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PubMed2001

[Intravitreally injectable poly (D, L-Lactide) microspheres containing dexamethasone acetate for sustained release].

AIM: To prepare and evaluate dexamethasone acetate-loaded poly (d, l-lactide) microspheres for sustained release in vitro and their therapeutic effect on proliferative vitreoretinopathy in vivo. METHODS: The microspheres were prepared by a solvent evaporation/extraction technique. Properties such as geometric mean diameter, span, drug loading, rate of entrapment and release characteristics were evaluated. Differential scanning calorimetry and X-ray powder diffractometry were used to identify the physical phase of dexamethasone acetate in poly (d, l-lactide) matrix, and safety in vivo was examined. Effect of drug-loaded microspheres on suppression of experimental proliferative vitreoretinopathy was studied in albino rabbit eyes after an intravitreal injection of macrophages. RESULTS: The geometric mean diameter and span of the microspheres were 62.9 microns and 0.92, respectively. Drug loading and rate of entrapment of dexamethasone acetate in microspheres were 17.5% and 86.5%, respectively. Differential scanning calorimetry and X-ray powder diffractometry showed that dexamethasone acetate dispersed uniformly as molecules in poly (d, l-lactide) matrix. Ninety percent of the dexamethasone acetate was released in vitro from dexamethasone acetate after 48 days, while the same amount released from microspheres took 90 days. Storage under 4 degrees C in refrigerator or 25 degrees C in a dessicator at a relative humidity of 75% for 90 days had little effect on the properties of the microspheres. Intravitreal injection of microspheres showed a sustained release and continuous action of dexamethasone acetate for 84 days. After injection of activated macrophages, the groups of blank microspheres and dexamethasone acetate showed proliferation to different extent, while the base of the eye remained clear and no obvious proliferation was observed for the group of microspheres. A significant difference exists between these three groups. CONCLUSION: Poly (d, l-lactide) microspheres containing dexamethasone acetate is a potentially promising delivery system for the suppression of proliferative vitreoretinopathy.

Animals↗

PubMedDate not supplied

Co-encapsulation of two plasmids in chitosan microspheres as a non-viral gene delivery vehicle.

PURPOSE: The aims of this study are to encapsulate two different plasmid DNAs (pGL2 and pMK3) in the same microsphere structure and to investigate in vivo transfection characteristics of chitosan microspheres. Furthermore, the effect of formulation factors, such as chitosan concentration and plasmid DNA amount on in vitro properties of microspheres were studied. METHODS: Double plasmid-loaded chitosan microspheres were prepared by complex coacervation. Release studies were done in phosphate buffered saline at 37 degrees C and released plasmid DNA was determined spectrophotometrically. Integrity of plasmid DNAs was checked by agarose gel electrophoresis. For in vivo transfection studies, microspheres were injected into the muscle of the mice and expression of proteins (beta-galactosidase and luciferase) was measured. RESULTS: High encapsulation efficiency was obtained with chitosan microspheres (90%). The size of particles was about 1.15 - 1.28 m. No dependence was observed between the size and formulation variables (chitosan concentration and the amount of plasmid). After encapsulation process, integrity of two plasmids did not change. Plasmid DNAs were continuously released from chitosan microspheres. Chitosan concentrations and plasmid amounts affected in vitro release properties. After intramuscular injection of double plasmids loaded microspheres into muscle of the mice, co-expression was obtained. High beta-galactosidase and luciferase productions were determined with these microspheres after a long post-transfection period (12 weeks). CONCLUSIONS: Our results showed that two plasmids could be encapsulated in chitosan microspheres without affecting their structural and functional integrity. Thus, sustained and high protein production was obtained with these microspheres.

Animals↗

PubMedDate not supplied

Evaluation of biodegradable microspheres as vaccine adjuvant for hepatitis B surface antigen.

