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Sample records for acid microsphere radioembolisation

  1. Protocell-like Microspheres from Thermal Polyaspartic Acid

    NASA Astrophysics Data System (ADS)

    Bahn, Peter R.; Pappelis, Aristotel; Bozzola, John

    2006-12-01

    One of the most prominent amino acids to appear in monomer-generating origin-of-life experiments is aspartic acid. Hugo Schiff found in 1897 that aspartic acid polymerizes when heated to form polyaspartylimide which hydrolyzes in basic aqueous solution to form thermal polyaspartic acid which is a branched polypeptide. We recently reported at the ISSOL 2005 Conference that commercially made thermal polyaspartic acid forms microspheres when heated in boiling water and allowed to cool. In a new experiment we heated aspartic acid at 180°C for up to 100 h to form thermal polyaspartylimide which when heated in boiling water without addition of base hydrolyzed to form thermal polyaspartic acid which upon cooling formed microspheres. Thermal polyaspartic acid microspheres appear protocell-like in the sense of being prebiotically plausible lattices or containers that could eventually have been filled with just the right additions of primordial proteins, nucleic acids, lipids, and metabolites so as to constitute protocells capable of undergoing further chemical and biological evolution. Thermal polyaspartic acid microspheres are extremely simple models of protocells that are more amenable to precise quantitative experimental investigation than the proteinoid microspheres of Sidney W. Fox. We present here scanning electron microscope images of such thermal polyaspartic acid microspheres. Figure 1 shows thermal polyaspartic acid microspheres from l-aspartic acid heated at 180°C for 50 h, at a magnification of 3,500×. Figure 2 shows thermal polyaspartic acid microspheres from the same sample at a magnification of 7,000×. The thermal polyaspartic acid microspheres have a diameter of approximately 1 μm These images were viewed with a Hitachi S2460N scanning electron microscope at 20 kV acceleration voltage. [Figure not available: see fulltext.][Figure not available: see fulltext.

  2. Textiles with gallic acid microspheres: in vitro release characteristics.

    PubMed

    Martí, Meritxell; Martínez, Vanessa; Carreras, Núria; Alonso, Cristina; Lis, Manuel José; Parra, José Luis; Coderch, Luisa

    2014-01-01

    Abstract The aim of this study was to demonstrate the skin penetration of an antioxidant, gallic acid (GA), encapsulated in poly-ε-caprolactone (PCL) microspheres and applied onto textile fabrics, by a specific in vitro percutaneous absorption methodology. Two techniques (particle size distribution and FTIR) were used to characterise the microspheres obtained. The amount of GA-loaded microspheres present in the biofunctional textiles was established before their use as a textile drug delivery system. More absorption and desorption of microspheres with GA for the polyamide fabric were found in comparison with cotton fabric. The percutaneous absorption results indicated that the skin penetration of GA released from PCL-microspheres that were applied directly to the skin was higher than when GA was embedded within biofunctional textiles, in conclusion, an interesting reservoir effect may be promoted when biofunctional textiles were used.

  3. [Study on preparation process of artesunate polylactic acid microspheres].

    PubMed

    Pan, Xu-Wang; Wang, Wei; Fang, Hong-Ying; Wang, Fu-Gen; Cai, Zhao-Bin

    2013-12-01

    This study aims to investigate the preparation process and in vitro release behavior of artesunate polylactic acid microspheres, in order to prepare an artesunate polylactic acid (PLA) administration method suitable for hepatic arterial embolization. With PLA as the material and polyvinyl alcohol (PVA) as the emulsifier, O/W emulsion/solvent evaporation method was adopted to prepare artesunate polylactic acid microspheres, and optimize the preparation process. With drug loading capacity, encapsulation efficiency and particle size as indexes, a single factor analysis was made on PLA concentration, PVA concentration, drug loading ratio and stirring velocity. Through an orthogonal experiment, the optimal processing conditions were determined as follows: PLA concentration was 9. 0% , PVA concentration was 0. 9% , drug loading ratio was 1:2 and stirring velocity was 1 000 r x min(-1). According to the verification of the optimal process, microsphere size, drug loading and entrapment rate of artesunate polylactic acid microspheres were (101.7 +/- 0.37) microm, (30.8 +/- 0.84)%, (53.6 +/- 0.62)%, respectively. The results showed that the optimal process was so reasonable and stable that it could lay foundation for further studies.

  4. Microspheres

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Vital information on a person's physical condition can be obtained by identifying and counting the population of T-cells and B-cells, lymphocytes of the same shape and size that help the immune system protect the body from the invasion of disease. The late Dr. Alan Rembaum developed a method for identifying the cells. The method involved tagging the T-cells and B-cells with microspheres of different fluorescent color. Microspheres, which have fluorescent dye embedded in them, are chemically treated so that they can link with antibodies. With the help of a complex antibody/antigen reaction, the microspheres bind themselves to specific 'targets,' in this case the T-cells or B-cells. Each group of cells can then be analyzed by a photoelectronic instrument at different wavelengths emitted by the fluorescent dyes. Same concept was applied to the separation of cancer cells from normal cells. Microspheres were also used to conduct many other research projects. Under a patent license Magsphere, Inc. is producing a wide spectrum of microspheres on a large scale and selling them worldwide for various applications.

  5. Production and characterization of 166Ho polylactic acid microspheres.

    PubMed

    Yavari, Kamal; Yeganeh, Ehsan; Abolghasemi, Hossein

    2016-01-01

    Microsphere and particle technology with selective transport of radiation represents a new generation of therapeutics. Poly-L-lactic acid (PLLA) microspheres loaded with holmium-166 acetylacetonate ((166)Ho-PLLA-MS) are novel microdevices. In this research, (165)HoAcAc-PLLA microparticles were prepared by the solvent evaporation technique. Microspheres were irradiated at Tehran Research Reactor. The diameter and surface morphologies were characterized by particle sizer and scanning electron microscopy before and after irradiation. The complex stability, radiochemical purity, and in vivo biodistribiotion were checked in the final solution up to 3 days. In this study, (166)Ho-PLLA spherical particles with a smooth surface and diameter of 20-40 µm were obtained, which were stable in vitro and in vivo studies. Neutron irradiation did not damage the particles. The ease with which the PLLA spheres could be made in the optimal size range for later irradiation and their ability to retain the (166)Ho provided good evidence for their potential use in radioembolization.

  6. In vitro and in vivo evaluation of mucoadhesive microspheres prepared for the gastrointestinal tract using polyglycerol esters of fatty acids and a poly(acrylic acid) derivative.

    PubMed

    Akiyama, Y; Nagahara, N; Kashihara, T; Hirai, S; Toguchi, H

    1995-03-01

    Two types of polyglycerol ester of fatty acid (PGEF)-based microspheres were prepared: Carbopol 934P (CP)-coated microspheres (CPC-microspheres) and CP-dispersion microspheres (CPD-microspheres). Comparative studies on mucoadhesion were done with these microspheres and PGEF-based microspheres without CP (PGEF-microspheres). In an in vitro adhesion test, the CPD-microspheres adhered strongly to mucosa prepared from rat stomach and small intestine because each CP particle in the CPD-microsphere was hydrated and swelled with part of it remaining within the microsphere and part extending to the surface serving to anchor the microsphere to the mucus layer. The gastrointestinal transit patterns after administration of the CPD-microspheres and PGEF-microspheres to fasted rats were fitted to a model in which the microspheres are emptied from the stomach monoexponentially with a lag time and then transit through the small intestine at zero-order. Parameters obtained by curve fitting confirmed that the gastrointestinal transit time of the CPD-microspheres was prolonged compared with that of the PGEF-microspheres. MRT in the gastrointestinal tract was also prolonged after administration of the CPD-microspheres compared with that following the administration of the PGEF-microspheres.

  7. Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

    NASA Astrophysics Data System (ADS)

    Li, Fengxia; Li, Xiaoli; Li, Bin

    2011-11-01

    In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.

  8. Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation.

    PubMed

    Wu, Junzi; Williams, Gareth R; Branford-White, Christopher; Li, Heyu; Li, Yan; Zhu, Li-Min

    2016-09-20

    In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.

  9. Cationic poly(lactic-co-glycolic acid) iron oxide microspheres for nucleic acid detection

    NASA Astrophysics Data System (ADS)

    Pandey, Chandra Mouli; Sharma, Aditya; Sumana, Gajjala; Tiwari, Ida; Malhotra, Bansi Dhar

    2013-04-01

    Herein, we envisage the possibility of preparing stable cationic poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating the iron oxide nanoparticles (IONPs; 8-12 nm). The IONPs are incorporated into PLGA in organic phase followed by microsphere formation and chitosan coating in aqueous medium via nano-emulsion technique. The average size of the microspheres, as determined by dynamic light scattering are about 310 nm, while the zeta potential for the composite remains near 35 mV at pH 4.0. These microspheres are electrophoretically deposited onto indium tin oxide (ITO)-coated glass substrate used as cathode and parallel platinum plate as the counter electrode. This platform is utilized to fabricate a DNA biosensor, by immobilizing a probe sequence specific to Escherichia coli. The bioelectrode shows a surface-controlled electrode reaction with the electron transfer coefficient (α) of 0.64 and charge transfer rate constant (ks) of 61.73 s-1. Under the optimal conditions, this biosensor shows a detection limit of 8.7 × 10-14 M and is found to retain about 81% of the initial activity after 9 cycles of use.Herein, we envisage the possibility of preparing stable cationic poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating the iron oxide nanoparticles (IONPs; 8-12 nm). The IONPs are incorporated into PLGA in organic phase followed by microsphere formation and chitosan coating in aqueous medium via nano-emulsion technique. The average size of the microspheres, as determined by dynamic light scattering are about 310 nm, while the zeta potential for the composite remains near 35 mV at pH 4.0. These microspheres are electrophoretically deposited onto indium tin oxide (ITO)-coated glass substrate used as cathode and parallel platinum plate as the counter electrode. This platform is utilized to fabricate a DNA biosensor, by immobilizing a probe sequence specific to Escherichia coli. The bioelectrode shows a surface-controlled electrode reaction with the

  10. Preparation and investigation the release behaviour of wax microspheres loaded with salicylic acid.

    PubMed

    Gifani, Aida; Taghizadeh, Mojtaba; Seifkordi, Ali A; Ardjmand, Mehdi

    2009-09-01

    Salicylic acid-beeswax microspheres were prepared by melt dispersion technique. The effects of formulation parameters on the microscopic characteristic, drug loading and cumulative amount of released drug were investigated by experimental design. Results showed that all of the microparticles were spherical with porous surfaces. The average size of microspheres was 24-48 microm, the drug content was in the range of 22-45% and the encapsulation efficiency was 46-93%. Drug loading was influenced by emulsification speed as a main factor. All the microspheres had a burst release initially. The emulsifier concentration did not have a significant effect on drug release. The release behaviour of microspheres conformed best to Korsmeyer-Peppas semi-empirical model and the release of SA from beeswax microspheres was Fickian (n < 0.45).

  11. The pharmacokinetics and pharmacodynamics of lidocaine- loaded biodegradable poly(lactic-co-glycolic acid) microspheres.

    PubMed

    Liu, Jianming; Lv, Xin

    2014-01-01

    The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(D,L-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34±0.3 μm. The poly disperse index was 0.21±0.03, and the zeta potential was +0.34±0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5%±4.3% and 11.2%±1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02-2.06-fold that of lidocaine injection (p<0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency.

  12. Poly(L-glutamic acid)/chitosan polyelectrolyte complex porous microspheres as cell microcarriers for cartilage regeneration.

    PubMed

    Fang, Jianjun; Zhang, Yun; Yan, Shifeng; Liu, Zhiwen; He, Shiming; Cui, Lei; Yin, Jingbo

    2014-01-01

    In this study a novel kind of porous poly(l-glutamic acid) (PLGA)/chitosan polyelectrolyte complex (PEC) microsphere was developed through electrostatic interaction between PLGA and chitosan. By adjusting the formula parameters chitosan microspheres with an average pore size of 47.5 ± 5.4 μm were first developed at a concentration of 2 wt.% and freeze temperature of -20 °C. For self-assembly of the PEC microspheres porous chitosan microspheres were then incubated in PLGA solution at 37 °C. Due to electrostatic interaction a large amount of PLGA (110.3 μg mg(-1)) was homogeneously absorbed within the chitosan microspheres. The developed PEC microspheres retained their original size, pore diameters and interconnected porous structure. Fourier transform infrared spectroscopy, thermal gravimetric analysis and zeta potential analysis revealed that the PEC microspheres were successfully prepared through electrostatic interaction. Compared with microspheres fabricated from chitosan, the porous PEC microspheres were shown to efficiently promote chondrocyte attachment and proliferation. After injection subcutaneously for 8 weeks PEC microspheres loaded with chondrocytes were found to produce significant more cartilaginous matrix than chitosan microspheres. These results indicate that these novel fabricated porous PLGA/chitosan PEC microspheres could be used as injectable cell carriers for cartilage tissue engineering. PMID:24025620

  13. Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery.

    PubMed

    Chen, Xingtao; Lv, Guoyu; Zhang, Jue; Tang, Songchao; Yan, Yonggang; Wu, Zhaoying; Su, Jiacan; Wei, Jie

    2014-01-01

    A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 μm to 79.7 μm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery.

  14. Safety evaluation of poly(lactic-co-glycolic acid)/poly(lactic-acid) microspheres through intravitreal injection in rabbits.

    PubMed

    Rong, Xianfang; Yuan, Weien; Lu, Yi; Mo, Xiaofen

    2014-01-01

    Poly(lactic-co-glycolic acid) (PLGA) and/or poly(lactic-acid) (PLA) microspheres are important drug delivery systems. This study investigated eye biocompatibility and safety of PLGA/PLA microspheres through intravitreal injection in rabbits. Normal New Zealand rabbits were randomly selected and received intravitreal administration of different doses (low, medium, or high) of PLGA/PLA microspheres and erythropoietin-loaded PLGA/PLA microspheres. The animals were clinically examined and sacrificed at 1, 2, 4, 8, and 12 weeks postadministration, and retinal tissues were prepared for analysis. Retinal reactions to the microspheres were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end staining and glial fibrillary acidic protein immunohistochemistry. Retinal structure changes were assessed by hematoxylin and eosin staining and transmission electron microscopy. Finally, retinal function influences were explored by the electroretinography test. Terminal deoxynucleotidyl transferase-mediated dUTP nick end staining revealed no apoptotic cells in the injected retinas; immunohistochemistry did not detect any increased glial fibrillary acidic protein expression. Hematoxylin and eosin staining and transmission electron microscopy revealed no micro- or ultrastructure changes in the retinas at different time points postintravitreal injection. The electroretinography test showed no significant influence of scotopic or photopic amplitudes. The results demonstrated that PLGA/PLA microspheres did not cause retinal histological changes or functional damage and were biocompatible and safe enough for intravitreal injection in rabbits for controlled drug delivery.

  15. Embolisation of the Gastroduodenal Artery is Not Necessary in the Presence of Reversed Flow Before Yttrium-90 Radioembolisation

    SciTech Connect

    Daghir, Ahmed A.; Gungor, Hatice; Haydar, Ali A.; Wasan, Harpreet S.; Tait, Nicholas P.

    2012-08-15

    Introduction: The gastroduodenal artery (GDA) is usually embolised to avoid nontarget dispersal before yttrium-90 (Y{sup 90}) radioembolisation to treat liver metastases. In a minority of patients, there is retrograde flow in the GDA. The purpose of this study was to determine if there is any increased risk from maintaining a patent GDA in patients with reversed flow. Materials and Methods: A retrospective review was performed of all patients undergoing Y{sup 90} radioembolisation at our institution. The incidence of toxicities arising from nontarget radioembolisation by way of the GDA (gastric/duodenal ulceration, gastric/duodenal bleeding, and pancreatitis) and death occurring within 2 months of treatment were compared between the reversed and the antegrade GDA groups. Results: Ninety-two patients underwent preliminary angiography. Reversed GDA flow was found on angiography in 14.1% of cases; the GDA was not embolised in these patients. The GDA was coiled in 55.7% of patients with antegrade GDA flow to prevent inadvertent dispersal of radioembolic material. There was no increased toxicity related to nontarget dispersal by way of the GDA, or increased early mortality, in patients with reversed GDA flow (P > 0.05). Conclusion: In patients with reversed GDA flow, maintenance of a patent GDA before administration of Y{sup 90} radioembolisation does not increase the risk of toxicity from nontarget dispersal. Therapeutic injection, with careful monitoring to identify early vascular stasis, may be safely performed beyond the origin of the patent GDA. A patent GDA with reversed flow provides forward drive for infused particles and may allow alternative access to the hepatic circulation.

  16. Adsorption of monomers on microspherical structures of thermal heterocomplex molecules from amino ACIDS

    NASA Astrophysics Data System (ADS)

    Honda, Hajime; Sakurazawa, Shigeru; Dekikimura, H.; Imai, Eiichi; Matsuno, Koichiro

    1995-10-01

    The surface of a microspherical structure formed in the aqueous suspension of thermal heterocomplex molecules made by heating aspartic acid and proline can adsorb basic amino acids such as histidine, lysine and arginine. It can also adsorb adenine, cytosine, adenosine and cytidine. Electrostatic interactions acting between those monomers to be adsorbed and the adsorbing surface are responsible for the adsorption.

  17. A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres

    PubMed Central

    Wright, Bernice; Parmar, Nina; Bozec, Laurent; Aguayo, Sebastian D

    2015-01-01

    Poly (lactic-co-glycolic) acid microspheres are amenable to a number of biomedical procedures that support delivery of cells, drugs, peptides or genes. Hydrophilisation or wetting of poly (lactic-co-glycolic) acid are an important pre-requisites for attachment of cells and can be achieved via exposure to plasma oxygen or nitrogen, surface hydrolysis with NaOH or chloric acid, immersion in ethanol and water, or prolonged incubation in phosphate buffered saline or cell culture medium. The aim of this study is to develop a simple method for wetting poly (lactic-co-glycolic) acid microspheres for cell delivery applications. A one-step ethanol immersion process that involved addition of serum-supplemented medium and ethanol to PLGA microspheres over 30 min–24 h is described in the present study. This protocol presents a more efficient methodology than conventional two-step wetting procedures. Attachment of human skeletal myoblasts to poly (lactic-co-glycolic) acid microspheres was dependent on extent of wetting, changes in surface topography mediated by ethanol pre-wetting and serum protein adsorption. Ethanol, at 70% (v/v) and 100%, facilitated similar levels of wetting. Wetting with 35% (v/v) ethanol was only achieved after 24 h. Pre-wetting (over 3 h) with 70% (v/v) ethanol allowed significantly greater (p ≤ 0.01) serum protein adsorption to microspheres than wetting with 35% (v/v) ethanol. On serum protein-loaded microspheres, greater numbers of myoblasts attached to constructs wetted with 70% ethanol than those partially wetted with 35% (v/v) ethanol. Microspheres treated with 70% (v/v) ethanol presented a more rugose surface than those treated with 35% (v/v) ethanol, indicating that more efficient myoblast adhesion to the former may be at least partially attributed to differences in surface structure. We conclude that our novel protocol for pre-wetting poly (lactic-co-glycolic) acid microspheres that incorporates biochemical and structural features

  18. A simple and robust method for pre-wetting poly (lactic-co-glycolic) acid microspheres.

    PubMed

    Wright, Bernice; Parmar, Nina; Bozec, Laurent; Aguayo, Sebastian D; Day, Richard M

    2015-08-01

    Poly (lactic-co-glycolic) acid microspheres are amenable to a number of biomedical procedures that support delivery of cells, drugs, peptides or genes. Hydrophilisation or wetting of poly (lactic-co-glycolic) acid are an important pre-requisites for attachment of cells and can be achieved via exposure to plasma oxygen or nitrogen, surface hydrolysis with NaOH or chloric acid, immersion in ethanol and water, or prolonged incubation in phosphate buffered saline or cell culture medium. The aim of this study is to develop a simple method for wetting poly (lactic-co-glycolic) acid microspheres for cell delivery applications. A one-step ethanol immersion process that involved addition of serum-supplemented medium and ethanol to PLGA microspheres over 30 min-24 h is described in the present study. This protocol presents a more efficient methodology than conventional two-step wetting procedures. Attachment of human skeletal myoblasts to poly (lactic-co-glycolic) acid microspheres was dependent on extent of wetting, changes in surface topography mediated by ethanol pre-wetting and serum protein adsorption. Ethanol, at 70% (v/v) and 100%, facilitated similar levels of wetting. Wetting with 35% (v/v) ethanol was only achieved after 24 h. Pre-wetting (over 3 h) with 70% (v/v) ethanol allowed significantly greater (p ≤ 0.01) serum protein adsorption to microspheres than wetting with 35% (v/v) ethanol. On serum protein-loaded microspheres, greater numbers of myoblasts attached to constructs wetted with 70% ethanol than those partially wetted with 35% (v/v) ethanol. Microspheres treated with 70% (v/v) ethanol presented a more rugose surface than those treated with 35% (v/v) ethanol, indicating that more efficient myoblast adhesion to the former may be at least partially attributed to differences in surface structure. We conclude that our novel protocol for pre-wetting poly (lactic-co-glycolic) acid microspheres that incorporates biochemical and structural features

  19. Effect of interfacial serum proteins on melanoma cell adhesion to biodegradable poly(l-lactic acid) microspheres coated with hydroxyapatite.

    PubMed

    Shinto, Hiroyuki; Hirata, Takuya; Fukasawa, Tomonori; Fujii, Syuji; Maeda, Hayata; Okada, Masahiro; Nakamura, Yoshinobu; Furuzono, Tsutomu

    2013-08-01

    We have measured the interaction forces between a murine melanoma cell and a poly(l-lactic acid) (PLLA) microsphere coated with/without hydroxyapatite (HAp) nanoparticles (i.e., an HAp/PLLA or a bare PLLA microsphere) in a serum-free culture medium, using atomic force microscopy (AFM) with colloid probe technique, in order to investigate how the HAp-nanoparticle coating as well as interfacial serum proteins influence the cell-microsphere adhesion. The cell adhesion force of the HAp/PLLA microspheres was 1.4-fold stronger than that of the bare PLLA microspheres. When the microspheres were pretreated with a culture medium supplemented with 10% fetal bovine serum, the cell adhesion force of the HAp/PLLA microspheres was increased by a factor of 2.1; in contrast, no change was observed in the cell adhesion force of the bare PLLA microspheres before/after the pretreatment. Indeed, the cell adhesion force of the HAp/PLLA was 2.8-fold larger than that of the bare PLLA after the pretreatment. Additionally, we have investigated the effect of interfacial serum proteins on the zeta potentials of these microspheres. On the basis of the obtained results, possible mechanism of cell adhesion to the HAp/PLLA and bare PLLA microspheres in the presence/absence of the interfacial serum proteins is discussed.

  20. Effect of interfacial serum proteins on melanoma cell adhesion to biodegradable poly(l-lactic acid) microspheres coated with hydroxyapatite.

    PubMed

    Shinto, Hiroyuki; Hirata, Takuya; Fukasawa, Tomonori; Fujii, Syuji; Maeda, Hayata; Okada, Masahiro; Nakamura, Yoshinobu; Furuzono, Tsutomu

    2013-08-01

    We have measured the interaction forces between a murine melanoma cell and a poly(l-lactic acid) (PLLA) microsphere coated with/without hydroxyapatite (HAp) nanoparticles (i.e., an HAp/PLLA or a bare PLLA microsphere) in a serum-free culture medium, using atomic force microscopy (AFM) with colloid probe technique, in order to investigate how the HAp-nanoparticle coating as well as interfacial serum proteins influence the cell-microsphere adhesion. The cell adhesion force of the HAp/PLLA microspheres was 1.4-fold stronger than that of the bare PLLA microspheres. When the microspheres were pretreated with a culture medium supplemented with 10% fetal bovine serum, the cell adhesion force of the HAp/PLLA microspheres was increased by a factor of 2.1; in contrast, no change was observed in the cell adhesion force of the bare PLLA microspheres before/after the pretreatment. Indeed, the cell adhesion force of the HAp/PLLA was 2.8-fold larger than that of the bare PLLA after the pretreatment. Additionally, we have investigated the effect of interfacial serum proteins on the zeta potentials of these microspheres. On the basis of the obtained results, possible mechanism of cell adhesion to the HAp/PLLA and bare PLLA microspheres in the presence/absence of the interfacial serum proteins is discussed. PMID:23524077

  1. Preparation of monodisperse aqueous microspheres containing high concentration of l-ascorbic acid by microchannel emulsification.

    PubMed

    Khalid, Nauman; Kobayashi, Isao; Neves, Marcos A; Uemura, Kunihiko; Nakajima, Mitsutoshi; Nabetani, Hiroshi

    2015-01-01

    Monodisperse aqueous microspheres containing high concentrations of l-ascorbic acid with different concentrations of sodium alginate (Na-ALG) and magnesium sulfate (MgSO4) were prepared by using microchannel emulsification (MCE). The continuous phase was water-saturated decane containing a 5% (w/w) hydrophobic emulsifier. The flow rate of the continuous phase was maintained at 10 mL h(-1), whereas the pressure applied to the disperse phase was varied between 3 and 25 kPa. The disperse phase optimized for successfully generating aqueous microspheres included 2% (w/w) Na-ALG and 1% (w/w) MgSO4. At a higher MgSO4 concentration, the generated microspheres resulted in coalescence and subsequent bursting. At a lower MgSO4 concentration, unstable and polydisperse microspheres were obtained. The aqueous microspheres generated from the MCs under optimized conditions had a mean particle diameter (dav) of 14-16 µm and a coefficient of variation (CV) of less than 8% at the disperse phase pressures of 5-15 kPa.

  2. Phase separation behavior of fusidic acid and rifampicin in PLGA microspheres.

    PubMed

    Gilchrist, Samuel E; Rickard, Deborah L; Letchford, Kevin; Needham, David; Burt, Helen M

    2012-05-01

    The purpose of this study was to characterize the phase separation behavior of fusidic acid (FA) and rifampicin (RIF) in poly(d,l-lactic acid-co-glycolic acid) (PLGA) using a model microsphere formulation. To accomplish this, microspheres containing 20% FA with 0%, 5%, 10%, 20%, and 30% RIF and 20% RIF with 30%, 20% 10%, 5%, and 0% FA were prepared by solvent evaporation. Drug-polymer and drug-drug compatibility and miscibility were characterized using laser confocal microscopy, Raman spectroscopy, XRPD, DSC, and real-time video recordings of single-microsphere formation. The encapsulation of FA and RIF alone, or in combination, results in a liquid-liquid phase separation of solvent-and-drug-rich microdomains that are excluded from the polymer bulk during microsphere hardening, resulting in amorphous spherical drug-rich domains within the polymer bulk and on the microsphere surface. FA and RIF phase separate from PLGA at relative droplet volumes of 0.311 ± 0.014 and 0.194 ± 0.000, respectively, predictive of the incompatibility of each drug and PLGA. When coloaded, FA and RIF phase separate in a single event at the relative droplet volume 0.251 ± 0.002, intermediate between each of the monoloaded formulations and dependent on the relative contribution of FA or RIF. The release of FA and RIF from phase-separated microspheres was characterized exclusively by a burst release and was dependent on the phase exclusion of surface drug-rich domains. Phase separation results in coalescence of drug-rich microdroplets and polymer phase exclusion, and it is dependent on the compatibility between FA and RIF and PLGA. FA and RIF are mutually miscible in all proportions as an amorphous glass, and they phase separate from the polymer as such. These drug-rich domains were excluded to the surface of the microspheres, and subsequent release of both drugs from the microspheres was rapid and reflected this surface location.

