Higuchi model of release kinetics.

Cellulose↗
PubMedDate not supplied

Gastro-resistant microspheres containing ketoprofen.

Ketoprofen gastroresistant microspheres were prepared by spray-drying using common pH dependent polymers, such as Eudragit S and L, CAP, CAT and HPMCP. The long ketoprofen recrystallization time was a serious hindrance to the preparation of microspheres having a drug content higher than 35%. Microspheres were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffractometry and in vitro dissolution studies, and used for the preparation of tablets. During this step, the compaction ability of the spray-dried powders was measured. While the compressibility of the microspheres containing the enteric cellulosic derivatives are not acceptable and different from those of the microcrystalline cellulose, the compaction properties of ketoprofen/Eudragit L or S microspheres are comparable to those of the Avicel PH 101. In vitro dissolution studies were performed on the microspheres and the tablets. All microspheres showed a good gastroresistance, but some differences among the five polymers in reducing drug release at low pH values are present. Acrylic polymers (Eudragit L or S) are considerably more effective than the cellulosic derivatives CAP and CAT, while the HPMCP profile is in an intermediate position. These differences are erased by the microspheres compression process. In HCl 0.1 N, the percentage of ketoprofen released from the tablets is always close to zero, independently from the polymer used.

Acrylates↗
PubMedDate not supplied

Solvent, emulsifier and drug concentration factors in poly(D,L-lactic acid) microspheres containing hexamethylmelamine.

Biodegradable poly(D,L-lactic acid) (PLA) microspheres containing hexamethylmelamine (HMM) were developed for potential use in chemoembolization and intraperitoneal implantation. The emulsion-solvent-evaporation/extraction method was used to prepare 15 formulations with different drug/polymer ratios, solvent compositions and emulsifer concentrations in the continuous aqueous phase. A central composite experimental design was used, with five levels of the three different factors. All formulations resulted in the formation of discrete matrix microspheres containing crystalline drug. The mean particle sizes of the microsphere formulations ranged from 62-348 microm and the effect of the independent variables on microsphere size was satisfactorily predicted using response surface methodology. For theoretical drug loads of 5-40%, efficiency of entrapment ranged from 75-107% and porosities of the microspheres were between 0-6.5%. The rate of drug release from the microspheres depended on drug loading and particle size. Microspheres with 22.5% or greater theoretical drug content released drug rapidly, with almost complete release occurring in 70 h or less. Formulations with drug loading of 5% and 9.57%, however, released drug very slowly, with less than 50% released in 40 days. Release kinetics of narrow sieve cuts of microspheres with high drug load (35.4%) followed square root of time profiles.

Altretamine↗
PubMedDate not supplied

Effects of solvent evaporation rate on the properties of protein-loaded PLLA and PDLLA microspheres fabricated by emulsion-solvent evaporation process.

This paper investigated the effects of the rate of solvent removal by varying the ambient pressure at a fixed temperature on the morphology, particle size, encapsulation efficiency and release pattern of albumin-loaded PLLA and PDLLA microspheres, prepared by the W/O/W emulsion-solvent evaporation process. For PLLA microspheres prepared either with a fast rate of solvent evaporation (FRSE) or a normal rate of solvent evaporation (NRSE) process, the difference in morphology was minor. In contrast, the different processes did affect the morphology of PDLLA microspheres. Large (surface) pores were observed for PDLLA microspheres fabricated with a FRSE process, while a smooth surface was seen in those with a NRSE process. With the FRSE process, both PLLA and PDLLA microspheres showed smaller particle sizes and lower albumin encapsulation efficiencies than those prepared in the NRSE process. PLLA microspheres prepared with the NRSE process had higher drug encapsulation efficiencies than PDLLA ones, but this was not the case for the FRSE process. An initial burst release of albumin was observed for both PLLA and PDLLA microspheres prepared with the NRSE process, while a lesser burst release was seen for those prepared with the FRSE process. In subsequent stages of drug release, PLLA microspheres prepared with the two different processes showed differences, but this was not the case for PDLLA ones.