Biodegradable microspheres were evaluated as vaccine adjuvants based on their ability to provide prolonged release of incorporated agents. Hepatitis B surface antigen (HBSA) prepared by recombinant DNA technology was chosen as a model antigen and encapsulated into polyglycolic acid (PGA) by solvent extraction and solvent evaporation techniques. Five microsphere formulations were prepared to evaluate effect of microsphere size and the presence of immunostimulants such as muramyl dipeptide (MDP) or aluminum hydroxide. The microspheres were characterized for size distribution, surface morphology and antigenicity. Guinea pigs were chosen as the animal model for evaluation of antigenicity of the formulations. The animals were divided into seven groups of four animals each and the microsphere formulations were injected intraperitoneally, using alum adsorbed HBSA as positive control and placebo microspheres as negative control. Blood samples were withdrawn from the animals by toe clipping at two, four, six and sixteen weeks and plasma was analyzed for antibodies against hepatitis B by an enzyme linked immunoassay. At sixteen weeks, the animals were reinjected and evaluated for antibody response at two, four and six weeks post second injection. Antibody response to the microspheres was higher than control. Smaller size microspheres elicited earlier antibody response while the larger size microspheres provided delayed and longer duration of antibody production. Microspheres with MDP potentiated the antibody response. The results demonstrate the applicability of biodegradable microspheres for immunization against hepatitis B.

Adjuvants, Immunologic↗

PubMed2005

[The preparation and the in vitro release of OANO-1 microspheres].

OBJECTIVE: To prepare OANO-1 microspheres and test their release in vitro. METHOD: OANO-1 microspheres were made by W/O/W-liquid drying process. The surface morphology of the microspheres was observed by SEM. The mean diameter and the size distribution of microspheres, the drug loading and the incorporation efficiency were examined. The release of OANO-1 microspheres in vitro was examined by small cup method. The accumulated release percent of OANO-1 microspheres was examined. RESULT: The OANO-1 microspheres were regular in their morphology. The average particle size was 8.59 microm with over 90% of the microspheres being in the range of 1-12 microm. The drug loading and the incorporation efficiency were 48.39% and 19.32% respectively. The accumulated release percent of OANO-1 microspheres was 78.4% after 108 h. The release half-life t1/2 was 40.8 h and Higuchi equation was Y = 0.1326 X - 0.4782, r = 0.9951. CONCLUSION: The preparation of OANO-1 microspheres was well. The release in vitro of OANO-1 microspheres showed significant sustained release.

Angelica sinensis↗

PubMed2006

[Immunogenicity of single-dose HBsAg-PLGA controlled release microspheres in mice].

AIM: To investigate the level of immune response and the immune mechanism of the single-dose hepatitis B surface antigen (HBsAg)-poly (d, l)-lactide-co-glicolide acid (PLGA) microspheres in BALB/c mice. METHODS: Three kind of HBsAg-PLGA microspheres, HBsAg-PLGA50/50-COOH microspheres, HBsAg-PLGA75/25 microspheres and HBsAg-PLGA50/50 microspheres, were prepared by double emulsion microencapsulation technique used three kinds of PLGA with different L/G ratio. The single-dose of HBsAg-PLGA microspheres was subcutaneously injected into BALB/c mice at the dose of 7.5 microg HBsAg per mouse. The conventional aluminum-adjuvant vaccine was subcutaneously injected at 0, 1 and 2 month as positive control. In certain time interval, the induced immune level of total antibody was detected by enzyme linked immunosorbent assay (ELISA). For subclass of IgG antibody and cytokines studies, the dose of HBsAg was 2.5 microg per mouse. RESULTS: The HBsAg-PLGA microspheres could successfully induce a humoral immune response in BALB/c mice. Compared with the conventional aluminum-adjuvant vaccine, the antibody response of the HBsAg-PLGA50/50-COOH microspheres was significantly lower than the group received three injections of aluminum-adjuvant vaccine (P < 0.01) except for a higher priming response during the early 6 weeks. The results were ascribed to the relatively rapid degradation charactics of PLGA50/50-COOH polymer. The immune response for the HBsAg-PLGA50/50 microspheres and HBsAg-PLGA75/25 microspheres were comparable to the group administered with aluminum-adjuvant vaccine (P > 0.05) which was due to the sustained degradation of PLGA50/50 and PLGA75/25 polymer. CONCLUSION: The HBsAg-PLGA microsphere is a promising candidate for the controlled delivery of a vaccine which does not require multiple injections.