  3. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    PubMed Central

    Zhao, Qun; Li, Zhi-yue; Zhang, Ze-peng; Mo, Zhou-yun; Chen, Shi-jie; Xiang, Si-yu; Zhang, Qing-shan; Xue, Min

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury. PMID:26604912

  4. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury.

    PubMed

    Zhao, Qun; Li, Zhi-Yue; Zhang, Ze-Peng; Mo, Zhou-Yun; Chen, Shi-Jie; Xiang, Si-Yu; Zhang, Qing-Shan; Xue, Min

    2015-09-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site; their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the microspheres at 300-μm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implantation, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve fibers were observed and distributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  5. Effect of linoleic acid sustained-release microspheres on Microcystis aeruginosa antioxidant enzymes activity and microcystins production and release.

    PubMed

    Ni, Lixiao; Jie, Xiaoting; Wang, Peifang; Li, Shiyin; Wang, Guoxiang; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-02-01

    The objective of this work was to identify the optimal dose range for good anti-algal effect of linoleic acid (LA) sustained-release microspheres and investigate their impact on the antioxidant enzymes (super oxide dismutase, Catalase and Peroxidase) activity changes of Microcystis aeruginosa, as well as the production and release of microcystins (MCs). Based on measured changes in algal cell density and inhibitory ratio (IR), the optimal dose of LA microspheres was 0.3 g L(-1) with over 90% of IR in this study. The Chlorophyll a content and antioxidant enzymes activity in the LA microspheres group decreased markedly until beyond the minimal detection limit after 16 d and 9 d, respectively. In addition, LA microspheres demonstrated no significant impact on the extracellular release of MCs during the culturing period. The amount of intracellular microcystin-LR (MC-LR) per 10(6) algal cells in LA microspheres group was highest among all groups during the whole experimental process. Under the sustained stress of LA released from LA microspheres, the LA microspheres could decrease the production and release of algal toxins. There was no increase in the total amount of MC-LR in the algal cell culture medium. These indicated that LA sustained-release microspheres represent a high degree of ecological safety and their practical applications for the treatment of water undergoing algal blooms need further study.

  6. Polyacrolein microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1987-01-01

    Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

  7. Polyacrolein microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1986-01-01

    Microspheres of acrolein homopolymers and copolymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

  8. Polyacrolein microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1983-01-01

    Microspheres of acrolein homopolymers and co-polymer with hydrophillic comonomers such as methacrylic acid and/or hydroxyethylmethacrylate are prepared by cobalt gamma irradiation of dilute aqueous solutions of the monomers in presence of suspending agents, especially alkyl sulfates such as sodium dodecyl sulfate. Amine or hydroxyl modification is achieved by forming adducts with diamines or alkanol amines. Carboxyl modification is effected by oxidation with peroxides. Pharmaceuticals or other aldehyde reactive materials can be coupled to the microspheres. The microspheres directly form antibody adducts without agglomeration.

  9. Investigation of emulsified, acid and acid-alkali catalyzed mesoporous bioactive glass microspheres for bone regeneration and drug delivery.

    PubMed

    Miao, Guohou; Chen, Xiaofeng; Dong, Hua; Fang, Liming; Mao, Cong; Li, Yuli; Li, Zhengmao; Hu, Qing

    2013-10-01

    Acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were successfully synthesized via combination of sol-gel and water-in-oil (W/O) micro-emulsion methods. The structural, morphological and textural properties of mesoporous bioactive glass microspheres (MBGMs) were characterized by various techniques. Results show that both MBGMs-A and MBGMs-B exhibit regularly spherical shape but with different internal porous structures, i.e., a dense microstructure for MBGMs-A and internally porous structure for MBGMs-B. (29)Si NMR data reveal that MGBMs have low polymerization degree of silica network. The in vitro bioactivity tests indicate that the apatite formation rate of MBGMs-B was faster than that of MBGMs-A after soaking in simulated body fluid (SBF) solution. Furthermore, the two kinds of MBGMs have similar storage capacity of alendronate (AL), and the release behaviors of AL could be controlled due to their unique porous structure. In conclusion, the microspheres are shown to be promising candidates as bone-related drug carriers and filling materials of composite scaffold for bone repair.

  10. Investigation of emulsified, acid and acid-alkali catalyzed mesoporous bioactive glass microspheres for bone regeneration and drug delivery.

    PubMed

    Miao, Guohou; Chen, Xiaofeng; Dong, Hua; Fang, Liming; Mao, Cong; Li, Yuli; Li, Zhengmao; Hu, Qing

    2013-10-01

    Acid-catalyzed mesoporous bioactive glass microspheres (MBGMs-A) and acid-alkali co-catalyzed mesoporous bioactive glass microspheres (MBGMs-B) were successfully synthesized via combination of sol-gel and water-in-oil (W/O) micro-emulsion methods. The structural, morphological and textural properties of mesoporous bioactive glass microspheres (MBGMs) were characterized by various techniques. Results show that both MBGMs-A and MBGMs-B exhibit regularly spherical shape but with different internal porous structures, i.e., a dense microstructure for MBGMs-A and internally porous structure for MBGMs-B. (29)Si NMR data reveal that MGBMs have low polymerization degree of silica network. The in vitro bioactivity tests indicate that the apatite formation rate of MBGMs-B was faster than that of MBGMs-A after soaking in simulated body fluid (SBF) solution. Furthermore, the two kinds of MBGMs have similar storage capacity of alendronate (AL), and the release behaviors of AL could be controlled due to their unique porous structure. In conclusion, the microspheres are shown to be promising candidates as bone-related drug carriers and filling materials of composite scaffold for bone repair. PMID:23910338

  11. Formulation of salicylate-based poly(anhydride-ester) microspheres for short- and long-term salicylic acid delivery

    PubMed Central

    Rosario-Meléndez, Roselin; Ouimet, Michelle A.; Uhrich, Kathryn E.

    2013-01-01

    The formulation of salicylate-based poly(anhydride-ester) (PAE) microspheres was optimized by altering polymer concentration and homogenization speed to improve the overall morphology. The microspheres were prepared using three salicylate-based PAEs with different chemical compositions comprised of either a heteroatomic, linear aliphatic, or branched aliphatic moiety. These PAEs broadened the range of complete salicylic acid release to now include days, weeks and months. The molecular weight (Mw), polydispersity index (PDI) and glass transition temperature (Tg) of the formulated polymers were compared to the unformulated polymers. In general, the Mw and PDI exhibited decreased and increased values, respectively, after formulation, whereas the Tg changes did not follow a specific trend. Microsphere size and morphology were determined using scanning electron microscopy. These microspheres exhibited smooth surfaces, no aggregation, and size distributions ranging from 2-34 m in diameter. In vitro release studies of the chemically incorporated salicylic acid displayed widely tunable release profiles. PMID:23420391

  12. Hyaluronic acid as an internal phase additive to obtain ofloxacin/PLGA microsphere by double emulsion method.

    PubMed

    Wu, Gang; Chen, Long; Li, Hong; Wang, Ying-jun

    2014-01-01

    Hyaluronic acid (HA) was used as an internal phase additive to improve the loading efficiency of ofloxacin, a hydrophilic drug encapsulated by hydrophobic polylactic-co-glycolic acid (PLGA) materials, through a double emulsion (water-in-oil-in-water) solvent extraction/evaporation method. Results from laser distribution analysis show that polyelectrolyte additives have low impact on the average particle size and distribution of the microspheres. The negatively charged HA increases the drug loading efficiency as well as the amount of HA in microspheres. Burst release can be observed in the groups with the polyelectrolyte additives. The release rate decreases with the amount of HA inside the microspheres in all negatively charged polyelectrolyte-added microsphere groups.

  13. Development of lovastatin-loaded poly(lactic acid) microspheres for sustained oral delivery: in vitro and ex vivo evaluation

    PubMed Central

    Guan, Qigang; Chen, Wei; Hu, Xianming

    2015-01-01

    Background A novel lovastatin (LVT)-loaded poly(lactic acid) microsphere suitable for oral administration was developed in this study, and in vitro and in vivo characteristics were evaluated. Methods The designed microspheres were obtained by an improved emulsion-solvent evaporation method. The morphological examination, particle size, encapsulation ratio, drug loading, and in vitro release were characterized. Pharmacokinetics studies were used to show that microspheres possess more advantages than the conventional formulations. Results By using the emulsion-solvent evaporation method, it was simple to prepare microspheres and easy to scale up production. The morphology of formed microspheres showed a spherical shape with a smooth surface, without any particle aggregation. Mean size of the microspheres was 2.65±0.69 μm; the encapsulation efficiency was 92.5%±3.6%, and drug loading was 16.7%±2.1%. In vitro release indicated that the LVT microspheres had a well-sustained release efficacy, and ex vivo studies showed that after LVT was loaded to microspheres, the area under the plasma concentration-time curve from zero to the last measurable plasma concentration point and the extrapolation to time infinity increased significantly, which represented 2.63-fold and 2.49-fold increases, respectively, compared to suspensions. The rate of ex vivo clearance was significantly reduced. Conclusion This research proved that poly(lactic acid) microspheres can significantly prolong the drug circulation time in vivo and can also significantly increase the relative bioavailability of the drug. PMID:25709403

  14. Reaction kinetics of photocatalytic degradation of sulfosalicylic acid using TiO2 microspheres.

    PubMed

    Wang, Chuan; Zhang, Xianghua; Liu, Hong; Li, Xiangzhong; Li, Wenzhao; Xu, Hengyong

    2009-04-30

    The photocatalytic (PC) degradation kinetics of sulfosalicylic acid (SSA) at different pH using TiO2 microspheres were elucidated by modeling. The resultant model had special consideration of adsorption and pH. The adsorption isotherms showed that the LC/MS(2)-identified intermediates were weakly adsorbed on the TiO2 microspheres, thus their adsorption was neglected in the modeling. By contrast, the SSA was significantly adsorbed, thus its adsorption retained as an item in the model. Consequently, a non-first-order model was obtained. Through the modeling, it was elucidated that the reaction rate increased non-linearly with the SSA adsorption equilibrium constant. Meanwhile, it was elucidated that a pH increase favored the hydroxyl radical production to accelerate the SSA degradation, while impeded the SSA adsorption to slower it, hence a neutral pH caused the fastest SSA degradation. PMID:18762374

  15. Protective colloids and polylactic acid co-affecting the polymorphic crystal forms and crystallinity of indomethacin encapsulated in microspheres.

    PubMed

    Lin, S Y; Chen, K S; Teng, H H

    1999-01-01

    The co-effect of protective colloids and polylactic acid (PLA) on the polymorphic crystal forms and crystallinity of indomethacin (IMC) in IMC-loaded PLA microspheres was investigated with differential scanning calorimetry, infrared spectroscopy and x-ray diffractometry, to evaluate the polymorphic crystal forms and crystallinity of IMC encapsulated in PLA microspheres. The surfactant, sodium dodecyl sulphate (SDS), was also used as a dispersing agent. The results indicate that the polymorphism and crystallinity of IMC encapsulated in IMC-loaded PLA microspheres was dependent on the type of protective colloid and PLA used. The amorphous state and alpha-form of IMC were found in the IMC-loaded PLA microspheres prepared using polysaccharide (pectin or beta-cyclodextrin) as a protective colloid or SDS as a dispersing agent. However, the amorphous and methylene chloride solvate of IMC seemed to exist in the IMC-loaded PLA microspheres prepared with the proteins (gelatin or albumin), synthetic cellulose derivative (methyl cellulose or hydroxylpropyl methylcellulose) or the synthetic nonionic polymer (polyvinyl alcohol, polyvinyl pyrrolidone or biosoluble polymer) as a protective colloid. PLA was found to express a certain crystallinity in microspheres and not be affected by the protective colloids, but it played a more important role in influencing the crystallization of IMC during microencapsulation than the protective colloids. No interaction occurred in the physical mixture of IMC and PLA, nor in the IMC-loaded PLA microspheres.

  16. Interfacial Fast Release Layer in Monodisperse Poly (lactic-co-glycolic acid) Microspheres Accelerates the Drug Release.

    PubMed

    Wu, Jun; Zhao, Xiaoli; Yeung, Kelvin W K; To, Michael K T

    2016-01-01

    Understanding microstructural evolutions of drug delivery devices during drug release process is essential for revealing the drug release mechanisms and controlling the drug release profiles. In this study, monodisperse poly (lactic-co-glycolic acid) microspheres in different diameters were fabricated by microfluidics in order to find out the relationships between the microstructural evolutions and the drug release profiles. It was found that poly (lactic-co-glycolic acid) microspheres underwent significant size expansion which took place from the periphery to the center, resulting in the formation of interfacial fast release layers. At the same time, inner pores were created and the diffusion rate was increased so that the early stage drug release was accelerated. Due to the different expansion rates, small poly (lactic-co-glycolic acid) microspheres tendered to follow homogeneous drug release while large poly (lactic-co-glycolic acid) microspheres tendered to follow heterogeneous drug release. This study suggests that the size expansion and the occurrence of interfacial fast release layer were important mechanisms for early stage drug release of poly (lactic-co-glycolic acid) microspheres.

  17. Tunable delivery of niflumic acid from resorbable embolization microspheres for uterine fibroid embolization.

    PubMed

    Bédouet, Laurent; Moine, Laurence; Servais, Emeline; Beilvert, Anne; Labarre, Denis; Laurent, Alexandre

    2016-09-10

    Uterine arteries embolization (UAE) is a recent technique that aims, by means of particles injected percutaneously, to stifle fibroids (leiomyomas). This treatment is non-invasive, compared with uterine ablation, but generates pelvic pain for a few days. A strategy to reduce the post-embolization pain would be to use calibrated embolization microspheres preloaded with a non-steroidal inflammatory drug (NSAID). In this study, we first compared four drugs, all active at low concentration on cyclooxygenase-2, i.e. ketoprofen, sodium diclofenac, flurbiprofen and niflumic acid (NFA), for their capacity to be loaded on resorbable embolization microspheres (REM) 500-700μm. NFA had the highest capacity of loading (5mg/mL) on resorbable microspheres. Then, we evaluated in vitro the NFA release profiles from REM having various degradation times of one, two or five days. NFA release was biphasic, with an initial burst (about 60% of the loading) followed by a sustained release that correlated significantly to REM's hydrolysis (rho=0.761, p<0.0001). For each group of beads, the size distribution was not modified by the loading of NFA and their delivery through microcatheter was not impaired by the drug. NFA eluted from REM inhibited the synthesis of prostaglandin E2 from rabbit uterus explants. In summary, NFA is loadable on REM in significant amount and its delivery can be tuned according to the degradation rate of REM to provide an antalgic effect for a few days after UAE. PMID:27374196

  18. pH-independent controlled-release microspheres using polyglycerol esters of fatty acids.

    PubMed

    Akiyama, Y; Yoshioka, M; Horibe, H; Hirai, S; Kitamori, N; Toguchi, H

    1994-11-01

    The release of a drug having low solubility in a certain pH range from controlled-release microspheres using tetraglycerol pentastearate and tetraglycerol monostearate in combination as the matrix base showed pH dependence. Trepibutone, an acidic drug having lower solubility in an acidic medium, was released pH-independently from the microspheres which incorporated magnesium oxide, a solid base. It might have resulted from the pH inside the matrix being kept in an optimum range for drug release due to the incorporation of a solid base. On the other hand, the addition of water soluble acidic or basic excipients was ineffective to achieve pH-independent release. For papaverine, a basic drug, pH-independent drug-release characteristics could be achieved by adding Eudragit L100-55, an enteric polymer. It is thought that the enteric polymer increased the pores for drug release by dissolving in a higher pH range, where the solubility of papaverine is low, and thereby made the release pH-independent. Further, selecting a polyglycerol ester of a fatty acid with an appropriate hydrophile-lipophile balance as the matrix could yield a drug with the desired release rate at any pH.

  19. Boronic acid-functionalized core-shell-shell magnetic composite microspheres for the selective enrichment of glycoprotein.

    PubMed

    Pan, Miaorong; Sun, Yangfei; Zheng, Jin; Yang, Wuli

    2013-09-11

    In this work, core-shell-shell-structured boronic acid-functionalized magnetic composite microspheres Fe3O4@SiO2@poly (methyl methacrylate-co-4-vinylphenylbornoic acid) (Fe3O4@SiO2@P(MMA-co-VPBA)) with a uniform size and fine morphology were synthesized. Here, Fe3O4 magnetic particles were prepared by a solvothermal reaction, whereas the Fe3O4@SiO2 microspheres with a core-shell structure were obtained by a sol-gel process. 3-(Trimethoxysilyl) propyl methacrylate (MPS)-modified Fe3O4@SiO2 was used as the seed in the emulsion polymerization of MMA and VPBA to form the core-shell-shell-structured magnetic composite microspheres. As the boronic acid groups on the surface of Fe3O4@SiO2@P(MMA-co-VPBA) could form tight yet reversible covalent bonds with the cis-1,2-diols groups of glycoproteins, the magnetic composite microspheres were applied to enrich a standard glycoprotein, horseradish peroxidase (HRP), and the results demonstrated that the composite microspheres have a higher affinity for the glycoproteins in the presence of the nonglycoprotein bovine serum albumin (BSA) over HRP. Additionally, different monomer mole ratios of MMA/VPBA were studied, and the results implied that using MMA as the major monomer could reduce the amount of VPBA with a similar glycoprotein enrichment efficiency but a lower cost. PMID:23924282

  20. Functionalized antibiofilm thin coatings based on PLA-PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE

    NASA Astrophysics Data System (ADS)

    Grumezescu, Valentina; Socol, Gabriel; Grumezescu, Alexandru Mihai; Holban, Alina Maria; Ficai, Anton; Truşcǎ, Roxana; Bleotu, Coralia; Balaure, Paul Cǎtǎlin; Cristescu, Rodica; Chifiriuc, Mariana Carmen

    2014-05-01

    We report the fabrication of thin coatings of PLA-PVA microspheres loaded with usnic acid by matrix assisted pulsed laser evaporation (MAPLE) onto Ti substrate. The obtained coatings have been physico-chemically characterized by scanning electron microscopy (SEM) and infrared microscopy (IRM). In vitro biological assays have been performed in order to evaluate the influence of fabricated microsphere thin coatings on the Staphylococcus aureus biofilm development as well as their biocompatibility. SEM micrographs have revealed a uniform morphology of thin coatings, while IRM investigations have proved both the homogeneity and functional groups integrity of prepared thin coatings. The obtained microsphere-based thin coatings have proved to be efficient vehicles for usnic acid natural compound with antibiofilm activity, as demonstrated by the inhibitory activity on S. aureus mature biofilm development, opening new perspectives for the prevention and therapy associated to biofilm related infections.

  1. Lead recovery and glass microspheres synthesis from waste CRT funnel glasses through carbon thermal reduction enhanced acid leaching process.

    PubMed

    Mingfei, Xing; Yaping, Wang; Jun, Li; Hua, Xu

    2016-03-15

    In this study, a novel process for detoxification and reutilization of waste cathode ray tube (CRT) funnel glass was developed by carbon thermal reduction enhanced acid leaching process. The key to this process is removal of lead from the CRT funnel glass and synchronous preparation of glass microspheres. Carbon powder was used as an isolation agent and a reducing agent. Under the isolation of the carbon powder, the funnel glass powder was sintered into glass microspheres. In thermal reduction, PbO in the funnel glass was first reduced to elemental Pb by carbon monoxide and then located on the surface of glass microspheres which can be removed easily by acid leaching. Experimental results showed that temperature, carbon adding amount and holding time were the major parameters that controlled lead removal rate. The maximum lead removal rate was 94.80% and glass microspheres that measured 0.73-14.74μm were obtained successfully by setting the temperature, carbon adding amount and holding time at 1200°C, 10% and 30min, respectively. The prepared glass microspheres may be used as fillers in polymer materials and abrasive materials, among others. Accordingly, this study proposed a practical and economical process for detoxification and recycling of waste lead-containing glass. PMID:26642446

  2. Polymeric microspheres

    DOEpatents

    Walt, David R.; Mandal, Tarun K.; Fleming, Michael S.

    2004-04-13

    The invention features core-shell microsphere compositions, hollow polymeric microspheres, and methods for making the microspheres. The microspheres are characterized as having a polymeric shell with consistent shell thickness.

  3. Long-term toxicity of holmium-loaded poly(L-lactic acid) microspheres in rats.

    PubMed

    Zielhuis, Sander W; Nijsen, J Frank W; Seppenwoolde, Jan-Henry; Bakker, Chris J G; Krijger, Gerard C; Dullens, Hub F J; Zonnenberg, Bernard A; van Rijk, Peter P; Hennink, Wim E; van het Schip, Alfred D

    2007-11-01

    The aim of this study was to get insight into the toxic effects of holmium-166-loaded poly(L-lactic acid) microspheres (Ho-PLLA-MS) which have very interesting features for treatment of liver malignancies. Acute, mid- and long-term effects were studied in healthy Wistar rats by evaluating clinical, biochemical and tissue response. Rats were divided into four treatment groups: sham, decayed neutron-irradiated Ho-PLLA-MS, non-irradiated Ho-PLLA-MS and PLLA-MS. After implantation of the microspheres into the liver of the rats, the animals were monitored (body weight, temperature and liver enzymes) for a period of 14-18 months. Some of the rats that received previously neutron-irradiated Ho-PLLA-MS were periodically scanned with magnetic resonance imaging (MRI) to see if holmium was released from the microspheres. After sacrifice, the liver tissue was histologically evaluated. Bone tissue was subjected to neutron-activation analysis in order to examine whether accumulation of released holmium in the bone had occurred. No measurable clinical and biochemical toxic effects were observed in any of the treatment groups. Furthermore, histological analyses of liver tissue samples only showed signs of a slight chronic inflammation and no significant differences in the tissue reaction between rats of the different treatment groups could be observed. The non-irradiated PLLA-MS and Ho-PLLA-MS stayed intact during the study. In contrast, 14 months after administration, the neutron-irradiated Ho-PLLA-MS was not completely spherical anymore, indicating that degradation had started. However, the holmium loading had not been released as was illustrated with MRI and affirmed by neutron-activation analysis of bone tissue. In conclusion, neutron-irradiated Ho-PLLA-MS does not provoke any toxic reaction and can be applied safely in vivo.

  4. Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug.

    PubMed

    Li, Rongrong; Feng, Fuli; Wang, Yinsong; Yang, Xiaoying; Yang, Xinlin; Yang, Victor C

    2014-09-01

    The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine/poly(N-isopropylacrylamide-co-glycidyl methacrylate-co-N,N-bis(acryloyl)cystamine) microspheres were prepared by a two-stage distillation-precipitation polymerization with subsequent surface modification with FA. The microspheres were characterized by transmission electron microscopy, dynamical light scattering, Fourier-transform infrared spectra, UV-vis spectra and elemental analysis. The degradation of the functional microspheres could be triggered by a reductive reagent, such as glutathione, due to presence of BAC crosslinker. The drug-loaded microspheres exhibited a pH/temperature/redox multi-stimuli responsive drug release character for doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently loaded into the microspheres with a high loading capacity of 208.0% and an encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that the FA-conjugated microspheres could deliver Dox into MCF-7 cells more efficiently than the microspheres without functionalization of FA. Furthermore, WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells even at a high concentration of 2000 μg mL(-1). The resultant microsphere may be a promising vector for delivery of anti-cancer drugs as it exhibits a low cytotoxicity and degradability, precise molecular targeting property and multi-stimuli responsively controlled drug release. PMID:24935187

  5. Preparation of Lung-Targeting, Emodin-Loaded Polylactic Acid Microspheres and Their Properties

    PubMed Central

    Chen, Xiaohong; Yang, Zifeng; Sun, Renshan; Mo, Ziyao; Jin, Guangyao; Wei, Fenghuan; Hu, Jianmin; Guan, Wenda; Zhong, Nanshan

    2014-01-01

    Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has been identified to have the potential to improve lung fibrosis and lung cancer. To avoid the liver and kidney toxicities and the fast metabolism of emodin, emodin-loaded polylactic acid microspheres (ED-PLA-MS) were prepared and their characteristics were studied. ED-PLA-MS were prepared by the organic phase dispersion-solvent diffusion method. By applying an orthogonal design, our results indicated that the optimal formulation was 12 mg/mL PLA, 0.5% gelatin, and an organic phase:glycerol ratio of 1:20. Using the optimal experimental conditions, the drug loading and encapsulation efficiencies were (19.0 ± 1.8)% and (62.2 ± 2.6)%, respectively. The average particle size was 9.7 ± 0.7 μm. In vitro studies indicated that the ED-PLA-MS demonstrated a well-sustained release efficacy. The microspheres delivered emodin, primarily to the lungs of mice, upon intravenous injection. It was also detected by microscopy that partial lung inflammation was observed in lung tissues and no pathological changes were found in other tissues of the ED-PLA-MS-treated animals. These results suggested that ED-PLA-MS are of potential value in treating lung diseases in animals. PMID:24733070

  6. Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

    PubMed

    Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

    2006-12-11

    In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection. PMID:17045253

  7. Designing improved poly lactic-co-glycolic acid microspheres for a malarial vaccine: incorporation of alginate and polyinosinic-polycytidilic acid.

    PubMed

    Salvador, Aiala; Igartua, Manoli; Hernández, Rosa María; Pedraz, José Luis

    2014-01-01

    Vaccination using proteins and peptides is currently gaining importance. One of the major drawbacks of this approach is the lack of an efficient immune response when the antigens are administered without adjuvants. In this study, we have taken the advantage of a combined adjuvant system in order to improve the immunogenicity of the SPf66 malarial antigen. For that purpose, we have combined poly (lactic-co-glycolic) acid microspheres, alginate, and polyinosinic polycytidilic acid. Our results show that microspheres can enhance the IgG production obtained with Freund's complete adjuvant. We have attributed this improvement to the presence of polyinosinic polycytidilic acid, since formulations comprising this adjuvant overcame the immune response from the others. In addition, our microspheres produced both IgG1 and IgG2a, leading to mixed Th1/Th2 activation, optimal for malaria vaccination. In conclusion, we have designed a preliminary formulation with a high potential for the treatment of malaria.