Albumins↗
PubMedDate not supplied

Characterization of FITC-albumin encapsulated poly(DL-lactide-co-glycolide) microspheres and its release characteristics.

In this study, the fluorescein isothiocyanate (FITC)-albumin distribution, the amount of FITC-albumin release and the degradation of poly (DL-lactic-co-glycolic acid) (PLGA) microspheres were evaluated. The higher the FITC-albumin concentration in the W1 phase, the higher the protein concentration and loading efficiency in the microspheres, the larger the particle size of microspheres. Confocal laser scanning microscopy (CLSM) showed that the FITC-albumin was distributed uniformly in the microspheres with a low concentration while it was aggregated at higher concentrations. The high protein concentration in the microspheres showed significantly large initial release (above 70% w/w) during the 10 days. A higher PVA concentration in the W2 phase resulted in a smaller particle size, higher protein contents and loading efficiency and decreased release rate. After a 10 day incubation period, the microspheres with a low FITC-albumin concentration had an almost spherical morphology, while microspheres with a high FITC-albumin concentration had a more distorted morphology, suggesting that rapid morphological changes and microspheres ruptures can be induced by an initial burst release.

Biocompatible Materials↗
PubMed2004

Preparation of polysulfone hollow microspheres encapsulating DNA and their functional utilization.

Polysulfone hollow microspheres encapsulating DNA were prepared using a liquid-liquid phase separation technique. The microspheres were then used to absorb a DNA-binding intercalating material--ethidium bromide. The amount of DNA encapsulated in the microspheres depended on the concentration of the DNA solution used to prepare the microspheres, and the microsphere morphology depended on both the polymer concentration and the preparation conditions. The amount of ethidium bromide in the microspheres depended mainly on the amount of encapsulated DNA, and the microsphere morphology also affected the removal of the ethidium bromide. The new method of DNA encapsulation is proposed, and the microspheres encapsulating the DNA have the potential to be used in environmental applications.

Animals↗
PubMed2004

An improvement of double emulsion technique for preparing bovine serum albumin-loaded PLGA microspheres.

A modified double emulsion technique was adopted to prepare bovine serum albumin (BSA) loaded poly (D,L-lactic-co-glycolic acid) (PLGA) microspheres. In the formulations, polysorbates (Tween) such as Tween20, Tween40 or Tween80, instead of frequently used poly (vinyl alcohol) (PVA), was used as the emulsifier. Microspheres with porous surface, large particle size, low microsphere yield (approximately 65.4%) and BSA entrapment efficiency (approximately 25.2%) were obtained when Tween80 aqueous solution alone was used as the outer aqueous phase. However, microspheres with smooth surface, high yield and BSA entrapment efficiency could be produced successfully by introducing sodium chloride or glucose into the outer aqueous phase. Adding 5.0%(w/v) sodium chloride into the continuous phase led to increase in microsphere yield and BSA entrapment efficiency from 65.4% and 25.2% to approximately 100% and 76.6%, respectively. Microsphere yield and BSA entrapment efficiency increased from 64.5% and 25.2% to 97.2% and 89.3%, respectively, when 15.0%,(w/v) glucose was added into the continuous phase. In constrast to the microspheres prepared in the presence of additive, a more marked burst release was observed for microspheres prepared without additive in the continuous phase, which may be attributed to the porous morphology of the latter.

Animals↗
PubMed2004

Nasal delivery of insulin using chitosan microspheres.