Animals↗

PubMed1991

Microspheres of biodegradable polymers as a drug-delivery system in the vitreous.

Microspheres of biodegradable polymers were evaluated as a potential controlled-release drug-delivery system in the vitreous. The microspheres were prepared with polymers of poly(lactic acid) or copolymers of glycolic acid and lactic acid. The release of 5-fluorouracil (5-FU) from the microspheres was studied in vitro. Poly(lactic acid) microspheres released 70-85% of total 5-FU over 7 days. Microspheres of polymers with a smaller molecular weight released the drug more rapidly. Copolymer microspheres released 98% of 5-FU over 2 days. The rate of drug release was controllable by changing the molecular weight of the polymers or using a matrix of copolymer. The intravitreal kinetics of the microspheres were studied in ten rabbits in vivo. A suspension of microspheres was injected into the vitreous cavity of five normal eyes and five vitrectomized eyes. By 48 +/- 5.2 days after injection, the microspheres disappeared from the vitreous cavity in the five normal eyes. Clearance from the vitreous cavity was accelerated in the five rabbits that underwent vitrectomy (14 +/- 2.4 days; P less than 0.001). No difference was found in the b waves of electroretinograms before and after injection of the microspheres. The histologic study showed no abnormal findings as a result of the injection. These results suggested that microspheres of biodegradable polymers may be a potential delivery system for the controlled release of drugs in the vitreous.

Animals↗

PubMed1990

Evaluation of blood flow measurements with microspheres and rubidium--an experimental study in rats.

The microsphere method has been widely used for blood flow measurements in normal and tumour tissues. The microsphere method was evaluated for repeated measurements of cardiac output and regional blood flow in anesthetised rats and in anesthetised rats given noradrenalin and thereby having altered haemodynamics with special emphasis on liver blood flow. Comparing the microsphere method with the soluble indicator method (86Rubidium) gave equal cardiac output values. The liver blood flow was lower and the spleen blood flow was higher with the microsphere method. Two microsphere injections at 10 min intervals were performed on anesthetised rats. In one group 817 +/- 10(3) microspheres were injected each time, in a second group 436 +/- 10(3) and in a third noradrenalin was added and then 430 +/- 10(3) microspheres injected twice. There was good reproducibility for cardiac output and for most organ and tissue blood flows between first and second microsphere injection. No influence on arterial liver blood flow was seen. A blood pressure fall and a decreased heart rate was registered after the first injection in the group given 817 x 10(3) spheres. There was also a blood pressure fall in the group given noradrenalin after the first microsphere injection. The microsphere method with two injections of 436 x 10(3) microspheres seems adequate to use in arterial blood flow studies of the liver and simultaneous cardiac output measurements.

Animals↗

PubMedDate not supplied

Validation of cardiac single photon emission tomography of labeled intracoronary microspheres as a method to measure changes in distribution of coronary blood flow.

Single photon emission tomography (SPECT) combined with intracoronary dual-labelled microspheres (Tc-99m and In-111) is a technique that can potentially measure changes in regional coronary blood distribution. To validate the ability of microspheres to measure regional coronary flow distribution, we studied this method in 5 pigs to evaluate 3 specific questions: Does the lack of attenuation correction affect the calculation of relative concentrations of microspheres? Do Tc and In microspheres have similar imaging characteristics? Is there correlation between tomographic concentrations of tracer activity and tissue concentration of microspheres? Tc and In albumin microspheres were injected selectively down the left anterior descending coronary artery, and dual-isotope SPECT imaging of the whole heart was carried out. The heart was then sliced and the slices imaged directly on the collimator. Finally the slice was sectioned and well counted. The correlation coefficient (R) between SPECT profiles and direct camera profiles was 0.91. The R between In and Tc counts was also excellent at 0.93. Comparing SPECT profiles and well counting, the R was 0.79 for Tc and 0.72 for In microspheres, with the standard error of estimate less than 8.7% and 14.5% respectively about the mean value. Therefore; SPECT of intracoronary microspheres does correspond to tissue concentrations of microspheres, lack of attenuation correction does affect the correlation but not to a significant extent, In and Tc microspheres have very similar imaging characteristics. SPECT of dual intracoronary microspheres may provide a potentially useful tool to assess distribution of regional coronary blood flow.