  8. Facile one-pot preparation and functionalization of luminescent chitosan-poly(methacrylic acid) microspheres based on polymer monomer pairs

    NASA Astrophysics Data System (ADS)

    Guo, Jia; Wang, Changchun; Mao, Weiyong; Yang, Wuli; Liu, Changjia; Chen, Jiyao

    2008-08-01

    In this paper, we present a facile and robust approach to synthesize multifunctional organic/inorganic composite microspheres with chitosan-poly(methacrylic acid) (CS-PMAA) shells and cadmium tellurium/iron oxide nanoparticle cores. Due to the strong electrostatic interaction between the negatively charged nanoparticles and the protonated CS polymers, the CS/nanoparticle complexes were utilized as templates for the subsequent polymerization of methacrylic acid. The resulting composite microspheres with luminescence and magnetic properties have regular morphologies and narrow size distributions. In contrast to previous reports, this route was based on a one-pot strategy without the aid of surfactants, organic solvent, or polymerizable ligands in aqueous solution. The encapsulated CdTe semiconductor nanocrystals inside the microspheres exhibited strong and stable photoluminescence properties in the pH range 5.0-11.0. When the pH was adjusted below 4, the photoluminescence decreased sharply and even quenched completely. However, the weakened fluorescence emission could be recovered to some degree upon an increase of pH above 5. Additionally, when both Fe3O4 and CdTe nanoparticles were encapsulated within CS-PMAA microspheres, the magnetic content of the microspheres could be efficiently controlled by tuning the feeding molar ratio of MAA monomers and glucosamine units of CS. From the preliminary attempts, it was found that the multifunctional microspheres as imaging agents could improve the rate and extent of cellular uptake under short-term exposure to an applied magnetic field, and so exhibit a great potential as bioactive molecule carriers.

  9. Mandelic acid chiral separation utilizing a two-phase partitioning bioreactor built by polysulfone microspheres and immobilized enzymes.

    PubMed

    Wang, Xinyu; Cui, Yanjun; Chen, Xia; Zhu, Hao; Zhu, Weiwei; Li, Yanfeng

    2015-03-01

    A novel two-phase partitioning bioreactor (TPPB) modified by polysulfone (PSF) microspheres and immobilized enzyme (novozym-435) was formed, and the resulting TPPB was applied into mandelic acid chiral separation. The PSF microspheres containing n-hexanol (named PSF/hexanol microspheres) was prepared by using the phase inversion method, which was used as the organic phase. Meanwhile, the immobilized enzyme novozym-435 was used as a biocatalyst. The water phase was composed of the phosphate buffer solution (PBS). (R, S)-Methyl mandelate was selected as the substrate to study enzymatic properties. Different reaction factors have been researched, such as pH, reaction time, temperature and the quantity of biocatalyst and PSF/hexanol microspheres added in. Finally, (S)-mandelic acid was obtained with an 80 % optical purity after 24 h in the two-phase partitioning bioreactor. The enantiomeric excess (eep) values were very low in the water phase, in which the highest eep value was only 46 %. The eep of the two-phase partitioning bioreactor had been enhanced more obviously than that catalyzed in the water phase.

  10. Magnetically directed poly(lactic acid) [sup 90]Y-microspheres: Novel agents for targeted intracavitary radiotherapy

    SciTech Connect

    Haefeli, U.O.; Sweeney, S.M.; Beresford, B.A.; Sim, E.H.; Macklis, R.M. . Joint Center for Radiation Therapy)

    1994-08-01

    High energy [beta]-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. The authors developed as carriers for the ionic form of [sup 90]Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe[sub 3]O[sub 4] which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10--40 [mu]m MMS were radiochemically loaded to high specific activity with [sup 90]Y at a pH of 5.7. Stability studies showed that approximately 95% of added [sup 90]Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. The authors are currently optimizing this system for use in the treatment of neoplastic meningitis.

  11. Preparing Poly (Lactic-co-Glycolic Acid) (PLGA) Microspheres Containing Lysozyme-Zinc Precipitate Using a Modified Double Emulsion Method

    PubMed Central

    Nafissi Varcheh, Nastaran; Luginbuehl, Vera; Aboofazeli, Reza; Peter Merkle, Hans

    2011-01-01

    Lysozyme, as a model protein, was precipitated through the formation of protein-Zn complex to micronize for subsequent encapsulation within poly (lactic-co-glycolic acid) (PLGA) microspheres. Various parameters, including pH, type and concentration of added salts and protein concentration, were modified to optimize the yield of protein complexation and precipitation. The resulting protein particles (lysozyme-Zn complex as a freshly prepared suspension or a freeze-dried solid) were then loaded into PLGA (Resomer® 503H) microspheres, using a double emulsion technique and microspheres encapsulation efficiency and their sizes were determined. It was observed that salt type could significantly influence the magnitude of protein complexation. At the same conditions, zinc chloride was found to be more successful in producing pelletizable lysozyme. Generally, higher concentrations of protein solution led also to the higher yields of complexation and at the optimum conditions, the percentage of pelletizable lysozyme reached to 80%. Taking advantage of this procedure, a modified technique for preparation of protein-loaded PLGA microspheres was established, although it is also expected that this technique increases the protein drugs stabilization during the encapsulation process. PMID:24250344

  12. Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

    PubMed

    Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

    2015-01-01

    Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture. PMID:25265058

  13. Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

    PubMed

    Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

    2015-01-01

    Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture.

  14. Comparative evaluation of polymeric and waxy microspheres for combined colon delivery of ascorbic acid and ketoprofen.

    PubMed

    Maestrelli, F; Zerrouk, N; Cirri, M; Mura, P

    2015-05-15

    The goal of this work was to combine the ketoprofen anti-inflammatory effect with the ascorbic acid antioxidant properties for a more efficient treatment of colonic pathologies. With this aim, microspheres (MS) based on both waxy materials (ceresine, Precirol(®) and Compritol(®)) or hydrophilic biopolymers (pectine, alginate and chitosan) loaded with the two drugs were developed, physicochemically characterized and compared in terms of entrapment efficiency, in vitro release profiles, potential toxicity and drug permeation properties across the Caco-2 cell line. Waxy MS revealed an high encapsulation efficiency of ketoprofen but a not detectable entrapment of ascorbic acid, while polymeric MS showed a good entrapment efficiency of both drugs. All MS need a gastro-resistant coating, to avoid any premature release of the drugs. Ketoprofen release rate from polymeric matrices was clearly higher than from the waxy ones. In contrast, the ASC release rate was higher, due to its high hydro-solubility. Cytotoxicity studies revealed the safety of all the formulations. Transport studies showed that the ketoprofen apparent permeability increased, when formulated with the different MS. In conclusion, only polymeric MS enabled an efficient double encapsulation of both the hydrophilic and lipophilic drugs, and, in addition, presented higher drug release rate and stronger enhancer properties.

  15. Copolymeric hexyl acrylate-methacrylic acid microspheres - surface vs. bulk reactive carboxyl groups. Coulometric and colorimetric determination and analytical applications for heterogeneous microtitration.

    PubMed

    Stelmach, Emilia; Maksymiuk, Krzysztof; Michalska, Agata

    2016-10-01

    Copolymeric acrylate microspheres were prepared from hexyl acrylate using different amounts of methacrylic acid, resulting in a series of microspheres of gradually changing properties. The distribution of carboxyl groups - between surface and bulk of microspheres was evaluated. Bulk reactive carboxyl groups were determined using reverse coulometric titration with H(+) ions, following hydroxide ions have been generated and allowed to react with microspheres in the first step. It was found that the number of reactive carboxyl groups available in copolymeric microspheres is lower compared to number of methacrylic acid units used for polymerization process. Moreover, there is correlation between the number of groups introduced and found to be reactive in microspheres. On the other hand, the number of surface reactive groups was proportional to the number of groups introduced in course of polymerization. Thus, the surface reactive groups can be used as reagent, in novel heterogeneous microtitration procedure, in which a constant number of microspheres of different carboxyl groups contents is introduced to the sample to react with the analyte. The applicability of novel proposed method was tested on the example of Ni(2+) determination. PMID:27474305

  16. Investigating the use of porous, hollow glass microspheres in positive lead acid battery plates

    NASA Astrophysics Data System (ADS)

    Sorge, Matthew; Bean, Thomas; Woodland, Travis; Canning, John; Cheng, I. Frank; Edwards, Dean B.

    2014-11-01

    Porous, hollow, glass microspheres (PHGMs) can be used to increase porosity in lead acid battery electrodes to improve the battery's power and energy performance at higher discharge rates. As reported in this paper, the PHGM additives did improve electrolyte storage and porosity in the electrodes. However, the nonconductive PHGMs do reduce the critical volume fraction (CVF) of the electrodes as predicted from conductivity models. The increase in electrode performance due to increased porosity may therefore be partially offset by the drop in capacity due to a lower critical volume fraction. Empirical equations are developed that relate the CFV and porosity of an electrode to the amount, size, and porosity of the additives in that electrode. The porosity estimates made from the empirical equations compare favorably with the experimental data from plates fabricated with these additives. The performance of electrodes with additives is estimated from computer models using the electrode's CVF and porosity as provided by the equations. Tests were performed on plates having volume loadings of PHGMs from 11% to 44% of total solids in positive electrodes to determine their effect on active material utilizations. The results from these discharge tests are reported and compared with theoretical models.

  17. Uniform magnetic core/shell microspheres functionalized with Ni2+-iminodiacetic acid for one step purification and immobilization of his-tagged enzymes.

    PubMed

    Zhang, Yuting; Yang, Yongkun; Ma, Wanfu; Guo, Jia; Lin, Yao; Wang, Changchun

    2013-04-10

    A facile approach has been developed to synthesize Fe3O4/PMG (poly (N,N'-methylenebisacrylamide-co-glycidyl methacrylate)) core/shell microspheres using distillation-precipitation polymerization. Treating PMG shell with iminodiacetic acid (IDA) and Ni2+ yields composite microspheres of Fe3O4/PMG/IDA-Ni2+. The Ni2+ ions loaded on the surface of microspheres provide abundant docking sites for immobilization of histidine-tagged proteins. The high saturation magnetization of Fe3O4/PMG (23 emu/g), determined by vibrating sample magnetometer (VSM), allows an easy separation of the microspheres from solution under an external magnetic field. The composite microspheres were used to purify two His-tagged cellulolytic enzymes (Cel48F and Cel9G) directly from crude cell lysates with high binding affinity, capacity, and specificity. The microspheres can be recycled for many times without significant loss of binding capacity to enzymes. The immobilized enzymes on the surface of microspheres well retain their biological activities in degradation of cellulose. These materials show great potential in the biomedical and biotechnological applications that require low-cost purification of recombinant proteins and instant enzyme immobilization at an industrial scale. PMID:23470159

  18. β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release.

    PubMed

    Song, Xia; Song, San-Kong; Zhao, Pei; Wei, Li-Ming; Jiao, Hai-Sheng

    2013-01-01

    A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.

  19. Stabilization and immune response of HBsAg encapsulated within poly(lactic-co-glycolic acid) microspheres using HSA as a stabilizer.

    PubMed

    Xu, Wenjuan; He, Jintian; Wu, Guanghao; Xiong, Fangfang; Du, Huijuan; Wang, Gaizhen

    2015-12-30

    The aim of this study was to prepare poly(lactic-co-glycolic acid) (PLGA) microspheres containing hepatitis B virus surface antigen (HBsAg) using human serum albumin (HSA) as a stabilizer. Lyophilization and emulsification of HBsAg solution with dichloromethane caused a considerable loss of HBsAg antigenicity. Thus, the effects of HSA and trehalose on HBsAg recovery during lyophilization and emulsification were investigated. Adding HSA to HBsAg solutions significantly improved antigen recovery to >90% during lyophilization and emulsification. The effects of co-encapsulated HSA on the characteristics of the PLGA microspheres and stability of HBsAg released from the microspheres were also investigated. The in vitro release test showed that HBsAg was released from the PLGA microspheres continuously over seventy days. A large amount of released HBsAg was inactive without co-encapsulation of HSA. On the contrary, with HSA co-encapsulation, the released HBsAg retained approximately 90% of its antigenicity. The single injection of the HBsAg-HSA-loaded PLGA microspheres in rats resulted in higher anti-HBsAg IgG and Th1 cytokine levels than the single injection of the HBsAg-loaded microspheres or two injections of the conventional aluminum-adjuvanted HBsAg vaccine. Based on these findings, the HBsAg-HSA-loaded PLGA microspheres could be an effective carrier for HBsAg and form a promising depot system.

  20. Metabolism of proteinoid microspheres

    NASA Technical Reports Server (NTRS)

    Nakashima, T.; Fox, S. W. (Principal Investigator)

    1987-01-01

    The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolysis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

  1. Metabolism of proteinoid microspheres

    NASA Technical Reports Server (NTRS)

    Nakashima, T.; Fox, S. W. (Principal Investigator)

    1987-01-01

    The literature of metabolism in proteinoids and proteinoid microspheres is reviewed and criticized from a biochemical and experimental point of view. Closely related literature is also reviewed in order to understand the function of proteinoids and proteinoid microspheres. Proteinoids or proteinoid microspheres have many activities. Esterolyis, decarboxylation, amination, deamination, and oxidoreduction are catabolic enzyme activities. The formation of ATP, peptides or oligonucleotides is synthetic enzyme activities. Additional activities are hormonal and inhibitory. Selective formation of peptides is an activity of nucleoproteinoid microspheres; these are a model for ribosomes. Mechanisms of peptide and oligonucleotide syntheses from amino acids and nucleotide triphosphate by proteinoid microspheres are tentatively proposed as an integrative consequence of reviewing the literature.

  2. Simultaneous removal of acid green 25 and mercury ions from aqueous solutions using glutamine modified chitosan magnetic composite microspheres.

    PubMed

    Tao, Xue; Li, Kun; Yan, Han; Yang, Hu; Li, Aimin

    2016-02-01

    In this current work, the magnetic composite microsphere containing glutamine modified chitosan and silica coated Fe3O4 nanoparticles (CS-Gln-MCM) has been successfully prepared and extensively characterized, which is a kind of biodegradable materials. CS-Gln-MCM shows enhanced removal efficiency for both acid green 25 (AG25), an amphoteric dye, and mercury ions (Hg(2+)) from water in the respective while measured pH range compared with chitosan magnetic composite microsphere (CS-MCM) without modification. It is due to the fact that the grafted amino acid provides a variety of additional adsorption active sites and diverse adsorption mechanisms are involved. In AG25 and Hg(2+) aqueous mixture, the modified adsorbents bear preferential adsorption for AG25 over Hg(2+) in strong acidic solutions ascribed to multiple interactions between AG25 and CS-Gln-MCM, such as hydrogen bonding and electrostatic interactions. While, in weak acidic conditions, an efficient simultaneous removal is observed for different adsorption effects involved in aforementioned two pollutants. Besides, CS-Gln-MCM illuminates not only short equilibrium time for adsorption of each pollutant less than 20.0 min but also rapid magnetic separation from water and efficient regeneration after saturated adsorption. Therefore, CS-Gln-MCM bears great application potentials in water treatment. PMID:26618263

  3. Simultaneous removal of acid green 25 and mercury ions from aqueous solutions using glutamine modified chitosan magnetic composite microspheres.

    PubMed

    Tao, Xue; Li, Kun; Yan, Han; Yang, Hu; Li, Aimin

    2016-02-01

    In this current work, the magnetic composite microsphere containing glutamine modified chitosan and silica coated Fe3O4 nanoparticles (CS-Gln-MCM) has been successfully prepared and extensively characterized, which is a kind of biodegradable materials. CS-Gln-MCM shows enhanced removal efficiency for both acid green 25 (AG25), an amphoteric dye, and mercury ions (Hg(2+)) from water in the respective while measured pH range compared with chitosan magnetic composite microsphere (CS-MCM) without modification. It is due to the fact that the grafted amino acid provides a variety of additional adsorption active sites and diverse adsorption mechanisms are involved. In AG25 and Hg(2+) aqueous mixture, the modified adsorbents bear preferential adsorption for AG25 over Hg(2+) in strong acidic solutions ascribed to multiple interactions between AG25 and CS-Gln-MCM, such as hydrogen bonding and electrostatic interactions. While, in weak acidic conditions, an efficient simultaneous removal is observed for different adsorption effects involved in aforementioned two pollutants. Besides, CS-Gln-MCM illuminates not only short equilibrium time for adsorption of each pollutant less than 20.0 min but also rapid magnetic separation from water and efficient regeneration after saturated adsorption. Therefore, CS-Gln-MCM bears great application potentials in water treatment.

  4. p-Aminophenylacetic acid-mediated synthesis of monodispersed titanium oxide hybrid microspheres in ethanol solution.

    PubMed

    Zhang, Hongye; Xie, Yun; Liu, Zhimin; Tao, Ranting; Sun, Zhenyu; Ding, Kunlun; An, Guimin

    2009-10-15

    Monodispersed TiO2 hybrid microspheres were prepared via the hydrolysis of titanium isopropoxide (TTIP) in ethanol solution containing p-aminophenylacetic acid (APA). The effects of the APA:TTIP molar ratio, water content, reaction time and reaction temperature on the morphology of the resultant spheres were investigated. The products were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. It was demonstrated that the diameters of the resultant TiO2 spheres could be tuned in the range of 380-800 nm by changing the APA:TTIP molar ratio (1:3 to 3:1) and water content (1-3 v/v%) in the reaction medium, and that increasing the APA:TTIP molar ratio led to larger TiO2 hybrid spheres while increasing the water content decreased their size. The loading content of APA in the hybrid spheres could reach 20 wt.% as they were prepared with the APA:TTIP ratio of 3:1. The possible formation mechanism of the hybrid spheres was also investigated. It was found that APA slowed down the hydrolysis rate of the titanium precursor so that resulted in the formation of the TiO2 spheres. In addition, the APA present in TiO2 spheres acted as a reducing agent to in situ convert HAuCl4 into metallic Au on the surface of the TiO2 spheres. The catalytic activity of the resultant Au/APA-TiO2 composite was examined using transfer hydrogenation of phenylacetone with 2-propanol, and it was indicated that the catalyst displayed high efficiency for this reaction. PMID:19616218

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

    PubMed

    Mumper, R J; Jay, M

    1992-01-01

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

  6. Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

    PubMed

    Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

    2010-06-01

    Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications. PMID:19777575

  7. Preparation and evaluation of MRI detectable poly (acrylic acid) microspheres loaded with superparamagnetic iron oxide nanoparticles for transcatheter arterial embolization.

    PubMed

    Wang, Huan; Qin, Xiao-Ya; Li, Zi-Yuan; Guo, Li-Ying; Zheng, Zhuo-Zhao; Liu, Li-Si; Fan, Tian-Yuan

    2016-09-25

    To monitor the spatial distribution of embolic particles inside the target tissues during and after embolization, blank poly (acrylic acid) microspheres (PMs) were initially prepared by inverse suspension polymerization method and then loaded with superparamagnetic iron oxide (SPIO) nanoparticles by in situ precipitation method to obtain magnetic resonance imaging (MRI) detectable SPIO-loaded poly (acrylic acid) microspheres (SPMs). The loading of SPIO nanoparticles in SPMs was confirmed by vibrating sample magnetometer, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and infrared spectrum, respectively. The results showed that SPMs exhibited excellent superparamagnetism and the SPIO embedded in SPMs were proved to be inverse spinel magnetite. The content of SPIO loaded in wet SPMs of subgroups of 100-300, 300-500, 500-700 and 700-900μm was measured to be 11.84±0.07, 10.20±0.05, 9.98±0.00 and 8.79±0.01mg/ml, corresponding to the weight percentage in freeze-dried SPMs to be 18.07±0.28%, 18.54±0.13%, 18.66±0.01% and 18.50±0.07%, respectively. The SPMs were spherical in shape, had smooth surface, and were within the size range of clinical demands for embolization. The compression tests indicated that SPMs were more rigid than PMs and commercially used Embospheres (P<0.01). The MRI detectability of SPMs was evaluated with the SPMs embedded in gel phantom in vitro and injected subcutaneously into the back of mice in vivo. Both the results demonstrated that the SPMs could provide distinct negative contrast enhancement and be sensitively detected by T2-weighted MR imaging. All the results show that SPMs are potential MRI detectable embolic microspheres for the future embolotherapy. PMID:27426106

  8. Sustained release of calcium hydroxide from poly(DL-lactide-co-glycolide) acid microspheres for apexification.

    PubMed

    Cerda-Cristerna, Bernardino Isaac; Breceda-Leija, Alejandro; Méndez-González, Verónica; Chavarría-Bolaños, Daniel; Flores-Reyes, Héctor; Garrocho-Rangel, Arturo; Komabayashi, Takashi; Wadajkar, Aniket S; Pozos-Guillén, Amaury J

    2016-09-01

    Calcium hydroxide (CH) loaded poly(DL-lactide-co-glycolide) acid (PLGA) microspheres (MS) might be used for apexification requiring a sustained release of Ca(2+). The aim of this study was to formulate and characterize CH-PLGA-MS. The CH-loaded MS were prepared by either oil-in-water (O/W) or water-in-oil/in-water (W/O/W) emulsion solvent evaporation technique. MS produced by the O/W technique exhibited a larger diameter (18.63 ± 7.23 μm) than the MS produced by the W/O/W technique (15.25 ± 7.37 μm) (Mann-Whitney U test P < 0.001). The CH encapsulation efficiency (E e) and Ca(2+) release were calculated from data obtained by absorption techniques. Ca(2+) release profile was evaluated for 30 days. To know the E e, the CH-loaded MS were dissolved in 1 M NaOH to release all its content and a Ca(2+) colorimetric marker was added to this solution. The reagent marked the Ca(2+) in blue color, which was then measured by a UV-Vis system (650 nm). The percentage of E e was calculated on the basis of the theoretical loading. The E e of the O/W-produced MS was higher (24 %) than the corresponding percentage of the W/O/W-produced MS (11 %). O/W- and W/O/W-produced MS released slower and lower Ca(2+) than a control CH paste with polyethylene glycol 400 (Kruskal-Wallis test). O/W-produced MS released higher Ca(2+) than W/O/W-produced MS (statistically significant differences; P < 0.05). In conclusion, the CH-PLGA-MS were successfully formulated; the technique of formulation influenced the size, encapsulation efficiency and release profile. The MS were better sustained release system than the CH paste.

  9. Highly selective enrichment of baicalin in rat plasma by boronic acid-functionalized core-shell magnetic microspheres: Validation and application to a pharmacokinetic study.

    PubMed

    Huang, Taomin; Xiong, Ya; Chen, Nianzu; Wang, Donglei; Lai, Yonghua; Deng, Chunhui

    2016-01-15

    To the best of our knowledge, this study is the first to successfully apply a novel, highly selective enrichment technique based on boronic acid-functionalized core-shell magnetic microspheres (BA-Fe3O4@SiO2-Au@mSiO2) with a large surface area and uniform pore size, to determine the baicalin concentration in rat plasma by HPLC. By taking advantage of the special interaction between boronic acid and baicalin under alkaline conditions, as well as the microspheres' size exclusion ability, baicalin was selectively extracted from protein-rich biosamples, such as plasma, without any other pretreatment procedure except for a 10-min vortexing step. BA-Fe3O4@SiO2-Au@mSiO2 microsphere-adsorbed baicalin was straightforwardly and rapidly isolated from the matrix using a magnet. Baicalin was subsequently eluted from the microspheres under acidic conditions for 2min for further HPLC analysis. The extraction conditions, such as the amount of microspheres added, adsorption time, adsorption pH, and elution time and pH, were also determined. Furthermore, method validation, including the linear range, detection limit, precision, accuracy, and recovery, were determined. This newly developed method based on BA-Fe3O4@SiO2-Au@mSiO2 microspheres is a simple, accurate, selective, and green analytical preparatory technique for analyzing baicalin in rat plasma. This study will be further novel research on the analysis of complex plasma samples and the pharmacokinetics of drugs similar to baicalin.

  10. Protective effect of recombinant staphylococcal enterotoxin A entrapped in polylactic-co-glycolic acid microspheres against Staphylococcus aureus infection.

    PubMed

    Chen, Liben; Li, Shuang; Wang, Zhengfang; Chang, Ruilong; Su, Jingliang; Han, Bo

    2012-03-19

    Staphylococcus aureus is an important cause of nosocomial and community-acquired infections in humans and animals, as well as the cause of mastitis in dairy cattle. Vaccines aimed at preventing S. aureus infection in bovine mastitis have been studied for many years, but have so far been unsuccessful due to the complexity of the bacteria, and the lack of suitable vaccine delivery vehicles. The current study developed an Escherichia coli protein expression system that produced a recombinant staphylococcal enterotoxin A (rSEA) encapsulated into biodegradable microparticles generated by polylactic-co-glycolic acid (PLGA) dissolved in methylene chloride and stabilized with polyvinyl acetate. Antigen loading and surface properties of the microparticles were investigated to optimize particle preparation protocols. The prepared PLGA-rSEA microspheres had a diameter of approximately 5 μm with a smooth and regular surface. The immunogenicity of the PLGA-rSEA vaccine was assessed using mice as an animal model and showed that the vaccine induced a strong humoral immune response and increased the percent survival of challenged mice and bacterial clearance. Histological analysis showed moderate impairment caused by the pathogen upon challenge afforded by immunization with PLGA-rSEA microspheres. Antibody titer in the sera of mice immunized with PLGA-rSEA microparticles was higher than in vaccinated mice with rSEA. In conclusion, the PLGA-rSEA microparticle vaccine developed here could potentially be used as a vaccine against enterotoxigenic S. aureus.

  11. Neutron activation of holmium poly(L-lactic acid) microspheres for hepatic arterial radio-embolization: a validation study.

    PubMed

    Vente, M A D; Nijsen, J F W; de Roos, R; van Steenbergen, M J; Kaaijk, C N J; Koster-Ammerlaan, M J J; de Leege, P F A; Hennink, W E; van Het Schip, A D; Krijger, G C

    2009-08-01

    Poly(L-lactic acid) microspheres loaded with holmium-166 acetylacetonate (166Ho-PLLA-MS) are a novel microdevice for intra-arterial radio-embolization in patients with unresectable liver malignancies. The neutron activation in a nuclear reactor, in particular the gamma heating, damages the 166Ho-PLLA-MS. The degree of damage is dependent on the irradiation characteristics and irradiation time in a particular reactor facility. The aim of this study was to standardize and objectively validate the activation procedure in a particular reactor. The methods included light- and scanning electron microscopy (SEM), particle size analysis, differential scanning calorimetry, viscometry, thermal neutron flux measurements and energy deposition calculations. Seven hours-neutron irradiation results in sufficient specific activity of the 166Ho-PLLA-MS while structural integrity is preserved. Neutron flux measurements and energy deposition calculations are required in the screening of other nuclear reactors. For the evaluation of microsphere quality, light microscopy, SEM and particle size analysis are appropriate techniques.

  12. Preparation and characterization of polylactic acid microspheres containing water-soluble dyes using a novel w/o/w emulsion solvent evaporation method.