Nasal delivery of insulin is an alternative route for administration of this drug. The objective of this study was preparation of chitosan microspheres for insulin nasal delivery. After preparation of insulin chitosan microspheres by emulsification-cross linking process, the effect of chitosan quantity (200-400mg), cross-linker type (ascorbic acid or ascorbyl palmitate) and amount (70-140 mg) were studied on the morphology, particle size, loading efficiency, flow and release of insulin from the microspheres by a factorial design. Optimized formulation was administered nasally in four groups of diabetic rats and their serum insulin levels were analysed by the insulin enzyme immunoassay kit and the serum glucose by the glucose oxidase kits. Insulin loading in microspheres was between 4.7-6.4% w/w, preparation efficiency more than 65% and mean particle size was 20-45 microm. In most cases, drug released followed a Higuchi model. Ascorbic acid caused an increase in stability, particle size and T50%, while decreased the loading efficiency and production efficiency. Increasing the chitosan content, increased particle size, flow and insulin release rate form the microspheres. The increase of cross-linking percentage decreased the flow and size of the microspheres while increase of cross-linking percentage promoted the stability and decreased DE8% of insulin. Microspheres containing 400mg of chitosan and 70mg ascorbyl palmitate caused a 67% reduction of blood glucose compared to i.v. route and absolute bioavaliability of insulin was 44%. The results showed that chitosan microspheres of insulin are absorbable from nasal route.

Administration, Intranasal↗
PubMed2005

Optimizing double emulsion process to decrease the burst release of protein from biodegradable polymer microspheres.

The process parameters such as the compositions of inner and outer aqueous phase and emulsification technique of the primary emulsion were optimized to decrease the burst release of BSA from biodegradable polymer microspheres in double emulsion method. It was found that diminished burst release of -14% was achieved for the microspheres produced by formulations, where no phosphate was present in the inner water phase (non-buffered system). Primary emulsion made by probe sonication rather than homogenization or mechanical stirring led to microspheres with insignificant burst effect. Microspheres obtained using 0.1% aqueous Tween 80 solution as the outer aqueous phase, frequently exhibit reduced burst effect of 2.7%. Low microsphere yield (52.1%), however, was observed. Microsphere yield was, therefore, enhanced by addition of additive such as sodium chloride, glucose or mannitol into the outer aqueous phase. Decrease in BSA entrapment was observed in the presence of sodium chloride, but reduction in entrapment efficiency was observed in the case of glucose. Burst release increased from 2.7% to 9.5% or 3.4% as 2.5% sodium chloride or 7.5% glucose was added into the outer aqueous phase respectively. Marked burst release (>20%) was observed in the presence of additive of higher concentration independent of sodium chloride or glucose. As far as surfactant type was concerned, diminished burst was found when PVP or Tween 80 rather than PVA was utilized as the surfactant during microsphere preparation. In addition to PLGA, the copolymers of L-lactide (LLA) and dimethyl trimethylene carbonate (DTC) or trimethylene carbonate (TMC) were also evaluated. Insignificant burst effect was found for the microspheres composed of DTC or TMC copolymers.

Animals↗
PubMed2006

Preparation and evaluation of Eudragit S 100 microspheres as pH-sensitive release preparations for piroxicam and theophylline using the emulsion-solvent evaporation method.

Microencapsulation of the anti-inflammatory drug piroxicam and the anti-asthmatic drug theophylline was investigated as a means of controlling drug release and minimizing or eliminating local side effects. Microspheres of both drugs that are different in the chemical nature and size were successfully encapsulated at a theoretical loading of 25% with the pH sensitive Eudragit S 100 polymer using the emulsion-solvent evaporation method. Solvent composition, stirring rate and the volume of the external phase were adjusted to obtain reproducible, uniform and spherical microspheres. The size distribution of microsphere batches generally ranged from 125-500 microm with geometric means close to 300 microm. Optical light microscopy was used to identify the microsphere shape. Drug loading was determined by completely dissolving the microspheres in an alkaline borate buffer at pH 10. In vitro dissolution studies were carried out on the microspheres at 37 degrees C (+/-0.5 degrees C) at 100 rpm with USP Dissolution Apparatus II using the procedure for enteric-coated products at two successive different pH media (1.2 and 6.5). Both preparations exhibited an initial rapid release in the acidic medium with theophylline showing a larger increase in the amount released during this stage. The drug release was sustained for both preparations at pH 6.5 with theophylline microspheres, showing more extended release. Drug release rate kinetics followed a Higuchi spherical matrix model for both microsphere preparations.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

Modification of the initial release of a highly water-soluble drug from ethyl cellulose microspheres.