Animals↗

PubMed1993

Biochemical characterization of air-filled albumin microspheres.

Heating and sonication of a solution of human serum albumin (HSA) yields air-filled microspheres that can be used as a contrast agent in ultrasound examinations. The microspheres are stabilized by a thin-layer of protein surrounding the air bubbles. As long as the microspheres were intact, the protein was insoluble in aqueous solutions. After disintegration of the microspheres, the protein could be solubilized in several solutions. The intermolecular interactions in the microsphere protein have been elucidated from its solubility properties. The microspheres were disintegrated by several detergents which also solubilized the protein. After pressure disintegration of the microspheres, the protein was solubilized immediately in urea and guanidinium chloride, and also in phosphate-buffered saline after incubation overnight. These results indicate that the protein was mainly stabilized by non-covalent forces. The solubilization in buffer was inhibited by a high salt concentration, suggesting that hydrophobic interactions were involved in stabilizing the microsphere structure. Analysis of the solubilized protein by gel filtration showed that the protein contained substantial amounts of soluble aggregates of HSA. Reduction of the disulphide bonds dissolved these aggregates into monomeric HSA, showing that intermolecular disulphide bonds were also involved in stabilization of the microspheres. The solubilized protein also contained less fatty acids than the soluble HSA used for the production of microspheres. These results show that the microsphere protein has the same characteristics as heat-denatured HSA.

Air↗

PubMed1995

[A study on accuracy of rCBF measurements using the conventional microsphere method with N-isopropyl-p-[123I]iodoamphetamine and SPECT].

To evaluate the accuracy of conventional microsphere method for the measurement of regional cerebral blood flow (rCBF) based on the microsphere model with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) and SPECT, we performed simulation analysis and clinical studies. Although the microsphere method requires early SPECT scan at a few minutes after injection of the tracer for the accurate measurement of rCBF, the conventional microsphere method, which is generally used, requires more delayed SPECT scan with long scan-duration. In the conventional microsphere method, the delayed SPECT image is corrected to the image at a few minutes after injection of the tracer by using the monitored entire brain activity. By the simulation analysis based on the 2-compartment model (influx; K1 and outflux; k2) using the input function and the entire brain activity obtained from eight subjects respectively, it was found that the conventional microsphere method overestimated the rCBF in the practical range of rCBF and Vd (= K1/k2) given in the 2-compartment model. When the values of rCBF and Vd in the 2-compartment model were given at 0.5 (ml/g/min) and 30 (ml/g) respectively, the rate of overestimation of rCBF by the conventional microsphere method was determined to be 17.3 +/- 0.7% (mean +/- S.D.). Also in clinical studies for eight subjects, the conventional microsphere method overestimated the rCBF compared with those evaluated by non-linear least squares fitting (NLLSF) analysis based on the 2-compartment model. Those results agreed well with the simulation analysis, suggesting the validity of the simulation. The rCBF values clinically estimated by the conventional method were, however, significantly correlated with those calculated by NLLSF analysis, and there were not so much difference between the two quantitative rCBF images obtained by the conventional microsphere method and the microsphere method. Therefore, we conclude that the conventional microsphere method is clinically useful in spite of the overestimation of rCBF.

Amphetamines↗

PubMed1997

Ganciclovir-loaded polymer microspheres in rabbit eyes inoculated with human cytomegalovirus.