    PubMed

    Uchida, T; Yoshida, K; Goto, S

    1996-01-01

    Polylactic acid (PLA) microspheres containing soluble dyes as water-soluble model compounds were prepared using the water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. Addition of electrolytes such as NaCl or CaCl2 into the external aqueous phase significantly improved brilliant blue (BB) entrapment efficiency compared to the case of no additives. NaCl was the most effective for obtaining high entrapment efficiency (80-90% of theoretical BB content). The average diameter of the obtained microspheres was in the region of 10-20 microns in all cases. PLA microspheres containing 5 and 10% (w/w) BB exhibited the so-called burst release. The release rate decreased with decrease in the internal aqueous droplet volume in the preparation process. In particular, with PLA microspheres containing 5% (w/w) BB, those prepared with the smallest internal droplet volume (63 microliter), the initial burst release was reduced significantly, and 50% (w/w) of the loaded BB remained in the microspheres for 7 days. PMID:8999126

  13. Folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell composite particles: synthesis and application in drug release.

    PubMed

    Yang, Dandan; Wei, Kaiwei; Liu, Qi; Yang, Yong; Guo, Xue; Rong, Hongren; Cheng, Mei-Ling; Wang, Guoxiu

    2013-07-01

    A drug delivery system was designed by deliberately combining the useful functions into one entity, which was composed of magnetic ZnFe2O4 hollow microsphere as the core, and mesoporous silica with folic acid molecules as the outer shell. Amine groups coated magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NH2) composite particles were first synthesized by a one-pot direct co-condensation method. Subsequently a novel kind of folic acid-functionalized magnetic ZnFe2O4 hollow microsphere core/mesoporous silica shell (MZHM-MSS-NHFA) composite particles were synthesized by conjugating folic acid as targeted molecule to MZHM-MSS-NH2. Ibuprofen, a well-known antiphlogistic drug, was used as a model drug to assess the loading and releasing behavior of the composite microspheres. The results show that the MZHM-MSS-NHFA system has the higher capacity of drug storage and good sustained drug-release property.

  14. Application of Carbon-Microsphere-Modified Electrodes for Electrochemistry of Hemoglobin and Electrocatalytic Sensing of Trichloroacetic Acid

    PubMed Central

    Wang, Wen-Cheng; Yan, Li-Jun; Shi, Fan; Niu, Xue-Liang; Huang, Guo-Lei; Zheng, Cai-Juan; Sun, Wei

    2015-01-01

    By using the hydrothermal method, carbon microspheres (CMS) were fabricated and used for electrode modification. The characteristics of CMS were investigated using various techniques. The biocompatible sensing platform was built by immobilizing hemoglobin (Hb) on the micrometer-sized CMS-modified electrode with a layer of chitosan membrane. On the cyclic voltammogram, a couple of quasi-reversible cathodic and anodic peaks appeared, showing that direct electrochemistry of Hb with the working electrode was achieved. The catalytic reduction peak currents of the bioelectrode to trichloroacetic acid was established in the linear range of 2.0~70.0 mmol·L−1 accompanied by a detection limit of 0.30 mmol·L−1 (3σ). The modified electrode displayed favorable sensitivity, good reproducibility and stability, which suggests that CMS is promising for fabricating third-generation bioelectrochemical sensors. PMID:26703621

  15. Application of Carbon-Microsphere-Modified Electrodes for Electrochemistry of Hemoglobin and Electrocatalytic Sensing of Trichloroacetic Acid.

    PubMed

    Wang, Wen-Cheng; Yan, Li-Jun; Shi, Fan; Niu, Xue-Liang; Huang, Guo-Lei; Zheng, Cai-Juan; Sun, Wei

    2015-01-01

    By using the hydrothermal method, carbon microspheres (CMS) were fabricated and used for electrode modification. The characteristics of CMS were investigated using various techniques. The biocompatible sensing platform was built by immobilizing hemoglobin (Hb) on the micrometer-sized CMS-modified electrode with a layer of chitosan membrane. On the cyclic voltammogram, a couple of quasi-reversible cathodic and anodic peaks appeared, showing that direct electrochemistry of Hb with the working electrode was achieved. The catalytic reduction peak currents of the bioelectrode to trichloroacetic acid was established in the linear range of 2.0~70.0 mmol·L(-1) accompanied by a detection limit of 0.30 mmol·L(-1) (3σ). The modified electrode displayed favorable sensitivity, good reproducibility and stability, which suggests that CMS is promising for fabricating third-generation bioelectrochemical sensors. PMID:26703621

  16. Application of Carbon-Microsphere-Modified Electrodes for Electrochemistry of Hemoglobin and Electrocatalytic Sensing of Trichloroacetic Acid.

    PubMed

    Wang, Wen-Cheng; Yan, Li-Jun; Shi, Fan; Niu, Xue-Liang; Huang, Guo-Lei; Zheng, Cai-Juan; Sun, Wei

    2015-12-23

    By using the hydrothermal method, carbon microspheres (CMS) were fabricated and used for electrode modification. The characteristics of CMS were investigated using various techniques. The biocompatible sensing platform was built by immobilizing hemoglobin (Hb) on the micrometer-sized CMS-modified electrode with a layer of chitosan membrane. On the cyclic voltammogram, a couple of quasi-reversible cathodic and anodic peaks appeared, showing that direct electrochemistry of Hb with the working electrode was achieved. The catalytic reduction peak currents of the bioelectrode to trichloroacetic acid was established in the linear range of 2.0~70.0 mmol·L(-1) accompanied by a detection limit of 0.30 mmol·L(-1) (3σ). The modified electrode displayed favorable sensitivity, good reproducibility and stability, which suggests that CMS is promising for fabricating third-generation bioelectrochemical sensors.

  17. Release and pharmacokinetics of near-infrared labeled albumin from monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) microspheres after subcapsular renal injection.

    PubMed

    Kazazi-Hyseni, F; van Vuuren, S H; van der Giezen, D M; Pieters, E H; Ramazani, F; Rodriguez, S; Veldhuis, G J; Goldschmeding, R; van Nostrum, C F; Hennink, W E; Kok, R J

    2015-08-01

    Subcapsular renal injection is a novel administration method for local delivery of therapeutics for the treatment of kidney related diseases. The aim of this study was to investigate the feasibility of polymeric microspheres for sustained release of protein therapeutics in the kidney and study the subsequent redistribution of the released protein. For this purpose, monodisperse poly(d,l-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres (40 μm in diameter) loaded with near-infrared dye-labeled bovine serum albumin (NIR-BSA) were prepared by a membrane emulsification method. Rats were injected with either free NIR-BSA or with NIR-BSA loaded microspheres (NIR-BSA-ms) and the pharmacokinetics of the released NIR-BSA was studied for 3 weeks by ex vivo imaging of organs and blood. Quantitative release data were obtained from kidney homogenates and possible metabolism of the protein was investigated by SDS-PAGE analysis of the samples. The ex vivo images showed a rapid decrease of the NIR signal within 24h in kidneys injected with free NIR-BSA, while, importantly, the signal of the labeled protein was still visible at day 21 in kidneys injected with NIR-BSA-ms. SDS-PAGE analysis of the kidney homogenates showed that intact NIR-BSA was released from the microspheres. The locally released NIR-BSA drained to the systemic circulation and subsequently accumulated in the liver, where it was degraded and excreted renally. The in vivo release of NIR-BSA was calculated after extracting the protein from the remaining microspheres in kidney homogenates. The in vivo release rate was faster (89 ± 4% of the loading in 2 weeks) compared to the in vitro release of NIR-BSA (38 ± 1% in 2 weeks). In conclusion, PLHMGA microspheres injected under the kidney capsule provide a local depot from which a formulated protein is released over a prolonged time-period.

  18. IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1β-mediated degradation of nucleus pulposus in vitro

    PubMed Central

    2012-01-01

    Introduction Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1β) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model. Methods IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days. NP agarose constructs were cultured to functional maturity and treated with combinations of IL-1β and media conditioned with IL-1ra released from microspheres at intervals for up to 20 days. Construct mechanical properties, glycosaminoglycan content, nitrite production and mRNA expression of catabolic mediators were compared to properties for untreated constructs using unpaired Student's t-tests. Results IL-1ra release kinetics were characterized by an initial burst release reducing to a linear release over the first 10 days. IL-1ra released from microspheres attenuated the degradative effects of IL-1β as defined by mechanical properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA expression of inflammatory mediators for 7 days, and continued to limit functional degradation for up to 20 days. Conclusions In this study, we successfully demonstrated that IL-1ra microspheres can attenuate the degradative effects of IL-1β on the NP for extended periods. This therapeutic strategy may be appropriate for treating early-stage, cytokine-mediated disc degeneration. Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation. PMID:22863285

  19. Synthesis of lithium iron phosphate/carbon microspheres by using polyacrylic acid coated iron phosphate nanoparticles derived from iron(III) acrylate.

    PubMed

    Xu, Dongwei; He, Yan-Bing; Chu, Xiaodong; Ding, Zhaojun; Li, Baohua; He, Jianfu; Du, Hongda; Qin, Xianying; Kang, Feiyu

    2015-03-01

    Lithium iron phosphate/carbon (LiFePO4 /C) microspheres with high rate and cycling performance are synthesized from iron phosphate/polyacrylic acid (FePO4 /PAA) nanoparticles. Iron(III) acrylate is used as a precursor for both the iron and carbon sources. FePO4 nanoparticles are first produced by a coprecipitation reaction. The byproduct, acrylic acid ions, is polymerized in situ to form a uniform PAA layer on the surface of the FePO4 nanoparticles. The as-prepared LiFePO4 /C microspheres are composed of primary nanoparticles with sizes of 40-50 nm. The nanoparticles are fully coated with a thin, uniform carbon layer derived from the decomposition of the PAA layer. The uniform carbon-coating layer cooperates with interstitial and boundary carbon derived from sucrose successfully to construct an excellent interconnecting conductive network in the microspheres. As a result of the unique structure, the as-prepared LiFePO4 /C microspheres display both high electronic and ionic conductivities, which contribute to their high rate performance (162.9 mAh g(-1) at 0.1C and 126.1 mAh g(-1) at 5C) and excellent cycling stability (97.1% of capacity retention after 500 cycles at 5C/5C). PMID:25469674

  20. Synthesis of lithium iron phosphate/carbon microspheres by using polyacrylic acid coated iron phosphate nanoparticles derived from iron(III) acrylate.

    PubMed

    Xu, Dongwei; He, Yan-Bing; Chu, Xiaodong; Ding, Zhaojun; Li, Baohua; He, Jianfu; Du, Hongda; Qin, Xianying; Kang, Feiyu

    2015-03-01

    Lithium iron phosphate/carbon (LiFePO4 /C) microspheres with high rate and cycling performance are synthesized from iron phosphate/polyacrylic acid (FePO4 /PAA) nanoparticles. Iron(III) acrylate is used as a precursor for both the iron and carbon sources. FePO4 nanoparticles are first produced by a coprecipitation reaction. The byproduct, acrylic acid ions, is polymerized in situ to form a uniform PAA layer on the surface of the FePO4 nanoparticles. The as-prepared LiFePO4 /C microspheres are composed of primary nanoparticles with sizes of 40-50 nm. The nanoparticles are fully coated with a thin, uniform carbon layer derived from the decomposition of the PAA layer. The uniform carbon-coating layer cooperates with interstitial and boundary carbon derived from sucrose successfully to construct an excellent interconnecting conductive network in the microspheres. As a result of the unique structure, the as-prepared LiFePO4 /C microspheres display both high electronic and ionic conductivities, which contribute to their high rate performance (162.9 mAh g(-1) at 0.1C and 126.1 mAh g(-1) at 5C) and excellent cycling stability (97.1% of capacity retention after 500 cycles at 5C/5C).

  1. New platform for controlled and sustained delivery of the EGF receptor tyrosine kinase inhibitor AG1478 using poly(lactic-co-glycolic acid) microspheres

    PubMed Central

    Robinson, Rebecca; Bertram, James P.; Reiter, Jill L.; Lavik, Erin B.

    2015-01-01

    Inhibition of the epidermal growth factor receptor (EGFR) has been shown to reduce tumor growth and metastases and promote axon regeneration in the central nervous system. Current strategies for inhibiting EGFR include the administration of reversible or irreversible small-molecule tyrosine kinase inhibitors (TKIs). However, to be effective in vivo constant and sustained delivery is required. This study explored the feasibility of encapsulating the tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) in poly(lactic-co-glycolic acid) (PLGA) microspheres to achieve sustained delivery of the TKI. We characterized microspheres prepared using three different emulsion methods: solid-in-oil-in-water, oil-in-water, and oil-in-water with co-solvent. Addition of a co-solvent increased the loading and release of AG1478, and significantly (P<0.001) decreased the size of the microspheres which facilitates administration of the spheres. On average, sustained delivery of AG1478 from microspheres was achieved for six months. However, the addition of a co-solvent prolonged release for over nine months (266 days). In addition, AG1478 retained its bioactivity upon delivery, and inhibited EGFR in both immortalized rat fibroblasts and in EGFR-amplified human carcinoma cells. These results demonstrate that AG1478 can be encapsulated in PLGA and retain bioactivity; thereby providing a new platform for controlled administration of EGFR TKIs. PMID:20055747

  2. Monodisperse aqueous microspheres encapsulating high concentration of l-ascorbic acid: insights of preparation and stability evaluation from straight-through microchannel emulsification.

    PubMed

    Khalid, Nauman; Kobayashi, Isao; Neves, Marcos A; Uemura, Kunihiko; Nakajima, Mitsutoshi; Nabetani, Hiroshi

    2015-01-01

    Stabilization of l-ascorbic acid (l-AA) is a challenging task for food and pharmaceutical industries. The study was conducted to prepare monodisperse aqueous microspheres containing enhanced concentrations of l-AA by using microchannel emulsification (MCE). The asymmetric straight-through microchannel (MC) array used here constitutes 11 × 104 μm microslots connected to a 10 μm circular microholes. 5-30% (w/w) l-AA was added to a Milli-Q water solution containing 2% (w/w) sodium alginate and 1% (w/w) magnesium sulfate, while the continuous phase constitutes 5% (w/w) tetraglycerol condensed ricinoleate in water-saturated decane. Monodisperse aqueous microspheres with average diameters (dav) of 18.7-20.7 μm and coefficients of variation (CVs) below 6% were successfully prepared via MCE regardless of the l-AA concentrations applied. The collected microspheres were physically stable in terms of their dav and CV for >10 days of storage at 40°C. The aqueous microspheres exhibited l-AA encapsulation efficiency exceeding 70% during the storage.

  3. Polyacrylic acid brushes grafted from P(St-AA)/Fe3O4 composite microspheres via ARGET-ATRP in aqueous solution for protein immobilization.

    PubMed

    Xie, Liqin; Lan, Fang; Li, Wenliao; Liu, Ziyao; Ma, Shaohua; Yang, Qi; Wu, Yao; Gu, Zhongwei

    2014-11-01

    Recently, the atom transfer radical polymerization (ATRP) of acrylic monomers in many reaction systems has been successfully accomplished. However, its application in aqueous solution is still a challenging task. In this work, polyacrylic acid (PAA) brushes with tunable length were directly grafted from P(St-AA)/Fe3O4 composite microspheres in aqueous solution via an improved method, activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP). This reaction was carried out in environment-friendly solvent. As well, this method overcame the sensitivity of the catalyst. Due to the strong coordination interaction of carboxyl groups, PAA brushes were employed for immobilizing gold nanoparticles, which were prepared via the in situ reduction of chloroauric acid. The PAA brushes modified magnetic composite microspheres decorating with gold nanoparticles were efficient for specific immobilization and separation of bovine serum albumin (BSA) from aqueous solution under the external magnetic field.

  4. Preparation of ellagic acid molecularly imprinted polymeric microspheres based on distillation-precipitation polymerization for the efficient purification of a crude extract.

    PubMed

    Zhang, Hua; Zhao, Shangge; Zhang, Lu; Han, Bo; Yao, Xincheng; Chen, Wen; Hu, Yanli

    2016-08-01

    Molecularly imprinted polymeric microspheres with a high recognition ability toward the template molecule, ellagic acid, were synthesized based on distillation-precipitation polymerization. The as-obtained polymers were characterized by scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. Static, dynamic, and selective binding tests were adopted to study the binding properties and the molecular recognition ability of the prepared polymers for ellagic acid. The results indicated that the maximum static adsorption capacity of the prepared polymers toward ellagic acid was 37.07 mg/g and the adsorption equilibrium time was about 100 min when the concentration of ellagic acid was 40 mg/mL. Molecularly imprinted polymeric microspheres were also highly selective toward ellagic acid compared with its analogue quercetin. It was found that the content of ellagic acid in the pomegranate peel extract was enhanced from 23 to 86% after such molecularly imprinted solid-phase extraction process. This work provides an efficient way for effective separation and enrichment of ellagic acid from complex matrix, which is especially valuable in industrial production. PMID:27311588

  5. Preparation of ellagic acid molecularly imprinted polymeric microspheres based on distillation-precipitation polymerization for the efficient purification of a crude extract.

    PubMed

    Zhang, Hua; Zhao, Shangge; Zhang, Lu; Han, Bo; Yao, Xincheng; Chen, Wen; Hu, Yanli

    2016-08-01

    Molecularly imprinted polymeric microspheres with a high recognition ability toward the template molecule, ellagic acid, were synthesized based on distillation-precipitation polymerization. The as-obtained polymers were characterized by scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. Static, dynamic, and selective binding tests were adopted to study the binding properties and the molecular recognition ability of the prepared polymers for ellagic acid. The results indicated that the maximum static adsorption capacity of the prepared polymers toward ellagic acid was 37.07 mg/g and the adsorption equilibrium time was about 100 min when the concentration of ellagic acid was 40 mg/mL. Molecularly imprinted polymeric microspheres were also highly selective toward ellagic acid compared with its analogue quercetin. It was found that the content of ellagic acid in the pomegranate peel extract was enhanced from 23 to 86% after such molecularly imprinted solid-phase extraction process. This work provides an efficient way for effective separation and enrichment of ellagic acid from complex matrix, which is especially valuable in industrial production.

  6. A mesoporous silicon/poly-(DL-lactic-co-glycolic) acid microsphere for long time anti-tuberculosis drug delivery.

    PubMed

    Xu, Weikang; Wei, Xinmiao; Wei, Kun; Cao, Xiaodong; Zhong, Shizhen

    2014-12-10

    In this study, drug delivery systems for controlling release of hydrophobic anti-tuberculosis (TB) drug-rifampicin (RIF) or hydrophilic anti-TB drug-isoniazid (INH) from mesoporous silica (MS) were fabricated. The drug was first filled into the mesopores of MS particles, and then the drug-laden MS constructs were incorporated into the bulk of poly-(DL-lactic-co-glycolic) acid (PLGA) microspheres. In comparison with mono-component construct (drug-laden MS and drug-laden PLGA), this multi-component system significantly improved the release time of RIF and INH. For drug-laden MS, about 100% INH was released after 15 h, and about 70% RIF was released after 50 h. For drug-laden PLGA, about 100% INH and RIF were released after 30 and 40 days, respectively. After 60 days, the total RIF and INH release from MS/PLGA had only reached around only 48% and 57%, respectively. This MS/PLGA system could significantly prolong RIF or INH release compared to MS and PLGA. CCK-8 assay demonstrated that this MS/PLGA system had no cytotoxicity. And there has not been study of documenting the controlled release of anti-TB drugs such as RIF or INH from MS/PLGA. Considering the long time release of RIF and INH from MS/PLGA, a new door to bone TB would be opened.

  7. Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan.

    PubMed

    Li, Jingfeng; Jin, Lin; Wang, Mingbo; Zhu, Shaobo; Xu, Shuyun

    2015-07-08

    The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1 μg of rhBMP2/PLGA/CS composite; group B: 3 mg of P24/PLGA/CS composite; group C: 0.5 μg of rhBMP2 + 1.5 mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5 mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post-operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation.

  8. Repair of rat cranial bone defect by using bone morphogenetic protein-2-related peptide combined with microspheres composed of polylactic acid/polyglycolic acid copolymer and chitosan.

    PubMed

    Li, Jingfeng; Jin, Lin; Wang, Mingbo; Zhu, Shaobo; Xu, Shuyun

    2015-08-01

    The effects of the transplanted bone morphogenetic protein-2 (BMP2) -related peptide P24 and rhBMP2 combined with poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS) microspheres were investigated in promoting the repair of rat cranial bone defect. Forty white rats were selected and equally divided into four groups (group A: 1 μg of rhBMP2/PLGA/CS composite; group B: 3 mg of P24/PLGA/CS composite; group C: 0.5 μg of rhBMP2 + 1.5 mg of P24/PLGA/CS composite; group D: blank PLGA/CS material), and rat cranial bone defect models with a diameter of 5 mm were established. The materials were transplanted to the cranial bone defects. The animals were sacrificed on weeks 6 and 12 post-operation. Radiographic examinations (x-ray imaging and 3D CT scanning) and histological evaluations were performed. The repaired areas of cranial bone defects were measured, and the osteogenetic abilities of various materials were compared. Cranial histology, imaging, and repaired area measurements showed that the osteogenetic effects at two time points (weeks 6 and 12) in group C were better than those in groups A and B. The effects in groups A and B were similar. Group D achieved the worst repair effect of cranial bone defects, where a large number of fibrous connective tissues were observed. The PLGA/CS composite microspheres loaded with rhBMP2 and P24 had optimal concrescence and could mutually increase their osteogenesis capability. rhBMP2 + P24/PLGA/CS composite is a novel material for bone defect repair with stable activity to induce bone formation. PMID:26154695

  9. Preparation and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion/solvent evaporation technique.

    PubMed

    Karal-Yılmaz, Okşan; Serhatlı, Müge; Baysal, Kemal; Baysal, Bahattin M

    2011-01-01

    Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60 µm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5 µg VEGF (V5) and 50 µg VEGF (V50) per 500 mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27 ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.

  10. Formulation and evaluation of poly(lactic-co-glycolic acid) microspheres loaded with an altered collagen type II peptide for the treatment of rheumatoid arthritis.

    PubMed

    He, Jintian; Li, Huiqi; Liu, Chao; Wang, Gaizhen; Ge, Lan; Ma, Shufen; Huang, Lijing; Yan, Shaofeng; Xu, Xiaohong

    2015-01-01

    The aim of this research was to evaluate the potential of water-in-oil-in-water (w/o/w) and solid-in-oil-in-water (s/o/w) emulsification techniques to prepare the altered collagen type II peptide AP268-270 (ACTP)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres to make ACTP more convenient as an rheumatoid arthritis treatment. Microspheres produced by the s/o/w method had higher drug encapsulation efficiency (69.7-79.8%) than those prepared by the w/o/w method (21.8-39.3%). In vitro drug release was influenced by the microencapsulation technique, molecular weight, and composition of the polymer. After intramuscular injection of the optimal formulation to Lewis rats, the concentration of ACTP peptide in serum reached its maximum level on day 3 and then remained nearly stable for approximately 4 weeks. In a collagen-induced arthritis rat model, a single intramuscular injection of ACTP-loaded PLGA microspheres had comparable efficacy to the intravenous injection of ACTP peptide solution once every other day.

  11. Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration.

    PubMed

    Tsaryk, Roman; Gloria, Antonio; Russo, Teresa; Anspach, Laura; De Santis, Roberto; Ghanaati, Shahram; Unger, Ronald E; Ambrosio, Luigi; Kirkpatrick, C James

    2015-07-01

    Intervertebral disc (IVD) degeneration is one of the main causes of low back pain. Current surgical treatments are complex and generally do not fully restore spine mobility. Development of injectable extracellular matrix-based hydrogels offers an opportunity for minimally invasive treatment of IVD degeneration. Here we analyze a specific formulation of collagen-low molecular weight hyaluronic acid (LMW HA) semi-interpenetrating network (semi-IPN) loaded with gelatin microspheres as a potential material for tissue engineering of the inner part of the IVD, the nucleus pulposus (NP). The material displayed a gel-like behavior, it was easily injectable as demonstrated by suitable tests and did not induce cytotoxicity or inflammation. Importantly, it supported the growth and chondrogenic differentiation potential of mesenchymal stem cells (MSC) and nasal chondrocytes (NC) in vitro and in vivo. These properties of the hydrogel were successfully combined with TGF-β3 delivery by gelatin microspheres, which promoted the chondrogenic phenotype. Altogether, collagen-LMW HA loaded with gelatin microspheres represents a good candidate material for NP tissue engineering as it combines important rheological, functional and biological features.

  12. Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin augmentation.

    PubMed

    Fan, Min; Liao, Jinfeng; Guo, Gang; Ding, Qiuxia; Yang, Yi; Luo, Feng; Qian, Zhiyong

    2014-04-01

    Soft tissue augmentation using various injectable fillers has gained popularity as more patients seek esthetic improvement through minimally invasive procedures requiring little or no recovery time. The currently available injectable skin fillers can be divided into three categories. With careful assessment, stimulatory fillers are the most ideal fillers. In this study, dexamethasone-loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin augmentation. The biodegradable PECE copolymer can form nano-sized micelles in water, which instantly turns into a non-flowing gel at body temperature due to micellar aggregation. The PECE micelles (making up 90% of composite) served as vehicle for subcutaneous injection were metabolized within 44 days. At the same time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served as stimulus for connective tissue formation. Dexamethasone-loaded PLA microspheres/PECE micelles composite presented great hemocompatibility in vitro. It was demonstrated in the in vive study that the composite was biodegradable, biocompatible, nontoxic and nonmigratory. Histopathological studies indicated that the composite could stimulate collagen regeneration. Furthermore, granuloma, the main complication of the stimulatory fillers, did not appear when the composite was injected into the back of SD rats, because of the dexamethasone controlled release from the composite. All results suggested that dexamethasone-loaded PLA microspheres/PECE micelles composite may be an efficient and promising biomaterial for skin augmentation. PMID:24734511

  13. Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin augmentation.

    PubMed

    Fan, Min; Liao, Jinfeng; Guo, Gang; Ding, Qiuxia; Yang, Yi; Luo, Feng; Qian, Zhiyong

    2014-04-01

    Soft tissue augmentation using various injectable fillers has gained popularity as more patients seek esthetic improvement through minimally invasive procedures requiring little or no recovery time. The currently available injectable skin fillers can be divided into three categories. With careful assessment, stimulatory fillers are the most ideal fillers. In this study, dexamethasone-loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin augmentation. The biodegradable PECE copolymer can form nano-sized micelles in water, which instantly turns into a non-flowing gel at body temperature due to micellar aggregation. The PECE micelles (making up 90% of composite) served as vehicle for subcutaneous injection were metabolized within 44 days. At the same time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served as stimulus for connective tissue formation. Dexamethasone-loaded PLA microspheres/PECE micelles composite presented great hemocompatibility in vitro. It was demonstrated in the in vive study that the composite was biodegradable, biocompatible, nontoxic and nonmigratory. Histopathological studies indicated that the composite could stimulate collagen regeneration. Furthermore, granuloma, the main complication of the stimulatory fillers, did not appear when the composite was injected into the back of SD rats, because of the dexamethasone controlled release from the composite. All results suggested that dexamethasone-loaded PLA microspheres/PECE micelles composite may be an efficient and promising biomaterial for skin augmentation.

  14. Efficient decolorization and deproteinization using uniform polymer microspheres in the succinic acid biorefinery from bio-waste cotton (Gossypium hirsutum L.) stalks.