The aim of this study was to develop a microspherical dosage form for a highly water-soluble drug, fenoterol HBr, by using the water insoluble, non-biodegradable polymer, ethyl cellulose. Fenoterol HBr was used as a model drug, based on its pharmacokinetic properties, i.e. the short half-life, incomplete absorption from the gastrointestinal tract due to the first pass effect. Three factors, the initial amount of drug, the volume of non-solvent (petroleum benzin) and the stirring speed of homogenizer, were varied during microsphere preparation. The release of fenoterol HBr from these microparticulate delivery systems was compared, and a possible release mechanism was proposed. The encapsulation efficiency of the drug, the morphology and the particle size of the microspheres were also investigated. The oil-in-oil solvent evaporation method efficiently encapsulated fenoterol HBr in these ethyl cellulose microspheres. A significant increase in the encapsulation efficiency of fenoterol was observed when the drug/polymer ratio was decreased from 15% to 5% (p < 0.05). The particle size of microparticles was in the range of 10-250 microm, and most microspheres had a particle size smaller than 100 microm. Only the volume of petroleum benzin showed a significant effect on the particle size of prepared microspheres (p < 0.05). Both the initial drug loading and the addition of nonsolvent significantly affected the initial release of fenoterol from the ethyl cellulose microspheres. The diffusion-controlled release followed by a constant release was exhibited in these microspheres.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Effect of formulation variables on in vitro drug release and micromeritic properties of modified release ibuprofen microspheres.

Modified release microspheres of the non-steroidal anti-inflammatory drug, ibuprofen, were formulated and prepared using the emulsion solvent diffusion technique. The contribution of various dispersed phase and continuous phase formulation factors on in vitro drug release and micromeritic characteristics of microspheres was examined. The results demonstrated that the use of Eudragit RS 100 and Eudragit RL 100 as embedding polymers modified the drug release properties as a function of polymer type and concentration. Eudragit RS 100 retarded ibuprofen release from the microspheres to a greater extent than Eudragit RL 100. The drug/polymer concentration of the dispersed phase influenced the particle size and drug release properties of the formed microspheres. It was found that the presence of emulsifier was essential for microsphere formation. Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release properties. Scanning electron microscopy revealed profound distortion in both the shape and surface morphology of the microspheres with the use of magnesium stearate as added emulsifier. The application of an additional Eudragit RS 100 coat onto formed microspheres using fluid bed technology was successful and modulated the drug release properties of the coated microspheres.

Delayed-Action Preparations↗
PubMed2005

Controlled drug delivery systems based on thiolated chitosan microspheres.

The aim of the present study was to verify the potential of chitosan-thio-butyl-amidine (TBA) microspheres as carrier systems for controlled drug delivery. In this study microspheres were prepared utilizing water in oil (w/o) emulsification solvent evaporation technique. A concentration of 0.5% of chitosan-TBA conjugate displaying 100 microM thiol groups per gram polymer was used in the aqueous phase of the emulsion in order to prepare microspheres. The obtained non-aggregated free-flowing microspheres were examined with conventional light microscope as well as scanning electron microscopy (SEM). The microscopic images indicated that the prepared chitosan-TBA microspheres were of spherical shape and smooth surface while microparticles obtained from the unmodified chitosan were of porous structure and non-spherical shape. Particle size distribution was determined to be in the range from 1 to 59 microm. The free thiol group content of chitosan-TBA microspheres prepared with an aqueous phase of pH 2, 5, and 6.5 were determined to be 71.4, 49.4, and 8.2 microM/g polymer, respectively. Furthermore, results attained from in vitro release studies with fluorescein isothiocyanate labelled dextran (FITC-dextran) loaded chitosan-TBA microspheres showed a controlled release rate for more than three hours while the control reached the maximum peak level of release already within an hour. According to these results, chitosan-TBA microspheres seem to be a promising tool in transmucosal drug delivery for poorly absorbed therapeutic agents.

Chitin↗