PURPOSE: To test the antiviral effect of ganciclovir released from biodegradable polymer microspheres in rabbit eyes inoculated with human cytomegalovirus (HCMV). METHODS: Human cytomegalovirus (5 x 10(3) plaque forming unit in 0.1 ml Hank's balanced salt solution) was inoculated 4 days after gas compression vitrectomy. Injected after 2 days was 10 mg of 300- to 500-micron ganciclovir-loaded microspheres (89.77 micrograms ganciclovir/mg) suspended in 0.1 ml of 2% hydroxypropylmethylcellulose. Blank microspheres were injected as control specimens. Vitritis, retinitis, and optic neuritis were graded from 0(+)-4+ for 14 days to separate the early HCMV-induced disease events from later nonspecific host inflammatory responses. Ganciclovir-loaded microspheres also were injected and observed for biodegradation and tissue reaction for 8 weeks. RESULTS: In eyes injected with ganciclovir-loaded microspheres, vitritis decreased from days 3 to 14, and retinitis and optic neuritis decreased from days 3 to 9. In eyes injected with blank microspheres, vitritis increased from days 3 to 7, retinitis increased from days 3 to 9, and optic neuritis increased from days 3 to 14. Immunofluorescence of HCMV antigens in retinal tissues was shown only in eyes injected with blank microspheres. Histopathologic analysis showed minimal focal disruption of the retinal architecture in eyes injected with ganciclovir-loaded microspheres. Disorganization of the normal retinal architecture was observed in eyes injected with blank microspheres. No adverse tissue reaction was observed clinically and histopathologically in eyes injected with ganciclovir-loaded microspheres after 8 weeks. CONCLUSIONS: Ten milligrams of 300 to 500 microns ganciclovir-loaded poly(D,L-lactide-co-glycolide) microspheres control the progression of fundus disease in HCMV-inoculated rabbit eyes.

Animals↗

PubMed1998

Size Dependence of Polymer Composition in the Surface Layer of Poly(acrylamide-co-acrylic acid) Hydrogel Microspheres

Poly(acrylamide-co-acrylic acid) hydrogel microspheres of four different average sizes were prepared using a membrane emulsification technique. These four kinds of microspheres had average diameters of 1.35, 2.33, 3.09, and 7.43 &mgr;m in distilled water and were all fairly monodisperse. Their surface properties were studied by measuring the electrophoretic mobility of the microspheres. The mobility values were negative at pH 7.4 with the ionic strengths between 0.005 and 0.154 at 25°C. More negative mobility values were obtained with smaller microspheres than the larger ones. By analyzing the data with an electrokinetic theory for "soft" surfaces, it was found that smaller microspheres have higher surface charge density than the larger ones, although all kinds of microspheres were prepared from monomer solutions with the same monomer composition. The observed size dependence of the electrophoretic mobility suggests that copolymerization of acrylamide monomers and acrylic acid monomers does not proceed homogeneously within a microsphere. That is, charged acrylic acid monomers have a tendency to be localized in the microsphere core region, whereby the surface region of microspheres becomes poor in charges, reducing the mobility of larger microspheres. This is not the case for smaller microspheres, so that their mobility becomes more negative. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

PubMed2006

The effect of different grades of PLGA on characteristics of microspheres encapsulated with cyclosporine A.

The aim of this study was to evaluate the effect of different grades of poly D, L lactide-co-glycolide (PLGA) on the properties of microspheres encapsulated with Cyclosporine A (CyA). Microspheres were prepared by solvent evaporation method using three grades of PLGA. Various characteristics of microspheres such as morphology, size distribution, encapsulation efficiency and release profile were evaluated. Complementary studies were also carried out by Infrared (IR) spectroscopy and Differential scanning calorimetry (DSC) to evaluate possible drug-polymer interactions. Scanning electron microscopy (SEM) studies showed microspheres as spherical particles with CyA deposited as islands on the surface of spheres. Particle size range was 1-25 microm for microspheres made of PLGA (50:50) which showed the minimum size. Encapsulation efficiency was found to vary from 75% to 92% in various formulations. The profile of release was biphasic, showing an initial rapid phase followed by a continuous and slower rate thereafter. Microspheres made of grades 50:50 and 85:15 showed the highest and lowest amount of drug release, respectively. IR spectra for drug, polymer and microspheres did not indicate any chemical interaction between the components of microsphere and DSC thermograms revealed that CyA was present in its amorphous state within microspheres. In conclusion, the effect of polymer characteristics should be considered in microsphere formulations. In this study, suitable microspheres especially with PLGA (50:50) were prepared which allow the controlled release of CyA over a prolonged period of time.