    PubMed

    Li, Qiang; Lei, Jiandu; Zhang, Rongyue; Li, Juan; Xing, Jianmin; Gao, Fei; Gong, Fangling; Yan, Xiaofeng; Wang, Dan; Su, Zhiguo; Ma, Guanghui

    2013-05-01

    Bio-waste cotton (Gossypium hirsutum L.) stalks were converted into succinic acid by simultaneous saccharification and fermentation (SSF) using Actinobacillus succinogenes 130Z. After 54 h SSF at 40 °C and pH 7.0, the production of succinic acid was 63 g/L, with 1.17 g/L/h productivity and 64% conversion yield. After SSF, a simple method for the decolorization and deproteinization of crude SSF broth was developed through adsorption tests of polystyrene (PSt) microspheres. Under optimized conditions (5% PSt loading (w/v), pH 4.0, 60 °C and adsorption time of 40 min), the ratios of decolorization, deproteinization and succinic acid loss ratios were 96.6, 84.5 and 4.1%, respectively. The method developed will provide a potential approach for large-scale production of succinic acid from the biomass waste. PMID:22985822

  15. Glass microspheres

    SciTech Connect

    Day, D.E.; Ehrhardt, G.J.

    1988-12-06

    This patent describes a glass microsphere having a diameter of about 54 micrometers or less and adapted for radiation therapy of a mammal. The glass consists of essentially an yttrium oxide-aluminosilicate glass composition lying substantially within a quadrilateral region of the ternary composition diagram of the yttria-alumina-silica system, the quadrilateral region being defined by its four corners having the following combination of weight proportions of the components: 20% silica, 10% alumina, 70% yttria; 70% silica, 10% alumina, 20% yttria; 70% silica, 20% alumina, 10% yttria; and 20% silica, 45% alumina, 35% yttria, the glass having a chemical durability such that subsequent to irradiation and administration of the microsphere to the mammal, the mircosphere will not release a significant amount of yttrium-90 into the mammal's system.

  16. Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

    PubMed

    Niu, Xufeng; Liu, Zhongning; Hu, Jiang; Rambhia, Kunal J; Fan, Yubo; Ma, Peter X

    2016-07-01

    To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects. PMID:26987445

  17. Synthesis of caffeic acid molecularly imprinted polymer microspheres and high-performance liquid chromatography evaluation of their sorption properties.

    PubMed

    Valero-Navarro, Angel; Gómez-Romero, María; Fernández-Sánchez, Jorge F; Cormack, Peter A G; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

    2011-10-14

    In the current work, a molecularly imprinted polymer (MIP) has been synthesised and used to enable the extraction of a naturally-occurring antioxidant from complex media. More specifically, we describe the first example of a caffeic acid (CA) MIP which has been synthesised in the form of well-defined polymer microspheres, and its use for the extraction of CA from fruit juice sample. The CA MIP was synthesised by precipitation polymerisation using 4-vinylpyridine as functional monomer, divinylbenzene-80 as crosslinker and acetonitrile:toluene (75/25, v/v) as porogen. The particle sizing and morphological characterisation of the polymers was carried out by means of scanning electron microscopy (narrow particle size distribution; ∼5 and 1.5 μm particle diameters for the MIP and NIP [non-imprinted polymer], respectively) and nitrogen sorption porosimetry (specific surface areas of 340 and 350 m(2)g(-1), and specific pore volumes of 0.17 and 0.19 cm(3)g(-1) for the MIP and NIP, respectively). The polymers were evaluated further by batch rebinding experiments, and from the derived isotherms their binding capacity and binding strength were determined (number of binding sites (N(K))=0.6 and 0.3 mmol g(-1) for the MIP and NIP, respectively, and apparent average adsorption constant (K(N))=10.0 and 1.6L mmol(-1) for the MIP and NIP, respectively). To evaluate the molecular recognition character of the MIP it was packed into a stainless steel column (50 mm × 4.6 mm i.d.) and evaluated as an HPLC-stationary phase. The mobile phase composition, flow rate, and the elution profile were then optimised in order to improve the peak shape without negatively affecting the imprinting factor (IF). Very interesting, promising properties were revealed. The imprinting factor (IF) under the optimised conditions was 11.9. Finally, when the imprinted LC column was used for the selective recognition of CA over eight related compounds, very good selectivity was obtained. This outcome enabled

  18. Microradiographic microsphere manipulator

    DOEpatents

    Singleton, R.M.

    A method and apparatus is disclosed for radiographic characterization of small hollow spherical members (microspheres), constructed of either optically transparent or opaque materials. The apparatus involves a microsphere manipulator which holds a batch of microspheres between two parallel thin plastic films for contact microradiographic characterization or projection microradiography thereof. One plastic film is translated relative to and parallel to the other to roll the microspheres through any desired angle to allow different views of the microspheres.

  19. Microradiographic microsphere manipulator

    DOEpatents

    Singleton, Russell M.

    1980-01-01

    A method and apparatus for radiographic characterization of small hollow spherical members (microspheres), constructed of either optically transparent or opaque materials. The apparatus involves a microsphere manipulator which holds a batch of microspheres between two parallel thin plastic films for contact microradiographic characterization or projection microradiography thereof. One plastic film is translated to relative to and parallel to the other to roll the microspheres through any desired angle to allow different views of the microspheres.

  20. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects.

    PubMed

    He, Shu; Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang; Bi, Long; Liu, Jian

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration.

  1. Evaluations of therapeutic efficacy of intravitreal injected polylactic-glycolic acid microspheres loaded with triamcinolone acetonide on a rabbit model of uveitis.

    PubMed

    Li, Wenchang; He, Bing; Dai, Wenbing; Zhang, Qiang; Liu, Yuling

    2014-06-01

    Conventional treatments of uveitis are not ideal because of the short period of therapeutic efficacy. In the present study, biodegradable polylactic-glycolic acid microspheres loaded with triamcinolone acetonide (TA) were prepared to achieve sustained drug release and their therapeutic efficacy was investigated on a rabbit model of uveitis. TA-loaded microspheres (TA-MS) were prepared by the solvent evaporation method and characterized for encapsulation efficiency, particle size, morphology and in vitro release. The therapeutic efficacy was studied on the rabbit experimental uveitis model based on scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination and histological examination. The TA-MS exhibited smooth and intact surfaces with an average diameter of 50.87 μm. The drug-loading coefficient and encapsulation efficiency were 15.2 ± 0.6 % and 91.24 ± 3.77 %, respectively. The drug release from TA-MS lasted up to 87 days, but only 46 days for TA suspension. The change in surface morphology also showed sustained drug release from TA-MS. TA-MS exhibited improved therapeutic efficacy in lipopolysaccharide -induced uveitis compared to TA suspension, especially in regard to the inhibition of inflammation. The TA-MS had a longer-term therapeutic effect on intraocular inflammation in LPS-induced uveitis in rabbits compared to TA suspension. The results suggested that TA-MS can be developed as a potential sustained-release system for the treatment of uveitis.

  2. Spray-dried chitosan microspheres containing 8-hydroxyquinoline -5 sulphonic acid as a new adsorbent for Cd(II) and Zn(II) ions.

    PubMed

    Vitali, Luciano; Laranjeira, Mauro C M; Gonçalves, Norberto S; Fávere, Valfredo T

    2008-03-01

    In the present study, a new chelating adsorbent was prepared from chitosan microspheres cross-linked with glutaraldehyde by spray drying using 8-hydroxyquinoline -5 sulphonic acid as chelant agent (CTS-SX-CL). Microspheres of the new adsorbent were characterized by Raman spectroscopy, scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX). The effect of pH, contact time and concentration of metallic ions in solution were evaluated on the adsorption behavior of Cd(II) and Zn(II) by CTS-SX-CL. Adsorption was maximum for both Cd(II) and Zn(II) at pH 8.0. Adsorption kinetic curves were obtained and could be fit by the pseudo second-order adsorption model. An analysis of equilibrium adsorption data using the Langmuir isotherm model indicated that the maximum adsorption capacity of CTS-SX-CL was higher than that of CTS-CL for both ions investigated. The adsorption capacity increased 74% for Cd(II).

  3. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects

    PubMed Central

    Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration. PMID:27652269

  4. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects.

    PubMed

    He, Shu; Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang; Bi, Long; Liu, Jian

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration. PMID:27652269

  5. Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-co-glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method.

    PubMed

    Pathak, Shiva; Gupta, Biki; Poudel, Bijay Kumar; Tran, Tuan Hiep; Regmi, Shobha; Pham, Tung Thanh; Thapa, Raj Kumar; Kim, Min-Soo; Yong, Chul Soon; Kim, Jong Oh; Jeong, Jee-Heon

    2016-01-01

    Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug-loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81±0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The in vitro release study showed prolonged release patterns. TAC-PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electrospray method. PMID:26833445

  6. Synergistic Effect of Mesoporous Silica and Hydroxyapatite in Loaded Poly(DL-lactic-co-glycolic acid) Microspheres on the Regeneration of Bone Defects

    PubMed Central

    Lin, Kai-Feng; Fan, Jun-Jun; Hu, Gang; Dong, Xin; Zhao, Yi-Nan; Song, Yue; Guo, Zhong-Shang

    2016-01-01

    A microsphere composite made of poly(DL-lactic-co-glycolic acid) (PLGA), mesoporous silica nanoparticle (MSN), and nanohydroxyapatite (nHA) (PLGA-MSN/nHA) was prepared and evaluated as bone tissue engineering materials. The objective of this study was to investigate the synergistic effect of MSN/nHA on biocompatibility as well as its potential ability for bone formation. First, we found that this PLGA-MSN/nHA composite performed good characteristics on microstructure, mechanical strength, and wettability. By cell culture experiments, the adhesion and proliferation rate of the cells seeded on PLGA-MSN/nHA composite was higher than those of the controls and high levels of osteogenetic factors such as ALP and Runx-2 were detected by reverse transcriptase polymerase chain reaction. Finally, this PLGA-MSN/nHA composite was implanted into the femur bone defect in a rabbit model, and its ability to induce bone regeneration was observed by histological examinations. Twelve weeks after implantation, the bone defects had significantly more formation of mature bone and less residual materials than in the controls. These results demonstrate that this PLGA-MSN/nHA composite, introducing both MSN and nHA into PLGA microspheres, can improve the biocompatibility and osteoinductivity of composite in vitro and in vivo and had potential application in bone regeneration.

  7. Hybrid microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Richard C. K. (Inventor)

    1985-01-01

    Substrates, particularly inert synthetic organic resin beads (10) or sheet (12) such as polystyrene are coated with a covalently bound layer (24) of polyacrolein by irradiation a solution (14) of acrolein or other aldehyde with high intensity radiation. Individual microspheres (22) are formed which attach to the surface to form the aldehyde containing layer (24). The aldehyde groups can be converted to other functional groups by reaction with materials such as hydroxylamine. Adducts of proteins such as antibodies or enzymes can be formed by direct reaction with the surface aldehyde groups.

  8. Chemical composition of plasma treated polyimide microspheres

    NASA Astrophysics Data System (ADS)

    Gawdzik, Barbara; Sobiesiak, Magdalena

    2003-05-01

    Synthetic carbon microspheres for chromatography were obtained from porous copolymer of 4,4'-bis(maleimidodiphenyl)methane (BM) and divinylbenzene (DVB) using arc discharge argon plasma treatment. Chemical structure of the obtained material was determined by elemental analysis, scanning electron microscopy with X-ray detector, acid and base titrations, and atomic absorption spectroscopy. The results suggest that the carbon microspheres contain copper coming from the plasma reactor electrodes. To remove it two complexion agents were used: EDTA and 20% HNO 3. Copper can be removed from the surface using these methods. The other amount was permanently built into internal structure of the microspheres.

  9. Selective delivery of rifampicin incorporated into poly(DL-lactic-co-glycolic) acid microspheres after phagocytotic uptake by alveolar macrophages, and the killing effect against intracellular Mycobacterium bovis Calmette-Guérin.

    PubMed

    Yoshida, Aya; Matumoto, Makoto; Hshizume, Hiroyuki; Oba, Yoshiro; Tomishige, Tatuo; Inagawa, Hiroyuki; Kohchi, Chie; Hino, Mami; Ito, Fuminori; Tomoda, Keishiro; Nakajima, Takehisa; Makino, Kimiko; Terada, Hiroshi; Hori, Hitoshi; Soma, Gen-Ichiro

    2006-08-01

    Macrophages and their phagocytotic abilities play a dominant role for defense against infected organisms. However, Mycobacterium tuberculosis can survive in the phagosomes of macrophages. In this study, the effective delivery of a drug and the killing effect of tubercle bacilli within macrophages were investigated utilizing the phagocytotic uptake of rifampicin (RFP) that had been incorporated into poly(DL-lactic-co-glycolic) acid (PLGA) microspheres. The microspheres were composed of PLGA that had a monomer ratio (lactic acid/glycolic acid) of either 50/50 or 75/25. They had molecular weights from 5000 to 20,000, and diameters of 1.5, 3.5, 6.2 and 8.9 microm. The most significant factor for phagocytotic activity of macrophages was the diameter of the microspheres. By contrast, molecular weight and monomer ratio of PLGA did not influence phagocytosis. The amount of RFP delivered into cells was also investigated. RFP-PLGA microspheres composed of PLGA with a molecular weight of 20,000 and monomer ratio of 75/25 showed the highest amount of delivery (4 microg/1 x 10(6) cells). Fourteen days after infection, the survival rate of treated intracellular bacilli was 1% when compared with untreated cells. There was almost no killing effect of free RFP (4 or 15 microg/ml) on intracellular bacilli. In vivo efficacy of RFP-PLGA was also examined in rats infected with M. tuberculosis Kurono. Intratracheal administration of RFP-PLGA microspheres was shown to be superior to free RFP for killing of intracellular bacilli and preventing granuloma formation in some lobes. These results suggest that phagocytotic activity could be part of a new drug delivery system that selectively targeted macrophages.

  10. The effect of AZD2171- or sTRAIL/Apo2L-loaded polylactic-co-glycolic acid microspheres on a subcutaneous glioblastoma model.

    PubMed

    Shivinsky, Anna; Bronshtein, Tomer; Haber, Tom; Machluf, Marcelle

    2015-08-01

    Studies with AZD2171-a new anti-angiogenic inhibitor of tyrosine kinases associated with VEGF signaling-have shown great promise for treating glioblastoma. Unfortunately, AZD2171 success is limited by low permeability through the blood-brain barrier. Due to AZD2171's short half-life and high toxicity, its local administration will require multiple intracranial procedures, making this approach clinically unfeasible. In this study, we investigated the potential of the highly hydrophobic AZD2171, released from modified polylactic-co-glycolic acid microspheres (PLGA-MS), to treat glioblastoma. To further demonstrate the versatile loading capacity of this system, the same PLGA formulation, which was found optimal for the loading and release of AZD2171, was tested with sTRAIL/Apo2L-a biologic drug that is very different than AZD2171 in its molecular weight, solubility, and charge. AZD2171 released from PLGA-MS was at least effective as the free drug in inhibiting endothelial growth and proliferation (in vitro), and, surprisingly, had a profound cytotoxic effect also towards in vitro cultured glioblastoma cell-lines (U87 and A172). Complete tumor inhibition was achieved following a single treatment with AZD2171-loaded PLGA-MS (6 (mg)/kg) administered locally adjacent to human U87 glioma tumors inoculated subcutaneously in nude mice. This improved effect, compared to other therapeutic approaches involving AZD2171, was shown to affect both tumor vasculature and the glioma cells. sTRAIL-loaded microspheres, administered at very low doses (0.3 (mg)/kg), led to 35 % inhibition of tumor growth in 2 weeks. Collectively, our results provide pre-clinical evidence for the potential of PLGA formulations of AZD2171 and sTRAIL to serve as an effective treatment for glioblastoma.

  11. Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

    PubMed

    Ruiz, J M; Busnel, J P; Benoît, J P

    1990-09-01

    The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes. PMID:2235892

  12. Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

    PubMed

    Ruiz, J M; Busnel, J P; Benoît, J P

    1990-09-01

    The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes.

  13. Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

    PubMed

    Yasunami, Noriyuki; Ayukawa, Yasunori; Furuhashi, Akihiro; Atsuta, Ikiru; Rakhmatia, Yunia Dwi; Moriyama, Yasuko; Masuzaki, Tomohiro; Koyano, Kiyoshi

    2016-02-01

    Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site. PMID:26694986

  14. Quantitative three-dimensional analysis of poly (lactic-co-glycolic acid) microsphere using hard X-ray nano-tomography revealed correlation between structural parameters and drug burst release.

    PubMed

    Huang, Xiaozhou; Li, Na; Wang, Dajiang; Luo, Yuyan; Wu, Ziyu; Guo, Zhefei; Jin, Qixing; Liu, Zhuying; Huang, Yafei; Zhang, Yongming; Wu, Chuanbin

    2015-08-10

    The objective of this study was to investigate the use of transmission hard X-ray nano-computed-tomography (nano-CT) for characterization of the pore structure and drug distribution in poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating bovine serum albumin and to study the correlation between drug distribution and burst release. The PLGA microspheres were fabricated using a double-emulsion method. The results of pore structure analysis accessed with nano-CT were compared with those acquired by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). Surface pore interconnectivity and surface protein interconnectivity were obtained using combined nano-CT and pixel analysis. The correlation between surface protein interconnectivity with the initial burst release across various tested formulations was also analyzed. The size, shape, and distribution of the pores and protein could be clearly observed in the whole microsphere using nano-CT, whereas only the sectional information was observed using SEM or CLSM. Interconnected pores and surface connected pores could be clearly distinguished in nano-CT, which enables the quantitative analysis of surface pore interconnectivity and surface protein interconnectivity. The surface protein interconnectivity in different formulations correlated well with the burst release at 5-10h. Nano-CT provided a nondestructive, high-resolution, and three-dimensional analysis method to characterize the porous microsphere.

  15. Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

    PubMed

    Yasunami, Noriyuki; Ayukawa, Yasunori; Furuhashi, Akihiro; Atsuta, Ikiru; Rakhmatia, Yunia Dwi; Moriyama, Yasuko; Masuzaki, Tomohiro; Koyano, Kiyoshi

    2015-12-23

    Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

  16. microsphere assemblies

    NASA Astrophysics Data System (ADS)

    Peña-Flores, Jesús I.; Palomec-Garfias, Abraham F.; Márquez-Beltrán, César; Sánchez-Mora, Enrique; Gómez-Barojas, Estela; Pérez-Rodríguez, Felipe

    2014-09-01

    The effect of Fe ion concentration on the morphological, structural, and optical properties of TiO2 films supported on silica (SiO2) opals has been studied. TiO2:Fe2O3 films were prepared by the sol-gel method in combination with a vertical dip coating procedure; precursor solutions of Ti and Fe were deposited on a monolayer of SiO2 opals previously deposited on a glass substrate by the same procedure. After the dip coating process has been carried out, the samples were thermally treated to obtain the TiO2:Fe2O3/SiO2 composites at the Fe ion concentrations of 1, 3, and 5 wt%. Scanning electron microscopy (SEM) micrographs show the formation of colloidal silica microspheres of about 50 nm diameter autoensembled in a hexagonal close-packed fashion. Although the X-ray diffractograms show no significant effect of Fe ion concentration on the crystal structure of TiO2, the μ-Raman and reflectance spectra do show that the intensity of a phonon vibration mode and the energy bandgap of TiO2 decrease as the Fe+3 ion concentration increases.

  17. PLGA/alginate composite microspheres for hydrophilic protein delivery.

    PubMed

    Zhai, Peng; Chen, X B; Schreyer, David J

    2015-11-01

    Poly(lactic-co-glycolic acid) (PLGA) microspheres and PLGA/alginate composite microspheres were prepared by a novel double emulsion and solvent evaporation technique and loaded with bovine serum albumin (BSA) or rabbit anti-laminin antibody protein. The addition of alginate and the use of a surfactant during microsphere preparation increased the encapsulation efficiency and reduced the initial burst release of hydrophilic BSA. Confocal laser scanning microcopy (CLSM) of BSA-loaded PLGA/alginate composite microspheres showed that PLGA, alginate, and BSA were distributed throughout the depths of microspheres; no core/shell structure was observed. Scanning electron microscopy revealed that PLGA microspheres erode and degrade more quickly than PLGA/alginate composite microspheres. When loaded with anti-laminin antibody, the function of released antibody was well preserved in both PLGA and PLGA/alginate composite microspheres. The biocompatibility of PLGA and PLGA/alginate microspheres were examined using four types of cultured cell lines, representing different tissue types. Cell survival was variably affected by the inclusion of alginate in composite microspheres, possibly due to the sensitivity of different cell types to excess calcium that may be released from the calcium cross-linked alginate.

  18. An Inorganic Microsphere Composite for the Selective Removal of 137 Cesium from Acidic Nuclear Waste Solutions 2: Bench-Scale Column Experiments, Modeling, and Preliminary Process Design

    SciTech Connect

    Troy J. Tranter; T. A. Vereschagina; V. Utgikar

    2009-03-01

    A new inorganic ion exchange composite for removing radioactive cesium from acidic waste streams has been developed. The new material consists of ammonium molybdophosphate, (NH4)3P(Mo3O10)4?3H2O (AMP), synthesized within hollow aluminosilicate microspheres (AMP-C), which are produced as a by-product from coal combustion. The selective cesium exchange capacity of this inorganic composite was evaluated in bench-scale column tests using simulated sodium bearing waste solution as a surrogate for the acidic tank waste currently stored at the Idaho National Laboratory (INL). Total cesium loading on the columns at saturation agreed very well with equilibrium values predicted from isotherm experiments performed previously. A numerical algorithm for solving the governing partial differential equations (PDE) for cesium uptake was developed using the intraparticle mass transfer coefficient obtained from previous batch kinetic experiments. Solutions to the governing equations were generated to obtain the cesium concentration at the column effluent as a function of throughput volume using the same conditions as those used for the actual column experiments. The numerical solutions of the PDE fit the column break through data quite well for all the experimental conditions in the study. The model should therefore provide a reliable prediction of column performance at larger scales.

  19. Sustained release poly (lactic-co-glycolic acid) microspheres of bone morphogenetic protein 2 plasmid/calcium phosphate to promote in vitro bone formation and in vivo ectopic osteogenesis

    PubMed Central

    Qiao, Chunyan; Zhang, Kai; Sun, Bin; Liu, Jinzhong; Song, Jiyu; Hu, Yue; Yang, Shihui; Sun, Hongchen; Yang, Bai

    2015-01-01

    Bone regeneration often requires continuous stimulation to promote local bone formation. In the present study, calcium phosphate (CaPi) was used to promote transfection of human bone morphogenetic protein 2 (BMP-2) cDNA plasmid, and poly (lactic-co-glycolic acid) (PLGA) was used to prepare microspheres of pBMP-2/CaPi (i.e., PLGA@pBMP-2/CaPi) using W/O/W double emulsion solvent evaporation method. We showed that PLGA@pBMP-2/CaPi microspheres were spherical with smooth surface, and the particle size ranged from 0.5 to 35 μm. Encapsulation efficiency was up to 30~50%. The release of BMP-2 cDNA from microspheres continued more than 30 days and constituted, less than 7.5% of total plasmid amount within the first 24 h. Real-time PCR results showed that co-culturing of PLGA@pBMP-2/CaPi with bone marrow-derived mesenchymal stem cells (BMSCs) increased calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7, and collagen type I (COLL I) in a time-dependent manner. Finally, X-ray analysis demonstrated that in vivo delivery of PLGA@pBMP-2/CaPi microspheres into the tibialis anterior muscles of rats promoted the generation of osteoblasts, bone tissue, and bone structure. The findings suggested that PLGA@pBMP-2/CaPi microspheres can promote ectopic osteogenesis in non-bone tissues, with strong prospects in promoting bone regeneration. PMID:26885257

  20. Coacervate droplets, proteinoid microspheres, and the genetic apparatus

    NASA Technical Reports Server (NTRS)

    Fox, S. W.

    1974-01-01

    Differences between typical coacervate droplets and typical proteinoid microspheres are examined. It is pointed out that coacervate droplets are produced from polymers obtained from contemporary organisms. The microspheres considered are aggregates of proteinoid formed from monomeric amino acids under geologically relevant conditions. Aspects regarding the primordial sequence are discussed along with the origin of the genetic apparatus and the genetic code.

  1. Preparation of chitosan/poly(acrylic acid) magnetic composite microspheres and applications in the removal of copper(II) ions from aqueous solutions.

    PubMed

    Yan, Han; Yang, Lingyun; Yang, Zhen; Yang, Hu; Li, Aimin; Cheng, Rongshi

    2012-08-30

    In this current work, the magnetic composite microspheres (MCM), consisting of Fe(3)O(4) nanoparticles and poly(acrylic acid) (PAA) blended chitosan (CS), were prepared successfully by a simple method, co-precipitation of the compounds in alkaline solution. SEM, FTIR and TG techniques have been applied to investigate the structures of the MCM materials. The vibrating-sample magnetometer (VSM) measurement illustrated a paramagnetic property as well as a fast magnetic response, which indicated the significant separability of the MCM in the aqueous suspensions. Then, the MCM materials were employed as absorbents for removal of copper(II) (Cu(II)) ions from aqueous solutions. The fundamental adsorption behaviors of MCM were studied also. Experimental results revealed that the CS/PAA-MCM had greater adsorption capacity than CS-MCM, and PAA played an important role for the adsorption of Cu(II) ions. Moreover, the adsorption isotherms were all well described by the Langmuir model, while the adsorption kinetics followed the pseudo-second order equation. Furthermore, the adsorbent could be easily regenerated at lower pH and reused almost without any loss of adsorption capacity. On the contrary, the Cu(II) ions loaded CS-MCM and CS/PAA-MCM were stable enough at pH higher than 4.0, and both exhibited efficient phosphate removal with maximal uptakes around 63.0 and 108.0 mg Pg(-1), respectively. PMID:22749139

  2. Membranes for specific adsorption: immobilizing molecularly imprinted polymer microspheres using electrospun nanofibers.

    PubMed

    Büttiker, Roman; Ebert, Jürgen; Hinderling, Christian; Adlhart, Christian

    2011-01-01

    Molecularly imprinted polymer microspheres were immobilized within a polymer nanofiber membrane by electrospinning. Such membranes simplify the handling of functional microspheres and provide specific recognition capabilities for solid-phase extraction and filtration applications. In this study, microspheres were prepared by precipitation polymerization of methacrylic acid and divinylbenzene as a cross-linker with the target molecule (-)-cinchonidine and then, they were electrospun into a non-woven polyacrylonitrile nanofiber membrane. The composite membrane showed specific affinity for (-)-cinchonidine which was attributed to the functional microspheres as confirmed by Raman microscopy. The target molecule capturing capacity of the composite membrane was 5 mg/g or 25 mg/g immobilized functional microsphere. No difference in target affinity was observed between the immobilized microspheres and the free microspheres. These results reveal that electrospun composite membranes are a feasible approach to immobilizing functional microspheres.