Calorimetry, Differential Scanning↗

PubMed1988

Macrophage phagocytosis of biodegradable microspheres composed of L-lactic acid/glycolic acid homo- and copolymers.

A variety of biodegradable microspheres were prepared from L-lactic acid, DL-lactic acid, or glycolic acid homopolymers and copolymers of different molecular weights and monomer compositions. Phagocytosis of the microspheres by mouse peritoneal macrophages was studied in cell culture system using scanning electron microscopy as well as light microscopy. The diameter of microspheres prepared was less than 2 microns, regardless of the starting polymers. No dependence of the chemical nature of starting polymers was observed on the extent of phagocytosis of the microspheres by macrophages. Precoating the microspheres with water-soluble macromolecules such as proteins had great influence on phagocytosis by macrophages. It was demonstrated that precoating with bovine serum albumin and non-proteinaceous macromolecules reduced the phagocytosis of microspheres, while bovine gamma-globulin, human fibronectin, bovine tuftsin, and gelatin precoating enhanced the phagocytosis. This trend was not influenced by the presence of serum. Only in the case of gelatin precoating, the phagocytosis was greatly enhanced by the presence of serum as compared to precoating with other proteins. Microscopic observation clearly indicated that the phagocytosed microspheres were gradually degraded in the macrophage interior with the incubation time, leading to release of a fluorescent dye encapsulated in the microspheres. The rate of microsphere degradation in cells could be controlled by changing the molecular weight and the monomer composition of the copolymers comprising the microspheres.

Animals↗

PubMed2004

PLA and PLGA microspheres of beta-galactosidase: Effect of formulation factors on protein antigenicity and immunogenicity.

The entrapment of beta-galactosidase (Escherichia coli) in PLA and PLGA microspheres using a double emulsion technique resulted to significant reduction of protein antigenicity. The extent of antigenicity loss depended on the conditions of microsphere preparation. Most of antigenicity loss occurred on the first emulsification step. Only the effects of microsphere preparation factors having an important influence on protein antigenicity, such as the type of organic phase (polymer solvent) and homogenization, could be predicted (on a qualitative basis) by antigenicity data obtained after the first emulsification step. The type of polymer and polymer solvent used to prepare the microspheres affected beta-galactosidase immunogenicity. The PLA microspheres prepared using ethyl acetate was the most immunogenic microsphere formulation, eliciting similar total antibody responses as the alum formulation of beta-gal. This formulation was the only microsphere formulation that induced an IgG1/IgG2a ratio lower than 1, indicating an immune response biased towards a Th1 type. The results obtained indicate that large protein molecules with complex tertiary structure such as beta-galactosidase can be entrapped in PLA and PLGA microspheres with retention of protein immunogenic potential, providing that appropriate conditions of microsphere preparation are applied, and that the formulation of microspheres might influence the Th1/Th2 type of immune response against the encapsulated antigen.

Animals↗

PubMed2007

Preparation and preliminary characterization of concentric multi-walled chitosan microspheres.