  3. Membranes for specific adsorption: immobilizing molecularly imprinted polymer microspheres using electrospun nanofibers.

    PubMed

    Büttiker, Roman; Ebert, Jürgen; Hinderling, Christian; Adlhart, Christian

    2011-01-01

    Molecularly imprinted polymer microspheres were immobilized within a polymer nanofiber membrane by electrospinning. Such membranes simplify the handling of functional microspheres and provide specific recognition capabilities for solid-phase extraction and filtration applications. In this study, microspheres were prepared by precipitation polymerization of methacrylic acid and divinylbenzene as a cross-linker with the target molecule (-)-cinchonidine and then, they were electrospun into a non-woven polyacrylonitrile nanofiber membrane. The composite membrane showed specific affinity for (-)-cinchonidine which was attributed to the functional microspheres as confirmed by Raman microscopy. The target molecule capturing capacity of the composite membrane was 5 mg/g or 25 mg/g immobilized functional microsphere. No difference in target affinity was observed between the immobilized microspheres and the free microspheres. These results reveal that electrospun composite membranes are a feasible approach to immobilizing functional microspheres. PMID:21528654

  4. Doxorubicin-loaded poly(lactic-co-glycolic acid) microspheres prepared using the solid-in-oil-in-water method for the transarterial chemoembolization of a liver tumor.

    PubMed

    Choi, Jin Woo; Park, Ju-Hwan; Baek, Song Yi; Kim, Dae-Duk; Kim, Hyo-Cheol; Cho, Hyun-Jong

    2015-08-01

    Doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres (MSs) were fabricated using the solid-in-oil-in-water (S/O/W) emulsification method for transarterial chemoembolization (TACE) of a liver tumor. DOX-loaded PLGA MSs with a mean diameter of 26 μm and a spherical shape were prepared. The biodegradation of PLGA MSs was observed in serum using a scanning electron microscope (SEM). Drug release from the PLGA MSs was accelerated at an acidic pH (pH 5.5) compared to a normal physiological pH (pH 7.4). According to the results of a pharmacokinetic study in rats, the area under the curve (AUC) value of a drug, which indicates the systemic exposure extent of the drug, of the PLGA MSs group was 29.9% of that of a hepatic arterial injection (HAI) group. The DOX concentration ratio for liver tumors compared to normal livers was significantly higher in the PLGA MSs group than that of the HAI group (p<0.05). After the TACE procedure was performed with DOX-PLGA MSs in a rat hepatoma model, the mean size increment of tumor in DOX-PLGA MSs group was found to be lower than that of the HAI group, and the viable portion of the DOX-PLGA MSs group was less than the other groups (p<0.05). All these findings suggested that the developed DOX-loaded PLGA MSs fabricated with the S/O/W method can be used as a promising drug delivery system in TACE for liver tumors.

  5. Microspheres prepared with different co-polymers of poly(lactic-glycolic acid) (PLGA) or with chitosan cause distinct effects on macrophages.

    PubMed

    Bitencourt, Claudia da Silva; Silva, Letícia Bueno da; Pereira, Priscilla Aparecida Tartari; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-12-01

    Microencapsulation of bioactive molecules for modulating the immune response during infectious or inflammatory events is a promising approach, since microspheres (MS) protect these labile biomolecules against fast degradation, prolong the delivery over longer periods of time and, in many situations, target their delivery to site of action, avoiding toxic side effects. Little is known, however, about the influence of different polymers used to prepare MS on macrophages. This paper aims to address this issue by evaluating in vitro cytotoxicity, phagocytosis profile and cytokines release from alveolar macrophages (J-774.1) treated with MS prepared with chitosan, and four different co-polymers of PLGA [poly (lactic-co-glycolic acid)]. The five MS prepared presented similar diameter and zeta potential each other. Chitosan-MS showed to be cytotoxic to J-774.1 cells, in contrast to PLGA-MS, which were all innocuous to this cell linage. PLGA 5000-MS was more efficiently phagocytized by macrophages compared to the other MS tested. PLGA 5000-MS and 5002-MS induced significant production of TNF-α, while 5000-MS, 5004-MS and 7502-MS decreased spontaneous IL-6 release. Nevertheless, only PLGA 5002-MS induced significant NFkB/SEAP activation. These findings together show that MS prepared with distinct PLGA co-polymers are differently recognized by macrophages, depending on proportion of lactic and glycolic acid in polymeric chain, and on molecular weight of the co-polymer used. Selection of the most adequate polymer to prepare a microparticulate drug delivery system to modulate immunologic system may take into account, therefore, which kind of immunomodulatory response is more adequate for the required treatment.

  6. Surface Wrinkling on Polydimethylsiloxane Microspheres via Wet Surface Chemical Oxidation

    PubMed Central

    Yin, Jian; Han, Xue; Cao, Yanping; Lu, Conghua

    2014-01-01

    Here we introduce a simple low-cost yet robust method to realize spontaneously wrinkled morphologies on spherical surfaces. It is based on surface chemical oxidation of aqueous-phase-synthesized polydimethylsiloxane (PDMS) microspheres in the mixed H2SO4/HNO3/H2O solution. Consequently, curvature and overstress-sensitive wrinkles including dimples and labyrinth patterns are successfully induced on the resulting oxidized PDMS microspheres. A power-law dependence of the wrinkling wavelength on the microsphere radius exists. The effects of experimental parameters on these tunable spherical wrinkles have been systematically investigated, when the microspheres are pre-deposited on a substrate. These parameters include the radius and modulus of microspheres, the mixed acid solution composition, the oxidation duration, and the water washing post-treatment. Meanwhile, the complicated chemical oxidation process has also been well studied by in-situ optical observation via the microsphere system, which represents an intractable issue in a planar system. Furthermore, we realize surface wrinkled topographies on the whole microspheres at a large scale, when microspheres are directly dispersed in the mixed acid solution for surface oxidation. These results indicate that the introduced wet surface chemical oxidation has the great potential to apply to other complicated curved surfaces for large-scale generation of well-defined wrinkling patterns, which endow the solids with desired physical properties. PMID:25028198

  7. Surface Wrinkling on Polydimethylsiloxane Microspheres via Wet Surface Chemical Oxidation

    NASA Astrophysics Data System (ADS)

    Yin, Jian; Han, Xue; Cao, Yanping; Lu, Conghua

    2014-07-01

    Here we introduce a simple low-cost yet robust method to realize spontaneously wrinkled morphologies on spherical surfaces. It is based on surface chemical oxidation of aqueous-phase-synthesized polydimethylsiloxane (PDMS) microspheres in the mixed H2SO4/HNO3/H2O solution. Consequently, curvature and overstress-sensitive wrinkles including dimples and labyrinth patterns are successfully induced on the resulting oxidized PDMS microspheres. A power-law dependence of the wrinkling wavelength on the microsphere radius exists. The effects of experimental parameters on these tunable spherical wrinkles have been systematically investigated, when the microspheres are pre-deposited on a substrate. These parameters include the radius and modulus of microspheres, the mixed acid solution composition, the oxidation duration, and the water washing post-treatment. Meanwhile, the complicated chemical oxidation process has also been well studied by in-situ optical observation via the microsphere system, which represents an intractable issue in a planar system. Furthermore, we realize surface wrinkled topographies on the whole microspheres at a large scale, when microspheres are directly dispersed in the mixed acid solution for surface oxidation. These results indicate that the introduced wet surface chemical oxidation has the great potential to apply to other complicated curved surfaces for large-scale generation of well-defined wrinkling patterns, which endow the solids with desired physical properties.

  8. Metal-organic framework UiO-66 modified magnetite@silica core-shell magnetic microspheres for magnetic solid-phase extraction of domoic acid from shellfish samples.

    PubMed

    Zhang, Wenmin; Yan, Zhiming; Gao, Jia; Tong, Ping; Liu, Wei; Zhang, Lan

    2015-06-26

    Fe3O4@SiO2@UiO-66 core-shell magnetic microspheres were synthesized and characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectrometry, vibrating sample magnetometry, nitrogen adsorption porosimetry and zeta potential analyzer. The synthesized Fe3O4@SiO2@UiO-66 microspheres were first used for magnetic solid-phase extraction (MSPE) of domoic acid (DA) in shellfish samples. Combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), a fast, simple and sensitive method for the determination of DA was established successfully. Under the optimized conditions, the developed method showed short analysis time, good linearity (r(2) = 0.9990), low limit of detection (1.45 pg mL(-1); S/N = 3:1), low limit of quantification (4.82 pg mL(-1); S/N = 10:1), and good extraction repeatability (RSD ≤ 5.0%; n = 5). Real shellfish samples were processed using the developed method, and trace level of DA was detected. The results demonstrate that Fe3O4@SiO2@UiO-66 core-shell magnetic microspheres are the promising sorbents for rapid and efficient extraction of polar analytes from complex biological samples. PMID:25997847

  9. Production of hollow aerogel microspheres

    DOEpatents

    Upadhye, Ravindra S.; Henning, Sten A.

    1993-01-01

    A method is described for making hollow aerogel microspheres of 800-1200 .mu. diameter and 100-300 .mu. wall thickness by forming hollow alcogel microspheres during the sol/gel process in a catalytic atmosphere and capturing them on a foam surface containing catalyst. Supercritical drying of the formed hollow alcogel microspheres yields hollow aerogel microspheres which are suitable for ICF targets.

  10. Production of hollow aerogel microspheres

    SciTech Connect

    Upadhye, R.S.; Henning, S.A.

    1990-12-31

    A method is described for making hollow aerogel microspheres of 800--1200{mu} diameter and 100--300{mu} wall thickness by forming hollow alcogel microspheres during the sol/gel process in a catalytic atmosphere and capturing them on a foam surface containing catalyst. Supercritical drying of the formed hollow alcogel microspheres yields hollow aerogel microspheres which are suitable for ICF targets.

  11. A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

    PubMed

    Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

    2016-09-15

    A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens. PMID:27285778

  12. A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

    PubMed

    Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

    2016-09-15

    A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens.

  13. In situ growth of copper nanocrystals from carbonaceous microspheres with electrochemical glucose sensing properties

    SciTech Connect

    Zhou, Xiaoliang; Yan, Zhengguang Han, Xiaodong

    2014-02-01

    Graphical abstract: In situ growth of copper nanoparticles from hydrothermal copper-containing carbonaceous microspheres was induced by annealing or electron beam irradiation. Obtained micro-nano carbon/copper composite microspheres show electrochemical glucose sensing properties. - Highlights: • We synthesized carbonaceous microspheres containing non-nanoparicle copper species through a hydrothermal route. • By annealing or electron beam irradiation, copper nanoparticles would form from the carbonaceous microspheres in situ. • By controlling the annealing temperature, particle size of copper could be controlled in the range of 50–500 nm. • The annealed carbon/copper hierarchical composite microspheres were used to fabricate an electrochemical glucose sensor. - Abstract: In situ growth of copper nanocrystals from carbon/copper microspheres was observed in a well-controlled annealing or an electron beam irradiation process. Carbonaceous microspheres containing copper species with a smooth appearance were yielded by a hydrothermal synthesis using copper nitrate and ascorbic acid as reactants. When annealing the carbonaceous microspheres under inert atmosphere, copper nanoparticles were formed on carbon microspheres and the copper particle sizes can be increased to a range of 50–500 nm by altering the heating temperature. Similarly, in situ formation of copper nanocrystals from these carbonaceous microspheres was observed on the hydrothermal product carbonaceous microspheres with electron beam irradiation in a vacuum transmission electron microscopy chamber. The carbon/copper composite microspheres obtained through annealing were used to modify a glassy carbon electrode and tested as an electrochemical glucose sensor.

  14. Surface molecularly imprinted magnetic microspheres for the recognition of albumin.

    PubMed

    Kartal, Fatma; Denizli, Adil

    2014-08-01

    A new approach, combining metal coordination with the molecular imprinting technique, was developed to prepare affinity materials. Magnetic poly(glycidyl methacrylate) microspheres in monosize form were used for specific recognition toward the target protein. The magnetic poly(glycidyl methacrylate) microspheres were prepared by dispersion polymerization in the presence of magnetite nanopowder. Surface imprinted magnetic poly(glycidyl methacrylate) microspheres based on metal coordination were prepared and used for the selective recognition of human serum albumin. Iminodiacetic acid was used as the metal coordinating agent and human serum albumin was anchored by Cu(2+) ions on the surface of magnetic poly(glycidyl methacrylate) microspheres by metal coordination. The magnetic poly(glycidyl methacrylate) microspheres were coated with a polymer formed by condensation of tetraethyl orthosilicate and 3-aminopropyltrimethoxysilane. The human serum albumin imprinted magnetic poly(glycidyl methacrylate) microspheres were characterized by scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy and particle size analysis. The maximum adsorption capacity of human serum albumin imprinted magnetic poly(glycidyl methacrylate) microspheres was 37.7 mg/g polymer at pH 6.0. The selectivity experiments of human serum albumin imprinted magnetic poly(glycidyl methacrylate) microspheres prepared with different concentrations in the presence of lysozyme, bovine serum albumin and cytochrome C were performed in order to determine the relative selectivity coefficients.

  15. Injectable calcium hydroxylapatite microspheres (Radiesse).

    PubMed

    Ridenour, Brock; Kontis, Theda C

    2009-05-01

    Injectable calcium hydroxylapatite (Radiesse) received FDA approval in 2006 for the correction of facial lipoatrophy and moderate to severe facial wrinkles. This product consists of microspheres of a synthetic bone suspended in a methylcellulose gel matrix. Because the product is thicker than the hyaluronic acids, it is used for the correction of moderate to severe wrinkles, such as deep nasolabial folds. It is also used "off-label" to treat multiple areas of the face, nose, and hands. Radiesse is injected into the subdermal plane, and correction lasts approximately 1 year after injection.

  16. Preparation and structure of drug-carrying biodegradable microspheres designed for transarterial chemoembolization therapy.

    PubMed

    Wang, Yujing; Benzina, Abderazak; Molin, Daniel G M; Akker, Nynke van den; Gagliardi, Mick; Koole, Leo H

    2015-01-01

    Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 μm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.

  17. Organic aerogel microspheres

    DOEpatents

    Mayer, S.T.; Kong, F.M.; Pekala, R.W.; Kaschmitter, J.L.

    1999-06-01

    Organic aerogel microspheres are disclosed which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonstick gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  18. Organic aerogel microspheres

    DOEpatents

    Mayer, Steven T.; Kong, Fung-Ming; Pekala, Richard W.; Kaschmitter, James L.

    1999-01-01

    Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  19. Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy.

    PubMed

    Floyd, J Alaina; Galperin, Anna; Ratner, Buddy D

    2016-02-01

    The grim prognosis for patients diagnosed with malignant gliomas necessitates the development of new therapeutic strategies for localized and sustained drug delivery to combat tumor drug resistance and regrowth. Here we introduce drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy (DREAM BIG therapy). DREAM BIG therapy is envisioned to deliver three chemotherapeutics, temporally staged over one year, via a bioadhesive, biodegradable spray directly to the brain surgical site after tumor excision. In this proof-of-principle article exploring key components of the DREAM BIG therapy prototype, rhodamine B (RB) encapsulated poly(lactic-co-glycolic acid) and immunoglobulin G (IgG) encapsulated poly(lactic acid) microspheres were formulated and characterized. The encapsulation efficiency of RB and IgG and the release kinetics of the model drugs from the microspheres were elucidated in addition to the release kinetics of RB from poly(lactic-co-glycolic acid) microspheres formulated in a degradable poly(N-isopropylacrylamide) solution. The successful aerosolized application onto brain tissue ex-vivo demonstrated the conformal adhesion of the RB encapsulated poly(lactic-co-glycolic acid) microspheres to the convoluted brain surface mediated by the thermoresponsive carrier, poly(N-isopropylacrylamide). These preliminary results suggest the potential of the DREAM BIG therapy for future use with multiple chemotherapeutics and microsphere types to combat gliomas at a localized site. PMID:26238392

  20. Hydrophilic gallic acid-imprinted polymers over magnetic mesoporous silica microspheres with excellent molecular recognition ability in aqueous fruit juices.

    PubMed

    Hu, Xin; Xie, Lianwu; Guo, Junfang; Li, Hui; Jiang, Xinyu; Zhang, Yuping; Shi, Shuyun

    2015-07-15

    Hydrophilic molecularly imprinted polymers (MIPs) for gallic acid (GA) were prepared with excellent recognition ability in an aqueous solution. The proposed MIPs were designed by self-polymerization of dopamine (DA) on magnetic mesoporous silica (Fe3O4@SiO2@mSiO2, MMS) using GA as template. Resulting Fe3O4@SiO2@mSiO2@MIPs (MMS-MIPs) were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), vibrating sample magnetometer (VSM), and evaluated by adsorption isotherms/kinetics and competitive adsorption. The adsorption behavior between GA and MMS-MIPs followed Langmuir and Sips adsorption isotherms with a maximum adsorption capacity at 88.7 mg/g and pseudo-second-order reaction kinetics with fast binding (equilibrium time at 100 min). In addition, MMS-MIPs showed rapid magnetic separation (10 s) and stability (retained 95.2% after six cycles). Subsequently, MMS-MIPs were applied for the selective extraction and determination of GA from grape, apple, peach and orange juices (4.02, 3.91, 5.97, and 0.67 μg/g, respectively). Generally, the described method may pave the way towards rationally designing more advanced hydrophilic MIPs.

  1. Experimental Embolization of Rabbit Renal Arteries to Compare the Effects of Poly L-Lactic Acid Microspheres With and Without Epirubicin Release Against Intraarterial Injection of Epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-03-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with 1 mg of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI 1.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemoembolizing material, maintained high local concentrations of the

  2. Experimental embolization of rabbit renal arteries to compare the effects of poly L-lactic acid microspheres with and without epirubicin release against ntraarterial injection of epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-05-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with l m g of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI l.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemo-embolizing material, maintained high local concentrations of the

  3. Method for sizing hollow microspheres

    DOEpatents

    Farnum, E.H.; Fries, R.J.

    1975-10-29

    Hollow Microspheres may be effectively sized by placing them beneath a screen stack completely immersed in an ultrasonic bath containing a liquid having a density at which the microspheres float and ultrasonically agitating the bath.

  4. ENCAPSULATION OF PALLADIUM IN POROUS WALL HOLLOW GLASS MICROSPHERES

    SciTech Connect

    Heung, L; George Wicks, G; Ray Schumacher, R

    2008-04-09

    A new encapsulation method was investigated in an attempt to develop an improved palladium packing material for hydrogen isotope separation. Porous wall hollow glass microspheres (PWHGMs) were produced by using a flame former, heat treating and acid leaching. The PWHGMs were then filled with palladium salt using a soak-and-dry process. The palladium salt was reduced at high temperature to leave palladium inside the microspheres.

  5. Effects of particle size, helium gas pressure and microparticle dose on the plasma concentration of indomethacin after bombardment of indomethacin-loaded poly-L-lactic acid microspheres using a Helios gun system.

    PubMed

    Uchida, Masaki; Natsume, Hideshi; Kobayashi, Daisuke; Sugibayashi, Kenji; Morimoto, Yasunori

    2002-05-01

    We investigated the effects of the particle size of indomethacin-loaded poly-L-lactic acid microspheres (IDM-loaded PLA MS), the helium pressure used to accelerate the particles, and the bombardment dose of PLA MS on the plasma concentration of IDM after bombarding with IDM-loaded PLA MS of different particle size ranges, 20-38, 44-53 and 75-100 microm, the abdomen of hairless rats using the Helios gene gun system (Helios gun system). Using larger particles and a higher helium pressure, produced an increase in the plasma IDM concentration and the area under the plasma concentration-time curve (AUC) and resultant F (relative bioavailability with respect to intracutaneous injection) of IDM increased by an amount depending on the particle size and helium pressure. Although a reduction in the bombardment dose led to a decrease in C(max) and AUC, F increased on decreasing the bombardment dose. In addition, a more efficient F was obtained after bombarding with IDM-loaded PLA MS of 75-100 microm in diameter at each low dose in different sites of the abdomen compared with that after bolus bombardment with a high dose (dose equivalent). These results suggest that the bombardment injection of drug-loaded microspheres by the Helios gun system is a very useful tool for delivering a variety of drugs in powder form into the skin and systemic circulation.

  6. Effects of aldehydes and methods of cross-linking on properties of calcium alginate microspheres prepared by emulsification.

    PubMed

    Chan, Lai Wah; Heng, Paul W S

    2002-03-01

    Calcium alginate microspheres were prepared by an emulsification method and cross-linked with various aldehydes using different methods. Methanal and pentanedial produced low aggregation of microspheres while octanal and octadecanal produced the opposite effect. The latter two aldehydes displaced very little calcium ions from the alginate microspheres, indicating that the aggregation was due to the tackiness imparted by the aldehydes to the microsphere surface. Higuchi's model was not applicable to the drug release from microspheres in this study. The microspheres treated with methanal or pentanedial showed comparable dissolution T75% values which were significantly higher than that of the control. In contrast, octanal and octadecanal produced microspheres with lower dissolution T75% values. The drug contents of the microspheres treated with aldehydes were significantly lower than that of the control. There was insignificant interaction between the aldehydes and the drug. However, the aldehydes were found to impart acidity to the aqueous solution to varying extents, resulting in varying drug loss from the microspheres. The properties of the microspheres were also markedly affected by the method of incorporating the aldehyde. Soaking the microspheres in methanal solution produced microspheres with marked aggregation and low drug content. PMID:11808537

  7. Effects of aldehydes and methods of cross-linking on properties of calcium alginate microspheres prepared by emulsification.

    PubMed

    Chan, Lai Wah; Heng, Paul W S

    2002-03-01

    Calcium alginate microspheres were prepared by an emulsification method and cross-linked with various aldehydes using different methods. Methanal and pentanedial produced low aggregation of microspheres while octanal and octadecanal produced the opposite effect. The latter two aldehydes displaced very little calcium ions from the alginate microspheres, indicating that the aggregation was due to the tackiness imparted by the aldehydes to the microsphere surface. Higuchi's model was not applicable to the drug release from microspheres in this study. The microspheres treated with methanal or pentanedial showed comparable dissolution T75% values which were significantly higher than that of the control. In contrast, octanal and octadecanal produced microspheres with lower dissolution T75% values. The drug contents of the microspheres treated with aldehydes were significantly lower than that of the control. There was insignificant interaction between the aldehydes and the drug. However, the aldehydes were found to impart acidity to the aqueous solution to varying extents, resulting in varying drug loss from the microspheres. The properties of the microspheres were also markedly affected by the method of incorporating the aldehyde. Soaking the microspheres in methanal solution produced microspheres with marked aggregation and low drug content.

  8. Evaluation of the Intestinal Colonizing Potential and Immunomodulating Capacity of Lactobacilli Microspheres.

    PubMed

    Cotta, Karyn I; Addo, Richard T; D'Souza, Martin J

    2016-05-01

    Lactobacilli species get degraded by acidic conditions in the stomach. Thus, the objective of this study was to (1) formulate and characterize gastro-resistant Lactobacilli microspheres and (2) evaluate the ability of Lactobacilli microspheres to colonize the intestine and their capacity to have an immunomodulating effect in vivo. The product yield and the encapsulation efficiency were 45% and 100%, respectively. The average microsphere particle size was 5 μm. Lactobacilli microspheres were most stable at 4°C and showed a better suspendibility in distilled water. Without encapsulation, the viability of bacteria decreased within 30 min. In the case of Lactobacilli microspheres, no Lactobacilli were released in the first 3 h, and highest release was observed at 4 h, thus, suggesting the significance of encapsulation of Lactobacilli. Lactobacilli microspheres maintained intestinal colonization only during the dosing period, and the serum IgG, serum IgA, fecal, intestinal, nasal IgA, and the serum interleukin-1β levels were higher in the Lactobacilli microsphere group compared with the blank microsphere and the lactobacilli solution group, suggesting that the Lactobacilli microspheres were more gastro-resistant and, hence, showed positive effects compared with the Lactobacilli solution. However, the Lactobacilli microspheres did not have a significant effect on the tumor necrosis factor-α levels. PMID:27044945

  9. Evaluation of the Intestinal Colonizing Potential and Immunomodulating Capacity of Lactobacilli Microspheres.

    PubMed

    Cotta, Karyn I; Addo, Richard T; D'Souza, Martin J

    2016-05-01

    Lactobacilli species get degraded by acidic conditions in the stomach. Thus, the objective of this study was to (1) formulate and characterize gastro-resistant Lactobacilli microspheres and (2) evaluate the ability of Lactobacilli microspheres to colonize the intestine and their capacity to have an immunomodulating effect in vivo. The product yield and the encapsulation efficiency were 45% and 100%, respectively. The average microsphere particle size was 5 μm. Lactobacilli microspheres were most stable at 4°C and showed a better suspendibility in distilled water. Without encapsulation, the viability of bacteria decreased within 30 min. In the case of Lactobacilli microspheres, no Lactobacilli were released in the first 3 h, and highest release was observed at 4 h, thus, suggesting the significance of encapsulation of Lactobacilli. Lactobacilli microspheres maintained intestinal colonization only during the dosing period, and the serum IgG, serum IgA, fecal, intestinal, nasal IgA, and the serum interleukin-1β levels were higher in the Lactobacilli microsphere group compared with the blank microsphere and the lactobacilli solution group, suggesting that the Lactobacilli microspheres were more gastro-resistant and, hence, showed positive effects compared with the Lactobacilli solution. However, the Lactobacilli microspheres did not have a significant effect on the tumor necrosis factor-α levels.

  10. Method for preparing hollow metal oxide microsphere

    DOEpatents

    Schmitt, C.R.

    1974-02-12

    Hollow refractory metal oxide microspheres are prepared by impregnating resinous microspheres with a metallic compound, drying the impregnated microspheres, heating the microspheres slowly to carbonize the resin, and igniting the microspheres to remove the carbon and to produce the metal oxide. Zirconium oxide is given as an example. (Official Gazette)

  11. In vitro and in vivo characterization of biodegradable enoxacin microspheres.

    PubMed

    Abazinge, M; Jackson, T; Yang, Q; Owusu-Ababio, G

    2000-03-01

    The in vitro release and plasma concentration profiles of sustained release enoxacin microspheres intended for the treatment of bone and systemic infections due to sensitive strains of bacteria were investigated. Microspheres of enoxacin were prepared by using poly(glycolic acid-co-DL-lactic acid) (PLGA) by the emulsion solvent evaporation technique and characterized by in vitro release in an incubator, and in vivo release in the rat subcutaneous model. The microspheres were spherical in nature, and particle size range had a significant influence on the in vitro release. The enoxacin plasma concentration 2 h after the administration of treatments was two-fold higher in animals who received the free drug compared with those who received microspheres of size range 125-250 microm. The plasma of animals who received the free drug was depleted of enoxacin by the end of the first day. However, the plasma concentration of enoxacin in the animals who received microspheres was sustained above 0.5 microg/ml for about 8 days. The results show that biodegradable microspheres of enoxacin can be prepared which release the antibiotic in vivo for days following a subcutaneous administration. This should provide a means for the sustained treatment of infections due to sensitive strains of bacteria.

  12. Abiogenic Photophosphorylation of ADP to ATP Sensitized by Flavoproteinoid Microspheres

    NASA Astrophysics Data System (ADS)

    Kolesnikov, Michael P.; Telegina, Taisiya A.; Lyudnikova, Tamara A.; Kritsky, Mikhail S.

    2008-06-01

    A model for abiogenic photophosphorylation of ADP by orthophosphate to yield ATP was studied. The model is based on the photochemical activity of flavoproteinoid microspheres that are formed by aggregation in an aqueous medium of products of thermal condensation of a glutamic acid, glycine and lysine mixture (8:3:1) and contain, along with amino acid polymers (proteinoids), abiogenic isoalloxazine (flavin) pigments. Irradiation of aqueous suspensions of microspheres with blue visible light or ultraviolet in the presence of ADP and orthophosphate resulted in ATP formation. The yield of ATP in aerated suspensions was 10 20% per one mol of starting ADP. Deaeration reduced the photophosphorylating activity of microspheres five to 10 times. Treatment of aerated microsphere suspensions with superoxide dismutase during irradiation partially suppressed ATP formation. Deaerated microspheres restored completely their photophosphorylating activity after addition of hydrogen peroxide to the suspension. The photophosphorylating activity of deaerated suspensions of flavoproteinoid microspheres was also recovered by introduction of Fe3+-cytochrome c, an electron acceptor alternative to oxygen. On the basis of the results obtained, a chemical mechanism of phosphorylation is proposed in which the free radical form of reduced flavin sensitizer left( {{text{FlH}}^ bullet } right) and ADP are involved.

  13. Raspberry-like PS/CdTe/Silica Microspheres for Fluorescent Superhydrophobic Materials.

    PubMed

    Chang, Jinghui; Zang, Linlin; Wang, Cheng; Sun, Liguo; Chang, Qing

    2016-12-01

    Superhydrophobic particulate films were fabricated via deposition of raspberry-like fluorescent PS/CdTe/silica microspheres on clean glass substrates and surface modification. Particularly, the fluorescent microspheres were prepared by a kind of modified strategy, namely introducing poly (acrylic acid)-functionalized polystyrene microspheres and thiol-stabilized CdTe quantum dots into a hydrolysis reaction of tetraethoxysilane simultaneously. And through adjusting the reaction parameters, the polystyrene spheres with two particle sizes and three colors of CdTe quantum dots aqueous solution were obtained. Consequently, raspberry-like microspheres consist of polystyrene cores and the composite shells of CdTe quantum dots and silica. These microspheres possess a fluorescent characteristic and form a hierarchical dual roughness which was conductive to superhydrophobicity, and the hydrophobic tests also showed the contact angles of water droplets on the surface of the raspberry-like microspheres which were over 160° at room temperature.

  14. Raspberry-like PS/CdTe/Silica Microspheres for Fluorescent Superhydrophobic Materials

    NASA Astrophysics Data System (ADS)

    Chang, Jinghui; Zang, Linlin; Wang, Cheng; Sun, Liguo; Chang, Qing

    2016-02-01

    Superhydrophobic particulate films were fabricated via deposition of raspberry-like fluorescent PS/CdTe/silica microspheres on clean glass substrates and surface modification. Particularly, the fluorescent microspheres were prepared by a kind of modified strategy, namely introducing poly (acrylic acid)-functionalized polystyrene microspheres and thiol-stabilized CdTe quantum dots into a hydrolysis reaction of tetraethoxysilane simultaneously. And through adjusting the reaction parameters, the polystyrene spheres with two particle sizes and three colors of CdTe quantum dots aqueous solution were obtained. Consequently, raspberry-like microspheres consist of polystyrene cores and the composite shells of CdTe quantum dots and silica. These microspheres possess a fluorescent characteristic and form a hierarchical dual roughness which was conductive to superhydrophobicity, and the hydrophobic tests also showed the contact angles of water droplets on the surface of the raspberry-like microspheres which were over 160° at room temperature.

  15. Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications.

    PubMed

    Li, Wei; Jan Zaloga; Ding, Yaping; Liu, Yufang; Janko, Christina; Pischetsrieder, Monika; Alexiou, Christoph; Boccaccini, Aldo R

    2016-03-23

    The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0-87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI.

  16. Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications

    PubMed Central

    Li, Wei; Jan Zaloga; Ding, Yaping; Liu, Yufang; Janko, Christina; Pischetsrieder, Monika; Alexiou, Christoph; Boccaccini, Aldo R.

    2016-01-01

    The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0–87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI. PMID:27005428

  17. Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications

    NASA Astrophysics Data System (ADS)

    Li, Wei; Jan Zaloga; Ding, Yaping; Liu, Yufang; Janko, Christina; Pischetsrieder, Monika; Alexiou, Christoph; Boccaccini, Aldo R.

    2016-03-01

    The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0–87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI.

  18. Facile preparation of multifunctional superparamagnetic PHBV microspheres containing SPIONs for biomedical applications.

    PubMed

    Li, Wei; Jan Zaloga; Ding, Yaping; Liu, Yufang; Janko, Christina; Pischetsrieder, Monika; Alexiou, Christoph; Boccaccini, Aldo R

    2016-01-01

    The promising potential of magnetic polymer microspheres in various biomedical applications has been frequently reported. However, the surface hydrophilicity of superparamagnetic iron oxide nanoparticles (SPIONs) usually leads to poor or even failed encapsulation of SPIONs in hydrophobic polymer microspheres using the emulsion method. In this study, the stability of SPIONs in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) solution was significantly increased after surface modification with lauric acid. As a result, magnetic PHBV microspheres with high encapsulation efficiencies (71.0-87.4%) were prepared using emulsion-solvent extraction/evaporation method. Magnetic resonance imaging (MRI) showed significant contrast for the magnetic PHBV microspheres. The toxicity of these magnetic PHBV microspheres towards human T-lymphoma suspension cells and adherent colon carcinoma HT-29 cells was investigated using flow cytometry, and they were shown to be non-toxic in a broad concentration range. A model drug, tetracycline hydrochloride, was used to demonstrate the drug delivery capability and to investigate the drug release behavior of the magnetic PHBV microspheres. The drug was successfully loaded into the microspheres using lauric acid-coated SPIONs as drug carrier, and was released from the microspheres in a diffusion controlled manner. The developed magnetic PHBV microspheres are promising candidates for biomedical applications such as targeted drug delivery and MRI. PMID:27005428

  19. Polyvinyl pyridine microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1980-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  20. Polyvinyl pyridine microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

    1979-01-01

    Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

  1. Doped zinc oxide microspheres

    DOEpatents

    Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

    1993-01-01

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

  2. Doped zinc oxide microspheres

    DOEpatents

    Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

    1993-12-14

    A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

  3. Microsphere insulation systems

    NASA Technical Reports Server (NTRS)

    Allen, Mark S. (Inventor); Willen, Gary S. (Inventor); Mohling, Robert A. (Inventor)

    2005-01-01

    A new insulation system is provided that contains microspheres. This insulation system can be used to provide insulated panels and clamshells, and to insulate annular spaces around objects used to transfer, store, or transport cryogens and other temperature-sensitive materials. This insulation system provides better performance with reduced maintenance than current insulation systems.

  4. Fusion microsphere targets

    SciTech Connect

    Koo, J.C.

    1980-07-28

    It was shown that a microsphere within the structure limitations is hydrodynamically stable. To insure its perfect formation, the initial chemical compositions must have a blowing capability, more important, the resultant liquid compositions must also have sufficient surface tension and low viscosity.

  5. Release mechanisms of tacrolimus-loaded PLGA and PLA microspheres and immunosuppressive effects of the microspheres in a rat heart transplantation model.

    PubMed

    Kojima, Ryo; Yoshida, Takatsune; Tasaki, Hiroaki; Umejima, Hiroyuki; Maeda, Masashi; Higashi, Yasuyuki; Watanabe, Shunsuke; Oku, Naoto

    2015-08-15

    The objective of this study was to elucidate the release and absorption mechanisms of tacrolimus loaded into microspheres composed of poly(lactic-co-glycolic acid) (PLGA) and/or polylactic acid (PLA). Tacrolimus-loaded microspheres were prepared by the o/w emulsion solvent evaporation method. The entrapment efficiency correlated with the molecular weight of PLGA, and the glass transition temperature of PLGA microspheres was not decreased by the addition of tacrolimus. These results indicate that intermolecular interaction between tacrolimus and the polymer would affect the entrapment of tacrolimus in the microspheres. Tacrolimus was released with weight loss of the microspheres, and the dominant release mechanism of tacrolimus was considered to be erosion of the polymer rather than diffusion of the drug. The whole-blood concentration of tacrolimus in rats was maintained for at least 2 weeks after a single subcutaneous administration of the microspheres. The pharmacokinetic profile of tacrolimus following subcutaneous administration was similar to that following intramuscular administration, suggesting that the release and dissolution of tacrolimus, rather than the absorption of the dissolved tacrolimus, were rate-limiting steps. Graft-survival time in a heart transplantation rat model was prolonged by the administration of tacrolimus-loaded microspheres. The microsphere formulation of tacrolimus would be expected to precisely control the blood concentration while maintaining the immunosuppressive effect of the drug.

  6. Porous microsphere and its applications

    PubMed Central

    Cai, Yunpeng; Chen, Yinghui; Hong, Xiaoyun; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    Porous microspheres have drawn great attention in the last two decades for their potential applications in many fields, such as carriers for drugs, absorption and desorption of substances, pulmonary drug delivery, and tissue regeneration. The application of porous microspheres has become a feasible way to address existing problems. In this essay, we give a brief introduction of the porous microsphere, its characteristics, preparation methods, applications, and a brief summary of existing problems and research tendencies. PMID:23515359

  7. [Relation between drug release and the drug status within curcumin-loaded microsphere].

    PubMed

    Chen, De; Liu, Yi; Fan, Kai-yan; Xie, Yi-qiao; Yu, An-an; Xia, Zi-hua; Yang, Fan

    2016-01-01

    To study the relation between drug release and the drug status within curcumin-loaded microsphere, SPG (shirasu porous glass) membrane emulsification was used to prepare the curcumin-PLGA (polylactic-co-glycolic acid) microspheres with three levels of drug loading respectively, and the in vitro release was studied with high-performance liquid chromatography (HPLC). The morphology of microspheres was observed with scanning electron microscopy (SEM), and the drug status was studied with X-ray diffraction (XRD), differential scanning calorimetry (DSC) and infrared analysis (IR). The drug loading of microspheres was (5.85 ± 0.21)%, (11.71 ± 0.39)%, (15.41 ± 0.40)%, respectively. No chemical connection was found between curcumin and PLGA. According to the results of XRD, curcumin dispersed in PLGA as amorphous form within the microspheres of the lowest drug loading, while (2.12 ± 0.64)% and (5.66 ± 0.07)% curcumin crystals was detected in the other two kinds of microspheres, respectively, indicating that the drug status was different within three kinds of microspheres. In the data analysis, we found that PLGA had a limited capacity of dissolving curcumin. When the drug loading exceeded the limit, the excess curcumin would exist in the form of crystals in microspheres independently. Meanwhile, this factor contributes to the difference in drug release behavior of the three groups of microspheres. PMID:27405176

  8. Effects of Nano-hydroxyapatite/Poly(DL-lactic-co-glycolic acid) Microsphere-Based Composite Scaffolds on Repair of Bone Defects: Evaluating the Role of Nano-hydroxyapatite Content.

    PubMed

    He, Shu; Lin, Kai-Feng; Sun, Zhen; Song, Yue; Zhao, Yi-Nan; Wang, Zheng; Bi, Long; Liu, Jian

    2016-07-01

    The aim of the current study was to prepare microsphere-based composite scaffolds made of nano-hydroxyapatite (nHA)/poly (DL-lactic-co-glycolic acid) (PLGA) at different ratios and evaluate the effects of nHA on the characteristics of scaffolds for tissue engineering application. First, microsphere-based composite scaffolds made of two ratios of nHA/PLGA (nHA/PLGA = 20/80 and nHA/PLGA = 50/50) were prepared. Then, the effects of nHA on the wettability, mechanical strength, and degradation of scaffolds were investigated. Second, the biocompatibility and osteoinductivity were evaluated and compared by co-culture of scaffolds with bone marrow stromal stem cells (BMSCs). The results showed that the adhesion, proliferation, and osteogenic differentiation of BMSCs with nHA/PLGA (50/50) were better than those with nHA/PLGA (20/80). Finally, we implanted the scaffolds into femur bone defects in a rabbit model, then the capacity of guiding bone regeneration as well as the in vivo degradation were observed by micro-CT and histological examinations. After 4 weeks' implantation, there was no significant difference on the repair of bone defects. However, after 8 and 12 weeks' implantation, the nHA/PLGA (20/80) exhibited better bone formation than nHA/PLGA (50/50). These results suggested that a proper concentration of nHA in the nHA/PLGA composite should be taken into account when the composite scaffolds were prepared, which plays an important role in the biocompatibility, degradation rate and osteoconductivity.

  9. Functional magnetic microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Landel, Robert F. (Inventor)

    1981-01-01

    Functional magnetic particles are formed by dissolving a mucopolysaccharide such as chitosan in acidified aqueous solution containing a mixture of ferrous chloride and ferric chloride. As the pH of the solution is raised magnetite is formed in situ in the solution by raising the pH. The dissolved chitosan is a polyelectrolyte and forms micelles surrounding the granules at pH of 8-9. The chitosan precipitates on the granules to form microspheres containing the magnetic granules. On addition of the microspheres to waste aqueous streams containing dissolved ions, the hydroxyl and amine functionality of the chitosan forms chelates binding heavy metal cations such as lead, copper, and mercury and the chelates in turn bind anions such as nitrate, fluoride, phosphate and borate.

  10. Formulation and in vitro evaluation of rifampicin loaded porous microspheres.

    PubMed

    Bhise, Satish Balakrishna; More, Avinash Bhanudas; Malayandi, Rajkumar

    2010-01-01

    Rifampicin (RIF) is a major component in fixed dose combination therapy for the treatment of tuberculosis. RIF has low solubility and high permeability with high dose and hence it is classified as class II drug in Biopharmaceutical Classification System (BCS). RIF has poor and variable bioavailability because of its poor solubility, acid decomposition and, drug and food interaction. The present investigation was aimed to develop RIF loaded porous microspheres as a controlled release dosage form. Eudragit based porous microspheres of RIF were prepared by emulsion solvent diffusion method. Prepared porous microspheres were evaluated for its entrapment efficacy, morphology, thermal behavior, crystalline nature, in-vitro drug release and stability in simulated gastric fluid. The entrapment efficacy of drug loaded microspheres was found to be in the range of 19.04â74.57%. Surface morphology revealed the porous and spherical structure of microspheres. Differential scanning calorimetric studies confirmed that formulation process altered the crystalline nature of RIF. In vitro drug release studies indicated that drug to polymer ratio of 2:1 showed more than 85% drug release over the period of 3 h. Stability studies in simulated gastric fluid (SGF) indicated that low relative decomposition of 18.5% was achieved with high drug to low polymer ratio of 1:4. The results obtained from the present investigation concluded that RIF loaded porous microspheres are suitable for developing oral controlled release dosage form of RIF that can prevent acid decomposition and provide better biopharmaceutical properties. Further more the microspheres can be evaluated for preventing the interaction with isoniazid, other drugs and foodstuffs.

  11. Coacervate-like microspheres from lysine-rich proteinoid

    NASA Technical Reports Server (NTRS)

    Rohlfing, D. L.

    1975-01-01

    Microspheres form isothermally from lysine-rich proteinoid when the ionic strength of the solution is increased with NaCl or other salts. Studies with different monovalent anions and with polymers of different amino acid composition indicate that charge neutralization and hydrophobic bonding contribute to microsphere formation. The particles also form in sea water, especially if heated or made slightly alkaline. The microspheres differ from those made from acidic proteinoid but resemble coacervate droplets in some ways (isothermal formation, limited stability, stabilization by quinone, uptake of dyes). Because the constituent lysine-rich proteinoid is of simulated prebiotic origin, the study is interpreted to add emphasis to and suggest an evolutionary continuity for coacervation phenomena.

  12. Trading polymeric microspheres: exchanging DNA molecules via microsphere interaction.

    PubMed

    Morimoto, Nobuyuki; Muramatsu, Kanna; Nomura, Shin-ichiro M; Suzuki, Makoto

    2015-04-01

    A new class of artificial molecular transport system is constructed by polymeric microspheres. The microspheres are prepared by self-assembly of poly(ethylene glycol)-block-poly(3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate), PEG-b-PDMAPS, by intermolecular dipole-dipole interaction of sulfobetaine side chains in water. Below the upper critical solution temperature (UCST) of PEG-b-PDMAPS, the microspheres (∼1μm) interact with other microspheres by partial and transit fusion. In order to apply the interaction between microspheres, a 3'-TAMRA-labeled single-stranded DNA oligomer (ssDNA) is encapsulated into a PEG-b-PDMAPS microsphere by thermal treatment. The exchange of ssDNA between microspheres is confirmed by fluorescence resonance energy transfer (FRET) quenching derived from double-stranded formation with complementary 5'-BHQ-2-labeled ssDNA encapsulated in PEG-b-PDMAPS microspheres. The exchange rate of ssDNA is controllable by tuning the composition of the polymer. The contact-dependent transport of molecules can be applied in the areas of microreactors, sensor devices, etc. PMID:25731098

  13. Trading polymeric microspheres: exchanging DNA molecules via microsphere interaction.

    PubMed

    Morimoto, Nobuyuki; Muramatsu, Kanna; Nomura, Shin-ichiro M; Suzuki, Makoto

    2015-04-01

    A new class of artificial molecular transport system is constructed by polymeric microspheres. The microspheres are prepared by self-assembly of poly(ethylene glycol)-block-poly(3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate), PEG-b-PDMAPS, by intermolecular dipole-dipole interaction of sulfobetaine side chains in water. Below the upper critical solution temperature (UCST) of PEG-b-PDMAPS, the microspheres (∼1μm) interact with other microspheres by partial and transit fusion. In order to apply the interaction between microspheres, a 3'-TAMRA-labeled single-stranded DNA oligomer (ssDNA) is encapsulated into a PEG-b-PDMAPS microsphere by thermal treatment. The exchange of ssDNA between microspheres is confirmed by fluorescence resonance energy transfer (FRET) quenching derived from double-stranded formation with complementary 5'-BHQ-2-labeled ssDNA encapsulated in PEG-b-PDMAPS microspheres. The exchange rate of ssDNA is controllable by tuning the composition of the polymer. The contact-dependent transport of molecules can be applied in the areas of microreactors, sensor devices, etc.

  14. Protein complexed with chondroitin sulfate in poly(lactide-co-glycolide) microspheres.

    PubMed

    Lee, Eun Seong; Park, Keun-Hong; Kang, Dongmin; Park, In Suh; Min, Hyo Young; Lee, Don Haeng; Kim, Sungwon; Kim, Jong Ho; Na, Kun

    2007-06-01

    Chondroitin sulfate (CsA) is an acidic mucopolysaccharide, which is able to form ionic complexes with positively charged proteins. In this study, a protein-CsA complex was constructed to nano-sized particles. Zeta potential measurements revealed that a CsA-to-protein fraction of greater than 0.1 results in a neutralization of the positive charge on lysozyme (Lys). Based on this preliminary study, we have prepared poly(lactide-co-glycolide) (PLGA) microspheres harboring Lys/CsA complexes via the multi-emulsion method. Protein stability in the PLGA microspheres was preserved during both microsphere preparation and protein release. The profiles of Lys release from the PLGA microspheres evidenced nearly zero-order kinetics, depending on the quantity of CsA. An in vivo fluorescent image of experimental mouse tissue showed that the PLGA microspheres with the Lys/CsA complex had released the entirety of their Lys without no residual amount after 23 days, but microspheres without the complex harbored a great deal of residual Lys, which is attributable to its degradation by acidic PLGA degradates. The tissue reaction evidenced by the PLGA microspheres stabilized with CsA showed minimal foreign body reaction and little configuration of immune cells including neutrophils and macrophages, but the reactions of the PLGA microspheres without CsA were characterized by a relatively elevated inflammation. These results show that CsA is a viable candidate for long-acting micro-particular protein delivery. PMID:17337049

  15. Metal containing polymeric functional microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

    1979-01-01

    Polymeric functional microspheres containing metal or metal compounds are formed by addition polymerization of a covalently bondable olefinic monomer such as hydroxyethylmethacrylate in the presence of finely divided metal or metal oxide particles, such as iron, gold, platinum or magnetite, which are embedded in the resulting microspheres. The microspheres can be covalently bonded to chemotherapeutic agents, antibodies, or other proteins providing a means for labeling or separating labeled cells. Labeled cells or microspheres can be concentrated at a specific body location such as in the vicinity of a malignant tumor by applying a magnetic field to the location and then introducing the magnetically attractable microspheres or cells into the circulatory system of the subject. Labeled cells can be separated from a cell mixture by applying a predetermined magnetic field to a tube in which the mixture is flowing. After collection of the labeled cells, the magnetic field is discontinued and the labeled sub-cell population recovered.

  16. Immunofluorescence detection methods using microspheres

    NASA Astrophysics Data System (ADS)

    Szurdoki, Ferenc; Michael, Karri L.; Agrawal, Divya; Taylor, Laura C.; Schultz, Sandra L.; Walt, David R.

    1999-01-01

    Microsphere-based immunoassays were devised for compounds of agricultural and biomedical interest (e.g., digoxin, theophylline, and zearalenone). Commercially available microspheres with surface functional groups for chemical derivatization were used as solid carriers. After immobilizing the target substances, the surface of the haptenized microspheres was blocked by a protein to reduce aspecific binding. Competitive immunoassays were performed using the functionalized microspheres and antibodies labeled with horseradish peroxidase. Immunofluorescence signal amplification was achieved by enzyme-catalyzed reporter deposition (CARD). An epifluorescence microscope, a CCD camera interfaced with a computer, and microscopy image analysis software were employed for quantitative detection of fluorescent light emitted from individual microspheres. Integration of several such immunoassays and application of an optical encoding method enabled multianalyte determination. These immunoassays can also be utilized in an immunosensor array format. This immunoarray format could facilitate miniaturization and automation of multianalyte immunoassays.

  17. Covalent TiO(2)/pectin microspheres with Fe(3)O(4) nanoparticles for magnetic field-modulated drug delivery.

    PubMed

    da Silva, Elisangela P; Sitta, Danielly L A; Fragal, Vanessa H; Cellet, Thelma S P; Mauricio, Marcos R; Garcia, Francielle P; Nakamura, Celso V; Guilherme, Marcos R; Rubira, Adley F; Kunita, Marcos H

    2014-06-01

    Covalent TiO(2)-co-pectin microspheres containing Fe(3)O(4) nanoparticles were developed through an ultrasound-induced crosslinking/polymerization reaction between the glycidyl methacrylate from vinyl groups in TiO(2) and in pectin. ζ-potentials became less negative in the nanostructured microspheres, caused by the presence of both inorganic particles in the negatively charged pectin. The nanostructured pectin microspheres showed an amoxicillin release rate slower than that of pure pectin microspheres. The proposed microspheres were found to be a sustained release system of amoxicillin in the acid medium. Furthermore, the antibiotic release may be modulated by exposition of the microspheres to a remote magnetic field. In practical terms, the nanostructured microspheres could deliver a larger proportion of their initial load to specific site of action. The cytotoxic concentrations for 50% of VERO cells (CC(50)), calculated as the concentration required to reduce cell viability by 50% after 72h of incubation, for pectin-only microspheres and nanostructured pectin microspheres were 217.7±6.5 and 121.5±4.9μgmL(-1), respectively. The obtained CC(50) values indicated acceptable cytotoxic levels for an incubation period of 72h, showing that the pectin microspheres have a great pharmacological potential for uses in biological environments, even after the introduction of both Fe(3)O(4) and TiO(2). PMID:24565898

  18. Covalent TiO(2)/pectin microspheres with Fe(3)O(4) nanoparticles for magnetic field-modulated drug delivery.

    PubMed

    da Silva, Elisangela P; Sitta, Danielly L A; Fragal, Vanessa H; Cellet, Thelma S P; Mauricio, Marcos R; Garcia, Francielle P; Nakamura, Celso V; Guilherme, Marcos R; Rubira, Adley F; Kunita, Marcos H

    2014-06-01

    Covalent TiO(2)-co-pectin microspheres containing Fe(3)O(4) nanoparticles were developed through an ultrasound-induced crosslinking/polymerization reaction between the glycidyl methacrylate from vinyl groups in TiO(2) and in pectin. ζ-potentials became less negative in the nanostructured microspheres, caused by the presence of both inorganic particles in the negatively charged pectin. The nanostructured pectin microspheres showed an amoxicillin release rate slower than that of pure pectin microspheres. The proposed microspheres were found to be a sustained release system of amoxicillin in the acid medium. Furthermore, the antibiotic release may be modulated by exposition of the microspheres to a remote magnetic field. In practical terms, the nanostructured microspheres could deliver a larger proportion of their initial load to specific site of action. The cytotoxic concentrations for 50% of VERO cells (CC(50)), calculated as the concentration required to reduce cell viability by 50% after 72h of incubation, for pectin-only microspheres and nanostructured pectin microspheres were 217.7±6.5 and 121.5±4.9μgmL(-1), respectively. The obtained CC(50) values indicated acceptable cytotoxic levels for an incubation period of 72h, showing that the pectin microspheres have a great pharmacological potential for uses in biological environments, even after the introduction of both Fe(3)O(4) and TiO(2).

  19. Polysaccharide-based aerogel microspheres for oral drug delivery.

    PubMed

    García-González, C A; Jin, M; Gerth, J; Alvarez-Lorenzo, C; Smirnova, I

    2015-03-01

    Polysaccharide-based aerogels in the form of microspheres were investigated as carriers of poorly water soluble drugs for oral administration. These bio-based carriers may combine the biocompatibility of polysaccharides and the enhanced drug loading capacity of dry aerogels. Aerogel microspheres from starch, pectin and alginate were loaded with ketoprofen (anti-inflammatory drug) and benzoic acid (used in the management of urea cycle disorders) via supercritical CO2-assisted adsorption. Amount of drug loaded depended on the aerogel matrix structure and composition and reached values up to 1.0×10(-3) and 1.7×10(-3) g/m(2) for ketoprofen and benzoic acid in starch microspheres. After impregnation, drugs were in the amorphous state in the aerogel microspheres. Release behavior was evaluated in different pH media (pH 1.2 and 6.8). Controlled drug release from pectin and alginate aerogel microspheres fitted Gallagher-Corrigan release model (R(2)>0.99 in both cases), with different relative contribution of erosion and diffusion mechanisms depending on the matrix composition. Release from starch aerogel microspheres was driven by dissolution, fitting the first-order kinetics due to the rigid starch aerogel structure, and showed different release rate constant (k1) depending on the drug (0.075 and 0.160 min(-1) for ketoprofen and benzoic acid, respectively). Overall, the results point out the possibilities of tuning drug loading and release by carefully choosing the polysaccharide used to prepare the aerogels.