Chitosan was first converted into micro-droplets by using a high voltage electrostatic field system. The droplets were then dropped into a series of Na(5)P(3)O(10)/NaOH solution mixtures with volume ratio of 17:3, 19:1, 1:0 (pure aqueous Na(5)P(3)O(10)) or 0:1 (pure aqueous NaOH) in order to fabricate chitosan microspheres with different membrane structures. The microspheres exhibit distinct chemical and physical properties, including release behaviors of encapsulated drugs. These chitosan microspheres prepared by this method exhibited good sphericity within the range of (286.6 +/- 15.9) to (356 +/- 9.5) microm in diameters. SEM observations have indicated that the chitosan microspheres exhibited distinct surface structures depending on the post-treatment solutions. The mechanical strength of the chitosan microspheres significantly improved upon treatment with Na(5)P(3)O(10)/NaOH solution at ratio of 17:3 (v/v), as compared with the same but at ratio of 19:1, 1:0 (pure Na(5)P(3)O(10)) and 0:1 (pure NaOH) solutions. In addition, chitosan microspheres with unique multi-walled concentric shell membrane structures were prepared by treating with Na(5)P(3)O(10)/NaOH solution at ratio of 19:1. Release studies were carried out to evaluate the kinetic profiles of two model drugs (5-fluorouracil and cytochrome C) from these prepared chitosan microspheres. When chitosan microspheres treated with Na(5)P(3)O(10)/NaOH ratio at 17:3, the release of cytochrome C was found to be the slowest as compared to those treated by the same Na(5)P(3)O(10)/NaOH solution of other mixing ratios, after a period of 35-day "endurance" test. However, in one case, 5-fluorouracil released quite quickly in a period of 30 min (about 80% completion). The wide range of drug release results might be attributed to the unique and wide range of surface characteristics, porosities, and various structures of chitosan microspheres upon treatment with Na(5)P(3)O(10)/NaOH solutions. These results indicate that, by adjusting the Na(5)P(3)O(10)/NaOH ratios, without extra manipulation on polymer material formulation, one could obtain an additional degree of freedom in drug release profile that permits the simultaneous regulation of morphologies of surface texture and internal structure, mechanical properties, and molecular permeability of the microspheres.

Albumins↗

PubMed2006

Biodegradable and complexed microspheres used for sustained delivery and activity protection of SOD.

To develop a new protein delivery system for superoxide dismutase (SOD), biodegradable materials like poly(DL-lactide-co-glycolide) (PLGA), alginate, and chitosan were used for preparing PLGA microspheres and alginate-chitosan microspheres, which were used for encapsulating protein. Alginate-chitosan microspheres showed much higher entrapment efficiency (91.08% +/- 1.28%) than that of PLGA microspheres (36.42% +/- 1.81%). In vitro release study showed that SOD presented a sustained release character in the preparation of these biodegradable materials. After 15 days, 43.72% +/- 0.43% of protein was released from alginate-chitosan microspheres, while there was 62.96% +/- 3.95% of protein release from PLGA microspheres. However, alginate-chitosan demonstrated that it was a better material to control the burst release of protein from microspheres. Furthermore, SOD activity in microspheres was evaluated, and the results showed that microspheres protected the activity of protein to some extent. Finally, PLGA-alginate-chitosan complex microspheres were constructed and the release character in vitro demonstrated that this preparation could not only prolong the release of drug but also decrease the burst release.

Alginates↗

PubMed1993

Aerosolized fluorescent microspheres detected in the lung using confocal scanning laser microscopy.

Aerosolized fluorescent microspheres were used to study particle deposition in site-specific regions of the lung with confocal laser scanning microscopy. A nebulizer was used to aerosolize microspheres followed by passage through a heated discharging column to reduce static charge and to remove water surrounding each microsphere. Precoating of microspheres with albumin helped to minimize displacement during vascular fixation of the lungs. Confocal laser microscopy facilitated visualization of microspheres throughout the bronchial tree, ducts, and alveoli of the lungs. The use of fluorescent microspheres and confocal laser imaging provided distinct advantages compared with other methods to study lung particle deposition due to (1) the generation of single microspheres of uniform size by nebulization, (2) easy detection of microspheres in large slabs of microdissected lung tissues, (3) excellent resolution of tissue surfaces and microspheres for an infinite number of orientations and planes of section, and (4) the ability to visualize microspheres below fluid lining layers and on surfaces that could not easily be done by other methods of microscopy.

Aerosols↗