  20. In vitro-in vivo correlation of parenteral risperidone polymeric microspheres.

    PubMed

    Shen, Jie; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

    2015-11-28

    The objective of the present study was to determine whether an in vitro-in vivo correlation (IVIVC) can be established for polymeric microspheres that are equivalent in formulation composition but prepared with different manufacturing processes. Risperidone was chosen as a model therapeutic and poly(lactic-co-glycolic acid) (PLGA) with similar molecular weight as that used in the commercial product Risperdal® Consta® was used to prepare risperidone microspheres. Various manufacturing processes were investigated to produce the risperidone microspheres with similar drug loading (approx. 37%) but distinctly different physicochemical properties (e.g. porosity, particle size and particle size distribution). In vitro release of the risperidone microspheres was investigated using different release testing methods (such as sample-and-separate and USP apparatus 4). In vivo pharmacokinetic profiles of the risperidone microsphere formulations following intramuscular administration were determined using a rabbit model. Furthermore, the obtained pharmacokinetic profiles were deconvoluted using the Loo-Riegelman method and the calculated in vivo release was compared with the in vitro release of these microspheres. Level A IVIVCs were established and validated for the compositionally equivalent risperidone microspheres based on the in vitro release data obtained using USP apparatus 4. The developed IVIVCs demonstrated good predictability and were robust. These results showed that the developed USP apparatus 4 method was capable of discriminating PLGA microspheres that are equivalent in formulation composition but with manufacturing differences and predicting their in vivo performance in the investigated animal model.

  1. Preliminary results on a new method for producing yttrium phosphorous microspheres.

    PubMed

    Ghahramani, M R; Garibov, A A; Agayev, T N

    2014-09-01

    This paper reports on a new method to embed phosphorus particles into the matrix of yttrium aluminum silicate microspheres. Yttrium phosphorus glass microspheres about 20µm in size were obtained when an aqueous solution of YCl3 and AlCl3 were added to tetraethyl orthosilicate (TEOS) (phosphoric acid was used to catalyze the hydrolysis and condensation of TEOS) and was pumped into silicone oil under constant stirring. The shapes of the particles produced by this method are regular and nearly spheric in shape. Paper chromatography was used to determine the radiochemical impurity of radioactive microspheres. Radionuclide purity was determined using a gamma spectrometry system and an ultra-low level liquid scintillation spectrometer. The P(+) ions implantation stage was eliminated by embedding phosphorus particles in the matrix of the glass microspheres. This paper shows that a high temperature is not required to produce yttrium phosphorus aluminum silicate microspheres. The result shows that the silicone oil spheroidization method is a very suitable way to produce yttrium phosphorus glass microspheres. The topographical analysis of microspheres shows that the Y, P, Si, and Al elements are distributed in the microspheres and the distribution of elements in the samples is homogenous.

  2. Process and formulation variables in the preparation of injectable and biodegradable magnetic microspheres

    PubMed Central

    Zhao, Hong; Gagnon, Jeffrey; Häfeli, Urs O

    2007-01-01

    The aim of this study was to prepare biodegradable sustained release magnetite microspheres sized between 1 to 2 μm. The microspheres with or without magnetic materials were prepared by a W/O/W double emulsion solvent evaporation technique using poly(lactide-co-glycolide) (PLGA) as the biodegradable matrix forming polymer. Effects of manufacturing and formulation variables on particle size were investigated with non-magnetic microspheres. Microsphere size could be controlled by modification of homogenization speed, PLGA concentration in the oil phase, oil phase volume, solvent composition, and polyvinyl alcohol (PVA) concentration in the outer water phase. Most influential were the agitation velocity and all parameters that influence the kinematic viscosity of oil and outer water phase, specifically the type and concentration of the oil phase. The magnetic component yielding homogeneous magnetic microspheres consisted of magnetite nanoparticles of 8 nm diameter stabilized with a polyethylene glycole/polyacrylic acid (PEG/PAA) coating and a saturation magnetization of 47.8 emu/g. Non-magnetic and magnetic microspheres had very similar size, morphology, and size distribution, as shown by scanning electron microscopy. The optimized conditions yielded microspheres with 13.7 weight% of magnetite and an average diameter of 1.37 μm. Such biodegradable magnetic microspheres seem appropriate for vascular administration followed by magnetic drug targeting. PMID:17407608

  3. RANKL delivery from calcium phosphate containing PLGA microspheres.

    PubMed

    Félix Lanao, Rosa P; Bosco, Ruggero; Leeuwenburgh, Sander C G; Kersten-Niessen, Monique J F; Wolke, Joop G C; van den Beucken, Jeroen J J P; Jansen, John A

    2013-11-01

    Ideally, bone substitute materials would undergo cell-mediated degradation during the remodeling process of the host bone tissue while being replaced by newly formed bone. In an attempt to exploit the capacity of Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) to stimulate osteoclast-like cells formation, this study explored different loading methods for RANKL in injectable calcium phosphate cement (CPC) and the effect on release and biological activity. RANKL was loaded via the liquid phase of CPC by adsorption onto or incorporation into poly(lactic-co-glycolic acid) (PLGA) microspheres with two different morphologies (i.e., hollow and dense), which were subsequently embedded in CPC. As controls nonembedded PLGA-microspheres were used as well as plain CPC scaffolds with RANKL adsorbed onto the surface. RANKL release and activity were evaluated by Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) and osteoclast-like cells formation in cell culture experiments. Results indicated that sustained release of active RANKL can be achieved upon RANKL adsorption to PLGA microspheres, whereas inactive RANKL was released from CPC-PLGA formulations with RANKL incorporated within the microspheres or within the liquid phase of the CPC. These results demonstrate that effective loading of RANKL in injectable CPC is only possible via adsorption to PLGA microspheres, which are subsequently embedded within the CPC-matrix.

  4. Thrombin receptor agonist Peptide immobilized in microspheres stimulates reparative processes in rats with gastric ulcer.

    PubMed

    Rusanova, A V; Makarova, A M; Strukova, S M; Markvicheva, E A; Gorbachyova, L R; Stashevskaya, K S; Vasil'eva, T V; Sidorova, E I; Bespalova, Zh D; Grandfils, Ch

    2006-07-01

    The effect of synthetic thrombin receptor (PAR1) agonist peptide encapsulated in microspheres made of lactic and glycolic acid copolymer on tissue reparation was studied in rats with acetate-induced ulcer. PAR1 agonist peptide was immobilized in biodegraded lactic and glycolic acid microspheres by double emulgation, the kinetics of peptide release was analyzed, and the dynamics of ulcer healing was studied in experimental (administration of microspheres with the peptide into the stomach) and two control groups (administration of saline or spheres without peptide). Thrombin receptor agonist peptide gradually released from lactic and glycolic acid microspheres into the stomach shortened the inflammation phase and shifted the proliferation phase to the earlier period, thus accelerating healing of experimental ulcers in rats. PMID:17369897

  5. Towards Monodispersed Polymer Microspheres

    NASA Astrophysics Data System (ADS)

    Senuma, Yoshinori; Hilborn, Jons

    1998-03-01

    Uniform polymer microspheres prepared by Spinning Disk Atomization Our spinning disk atomization (SDA) can, relative to other existing techniques, produce micron-sized particles of very narrow size distribution. Around the edge of the disk, small teeth channel the flow into identical droplets that are flung off over the disk rim. These solidify during flight to form spherical particles. Applications for spheres produced by SDA can be found in areas such as adhesives, powder coatings, food, biomedical use, drug delivery systems, etc. We have atomized polyethyleneglycol into very narrowly dispersed microspheres ranging from 50 to 500 =B5m. The aim of this work is to model the droplet formation occurring at the rim of the spinning disk in order to better understand the experimental results. The viscosity contribution in the fluid breakup is qualitatively analyzed and is adapted to the theoretical model to show how it affects the droplet size. We have used the pendant drop model (Ramesh Babu, S. Journal of Colloid and Interface Science 116, 350-372 (1987).) for spinning disk atomization to describe the drop-shape evolution during growth.

  6. Convective microsphere monolayer deposition

    NASA Astrophysics Data System (ADS)

    Gilchrist, James

    2011-03-01

    There is perhaps no simpler way of modifying surface chemistry and morphology than surface deposition of particles. Micron-sized microspheres were deposited into thin films via rapid convective deposition, similar to the `coffee ring effect' using a similar method to that studied by Prevo and Velev, Langmuir, 2003. By varying deposition rate and blade angle, the optimal operating ranges in which 2D close-packed arrays of microspheres existed were obtained. Self-assembly of colloidal particles through a balance of electrostatic and capillary forces during solvent evaporation was revealed. These interactions were explored through a model comparing the residence time of a particle in the thin film and the characteristic time of capillary-driven crystallization to describe the morphology and microstructure of deposited particles. Co-deposition of binary suspensions of micron and nanoscale particles was tailored to generate higher-quality surface coatings and a simple theory describes the immergence of instabilities that result in formation of stripes. Optical and biomedical applications that utilize the described nanoscale control over surface morphology will also be discussed.

  7. Microsphere based saliva diagnostics

    NASA Astrophysics Data System (ADS)

    Rissin, David M.; DiCesare, Christopher; Hayman, Ryan B.; Blicharz, Timothy M.; Walt, David R.

    2005-11-01

    Saliva presents a minimally invasive alternative medium to blood for performing diagnostics1. Microsphere sensors for ions, small organic molecules, and proteins are currently being developed and optical microarrays containing thousands of these sensors will be used for simultaneous multi-analyte analysis. The fiber bundle platform in use is 1mm in diameter and contains approximately 50,000 individually addressable 3.1μm fibers, each with an etched well capable of housing a single 3.1μm microsphere sensor. Micron-sized bead-based chemistries are produced in house, followed by deposition onto a fiber-optic bundle platform, allowing for multiplexed analysis. The ultimate goal is to develop a universal diagnostic system using saliva as the diagnostic medium. This platform will permit multiplexed analysis of a sample by integrating microfluidics with the optical arrays loaded with sensors capable of detecting relevant biomarkers associated with a wide range of disease states. Disease states that are currently under investigation include end stage renal disease (ESRD) and Sjoegrens Syndrome (SS).

  8. Glass microsphere lubrication

    NASA Technical Reports Server (NTRS)

    Geiger, Michelle; Goode, Henry; Ohanlon, Sean; Pieloch, Stuart; Sorrells, Cindy; Willette, Chris

    1991-01-01

    The harsh lunar environment eliminated the consideration of most lubricants used on earth. Considering that the majority of the surface of the moon consists of sand, the elements that make up this mixture were analyzed. According to previous space missions, a large portion of the moon's surface is made up of fine grained crystalline rock, about 0.02 to 0.05 mm in size. These fine grained particles can be divided into four groups: lunar rock fragments, glasses, agglutinates (rock particles, crystals, or glasses), and fragments of meteorite material (rare). Analysis of the soil obtained from the missions has given chemical compositions of its materials. It is about 53 to 63 percent oxygen, 16 to 22 percent silicon, 10 to 16 percent sulfur, 5 to 9 percent aluminum, and has lesser amounts of magnesium, carbon, and sodium. To be self-supporting, the lubricant must utilize one or more of the above elements. Considering that the element must be easy to extract and readily manipulated, silicon or glass was the most logical choice. Being a ceramic, glass has a high strength and excellent resistance to temperature. The glass would also not contaminate the environment as it comes directly from it. If sand entered a bearing lubricated with grease, the lubricant would eventually fail and the shaft would bind, causing damage to the system. In a bearing lubricated with a solid glass lubricant, sand would be ground up and have little effect on the system. The next issue was what shape to form the glass in. Solid glass spheres was the only logical choice. The strength of the glass and its endurance would be optimal in this form. To behave as an effective lubricant, the diameter of the spheres would have to be very small, on the order of hundreds of microns or less. This would allow smaller clearances between the bearing and the shaft, and less material would be needed. The production of glass microspheres was divided into two parts, production and sorting. Production includes the

  9. Macrocyclic amine-linked oligocarbazole hollow microspheres: facile synthesis and efficient lead sorbents.

    PubMed

    Liao, Yaozu; Cai, Sisi; Huang, Shaojun; Wang, Xia; Faul, Charl F J

    2014-11-01

    Novel macrocyclic amine-linked oligocarbazole hollow microspheres are synthesized via a one-step oxidative method in aqueous solution. Upon altering the oxidants and acidic media, the average diameters of the obtained hollow microspheres are tunable from 0.23 to 2.0 μm. With attractive amine and carbazole functionalities, exposed surface area, thermostability, and photoluminescent properties, the amine-linked oligocarbazole hollow microspheres are directly assembled to yield heavy metal sorbents with excellent selectivity and recyclability, shown to efficiently remove lead from contaminated water.

  10. Recombinant human bone morphogenetic protein-2 binding and incorporation in PLGA microsphere delivery systems.

    PubMed

    Schrier, J A; DeLuca, P P

    1999-01-01

    The objective of this research was to determine the binding capacity and kinetics, and total incorporation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in microspheres made from hydrophilic and hydrophobic poly(lactide-co-glycolide) (PLGA). Polymers were characterized by molecular weight, polydispersity, and acid number. Microspheres were produced via a water-in-oil-in-water double emulsion system and characterized for bulk density, size, specific surface area, and porosity. Protein concentrations were determined by reversed phase HPLC. Protein was loaded by soaking microspheres in a buffered solution, pH 4.5, of rhBMP-2, decanting excess liquid, and vacuum drying the wetted particles. Total loading and binding were determined by comparing protein concentration remaining to non-microsphere containing samples. Polymer acid number was the dominant polymer feature affecting the binding. Higher acid values correlated with increased rhBMP-2 binding. The amount of non-bound incorporated rhBMP-2 linearly correlated with the concentration of protein used in binding. High rhBMP-2 concentrations inhibit binding to PLGA microspheres. Binding was also inhibited by increased lactide content in the PLGA polymer. The polymer characteristics controlling rhBMP-2 binding to PLGA microspheres are acid value foremost followed by molecular weight and lactide/glycolide ratio. The total amount of rhBMP-2 incorporated depends on the bound amount and on the amount of free protein present.

  11. A short term quality control tool for biodegradable microspheres.

    PubMed

    D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

    2014-06-01

    Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C. PMID:24519488

  12. Cephradin-plaga microspheres for sustained delivery to cattle.

    PubMed

    Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramé, B

    1999-01-01

    In the field of controlled drug delivery, most of the reported work is aimed at introducing new systems, or at providing basic information on the critical parameters which affect release profiles in vitro and occasionally in vivo. The situation is totally different when one wants to fulfil the specific requirements imposed by the marketing of a sustained release device to be used in humans or in animals eaten by human beings. The control of the release characteristics is then a difficult challenge. In this work, attempts were made to combine cephradin, a hydrophilic beta-lactam antibiotic, and bioresorbable polymeric matrices of a poly(alpha-hydroxy acid) in the form of microspheres with the aim of delivering the antibiotic to cattle at a dose rate of 4-5 mg/kg/day over a 3-4 days period after i.m. injection. PLAGA aliphatic polyesters were selected because they are already FDA approved as matrices. The solvent evaporation technique using PVA as the emulsion stabilizer was selected because it is efficient and can be extended to an industrial scale. Various experimental conditions were used in order to obtain the highest encapsulation yields compatible with the desired specifications. Decreasing the volume of the aqueous phase and adding a water-miscible organic solvent/non-solvent of cephradin failed. In contrast, microspheres containing up to 30% cephradin were prepared after addition of sodium chloride to the aqueous dispersing phase. The amount of entrapped drug was raised to 40% by decreasing the temperature and the pressure. Preliminary investigations using dogs showed that 20% cephradin microspheres prepared under these conditions extended the presence of cephradin in the blood circulation up to 48 h. Increasing the load led to higher blood concentrations but shorter sustained release. The fact that the microspheres were for cattle limited the volume of the injection and thus the amount of microspheres to be administered. The other limiting factors were

  13. A short term quality control tool for biodegradable microspheres.

    PubMed

    D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

    2014-06-01

    Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.

  14. Coaxial electrohydrodynamic atomization process for production of polymeric composite microspheres

    PubMed Central

    Xu, Qingxing; Qin, Hao; Yin, Zhenyuan; Hua, Jinsong; Pack, Daniel W.; Wang, Chi-Hwa

    2013-01-01

    Polymeric composite microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer were successfully fabricated by coaxial electrohydrodynamic atomization (CEHDA) process. Process conditions, including nozzle voltage and polymer solution flow rates, as well as solution parameters, such as polymer concentrations, were investigated to ensure the formation of composite microspheres with a doxorubicin-loaded PLGA core surrounded by a relatively drug-free PDLLA shell layer. Various microsphere formulations were fabricated and characterized in terms of their drug distribution, encapsulation efficiency and in vitro release. Numerical simulation of CEHDA process was performed based on a computational fluid dynamics (CFD) model in Fluent by employing the process conditions and fluid properties used in the experiments. The simulation results were compared with the experimental work to illustrate the capability of the CFD model to predict the production of consistent compound droplets, and hence, the expected core-shell structured microspheres. PMID:24347672

  15. Coaxial electrohydrodynamic atomization process for production of polymeric composite microspheres.

    PubMed

    Xu, Qingxing; Qin, Hao; Yin, Zhenyuan; Hua, Jinsong; Pack, Daniel W; Wang, Chi-Hwa

    2013-12-18

    Polymeric composite microspheres consisting of a poly(D,L-lactic-co-glycolic acid) (PLGA) core surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer were successfully fabricated by coaxial electrohydrodynamic atomization (CEHDA) process. Process conditions, including nozzle voltage and polymer solution flow rates, as well as solution parameters, such as polymer concentrations, were investigated to ensure the formation of composite microspheres with a doxorubicin-loaded PLGA core surrounded by a relatively drug-free PDLLA shell layer. Various microsphere formulations were fabricated and characterized in terms of their drug distribution, encapsulation efficiency and in vitro release. Numerical simulation of CEHDA process was performed based on a computational fluid dynamics (CFD) model in Fluent by employing the process conditions and fluid properties used in the experiments. The simulation results were compared with the experimental work to illustrate the capability of the CFD model to predict the production of consistent compound droplets, and hence, the expected core-shell structured microspheres.

  16. Fabrication of glass microspheres with conducting surfaces

    DOEpatents

    Elsholz, William E.

    1984-01-01

    A method for making hollow glass microspheres with conducting surfaces by adding a conducting vapor to a region of the glass fabrication furnace. As droplets or particles of glass forming material pass through multiple zones of different temperature in a glass fabrication furnace, and are transformed into hollow glass microspheres, the microspheres pass through a region of conducting vapor, forming a conducting coating on the surface of the microspheres.

  17. Fabrication of glass microspheres with conducting surfaces

    DOEpatents

    Elsholz, W.E.

    1982-09-30

    A method for making hollow glass microspheres with conducting surfaces by adding a conducting vapor to a region of the glass fabrication furnace. As droplets or particles of glass forming material pass through multiple zones of different temperature in a glass fabrication furnace, and are transformed into hollow glass microspheres, the microspheres pass through a region of conducting vapor, forming a conducting coating on the surface of the microspheres.

  18. On-demand one-step synthesis of monodisperse functional polymeric microspheres with droplet microfluidics.

    PubMed

    Yu, Xu; Cheng, Gong; Zhou, Ming-Da; Zheng, Si-Yang

    2015-04-01

    A simple and robust method for one-step synthesis of monodisperse functional polymeric microspheres was established by generation of reversed microemulsion droplets in aqueous phase inside microfluidic chips and controlled evaporation of the organic solvent. Using this method, water-soluble nanomaterials can be easily encapsulated into biodegradable Poly(D,L-lactic-co-glycolic acid) (PLGA) to form functional microspheres. By controlling the flow rate of microemulsion phase, PLGA polymeric microspheres with narrow size distribution and diameters in the range of ∼50-100 μm were obtained. As a demonstration of the versatility of the approach, high-quality fluorescent CdTe:Zn(2+) quantum dots (QDs) of various emission spectra, superparamagnetic Fe3O4 nanoparticles, and water-soluble carbon nanotubes (CNTs) were used to synthesize fluorescent PLGA@QDs, magnetic PLGA@Fe3O4, and PLGA@CNTs polymeric microspheres, respectively. In order to show specific applications, the PLGA@Fe3O4 were modified with polydopamine (PDA), and then the silver nanoparticles grew on the surfaces of the PLGA@Fe3O4@PDA polymeric microspheres by reducting the Ag(+) to Ag(0). The as-prepared PLGA@Fe3O4@PDA-Ag microspheres showed a highly efficient catalytic reduction of the 4-nitrophenol, a highly toxic substance. The monodisperse uniform functional PLGA polymeric microspheres can potentially be critically important for multiple biomedical applications.

  19. Bacterial protease triggered release of biocides from microspheres with an oily core.

    PubMed

    Craig, Marina; Amiri, Mona; Holmberg, Krister

    2015-03-01

    This study deals with controlled release of drugs to a Staphylococcus aureus infected site from microspheres with an oily core and a polymeric shell. The intended use of the microspheres is for chronic wounds and the microspheres may be administered in the form of a wash liquid or incorporated in a gel. Chronic wounds often carry infection, and the use of microspheres with drug release triggered by the bacterial infection is therefore of interest. A lipophilic drug or a model of the drug was dissolved in an oil and the oil phase was dispersed into an o/w emulsion. A nanofilm shell was then assembled around the oil droplets with the layer-by-layer technique using the two biodegradable polypeptides anionic poly-L-glutamic acid (PLGA) and cationic poly-L-lysine (PLL). Since S. aureus exudes proteases such as glutamyl endopeptidase (V8) during colonization and infection, its substrate specificity was key when assembling the nanofilm. Since V8 is known to be substrate specific to the Glu-X bond, PLGA was chosen as the terminating layer of the nanofilm. Crosslinking the nanofilm after assembly lead to increased stability of the microspheres. It was shown that in a non-infectious environment, i.e. when a human wound enzyme, HNE (human neutrophile elastase), was present, the microspheres remained intact. The staphylococcal protease V8, on the other hand, readily catalyzed degradation of the microspheres, thus releasing the drug when triggered by the infectious environment.

  20. Microspheres and their methods of preparation

    DOEpatents

    Bose, Anima B; Yang, Junbing

    2015-03-24

    Carbon microspheres are doped with boron to enhance the electrical and physical properties of the microspheres. The boron-doped carbon microspheres are formed by a CVD process in which a catalyst, carbon source and boron source are evaporated, heated and deposited onto an inert substrate.

  1. Multilayered polymer microspheres by thermal imprinting during microsphere growth.

    PubMed

    Takekoh, Ryu; Li, Wen-Hui; Burke, Nicholas A D; Stöver, Harald D H

    2006-01-11

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

  2. Multilayered polymer microspheres by thermal imprinting during microsphere growth.

    PubMed

    Takekoh, Ryu; Li, Wen-Hui; Burke, Nicholas A D; Stöver, Harald D H

    2006-01-11

    Modulation of the polymerization temperature in precipitation polymerizations was used to form onion-type polymer microspheres consisting of multiple nested layers. Specifically, the copolymerization of chloromethylstyrene and divinylbenzene-55 in acetonitrile, at temperatures ramping between 65 and 75 degrees C, led to monodisperse, cross-linked microspheres of about 10 mum diameter that have radial density profiles closely reflecting the thermal profiles used. This thermal imprinting is attributed to the copolymer formed being close to its theta point during the polymerization. As the microspheres grow by continuously capturing oligomers from solution, the resulting transient surface gel layer expands and contracts with temperature, and thus records the reaction temperature profile in the form of a corresponding density profile, even as it cross-links. PMID:16390152

  3. Optical trapping of coated microspheres.

    PubMed

    Bormuth, Volker; Jannasch, Anita; Ander, Marcel; van Kats, Carlos M; van Blaaderen, Alfons; Howard, Jonathon; Schäffer, Erik

    2008-09-01

    In an optical trap, micron-sized dielectric particles are held by a tightly focused laser beam. The optical force on the particle is composed of an attractive gradient force and a destabilizing scattering force. We hypothesized that using anti-reflection-coated microspheres would reduce scattering and lead to stronger trapping. We found that homogeneous silica and polystyrene microspheres had a sharp maximum trap stiffness at a diameter of around 800 nm--the trapping laser wavelength in water--and that a silica coating on a polystyrene microsphere was a substantial improvement for larger diameters. In addition, we noticed that homogeneous spheres of a correct size demonstrated anti-reflective properties. Our results quantitatively agreed with Mie scattering calculations and serve as a proof of principle. We used a DNA stretching experiment to confirm the large linear range in detection and force of the coated microspheres and performed a high-force motor protein assay. These measurements show that the surfaces of the coated microspheres are compatible with biophysical assays.

  4. Advances in Microsphere Insulation Systems

    NASA Astrophysics Data System (ADS)

    Allen, M. S.; Baumgartner, R. G.; Fesmire, J. E.; Augustynowicz, S. D.

    2004-06-01

    Microsphere insulation, typically consisting of hollow glass bubbles, combines in a single material the desirable properties that other insulations only have individually. The material has high crush strength, low density, is noncombustible, and performs well in soft vacuum. Microspheres provide robust, low-maintenance insulation systems for cryogenic transfer lines and dewars. They also do not suffer from compaction problems typical of perlite that result in the necessity to reinsulate dewars because of degraded thermal performance and potential damage to its support system. Since microspheres are load bearing, autonomous insulation panels enveloped with lightweight vacuum-barrier materials can be created. Comprehensive testing performed at the Cryogenics Test Laboratory located at the NASA Kennedy Space Center demonstrated competitive thermal performance with other bulk materials. Test conditions were representative of actual-use conditions and included cold vacuum pressure ranging from high vacuum to no vacuum and compression loads from 0 to 20 psi. While microspheres have been recognized as a legitimate insulation material for decades, actual implementation has not been pursued. Innovative microsphere insulation system configurations and applications are evaluated.

  5. Polysaccharides as a source of advanced materials: cellulose hollow microspheres for drug delivery in cancer therapy.

    PubMed

    Metaxa, Aikaterini-Foteini; Efthimiadou, Eleni K; Boukos, Nikos; Kordas, George

    2012-10-15

    Biocompatible hollow poly(methyl acrylic acid-co-N-isopropylacrylamide-co-ethyleneglycol dimethacrylate)@cellulose succinate (P(MAA-co-NIPAAM-co-EGDMA)@CS) microspheres have been synthesized by employing uniform silica-MPS microspheres as template. Silica spheres were synthesized via Stöber method involving tetraethyl orthosilicate. The surface of resulting silica Stöber microspheres was modified using 3-methacryloxypropyltrimethoxysilane (MPS), a polymerizable silane coupling agent. The above reagent introduces carbon-carbon double bonds on microspheres' surface. This strategy uses the copolymerization of the following monomers, methacrylic acid (MAA), N-isopropyl acrylamide (NIPAAM) and the ethyleneglycol dimethacrylate (EGDMA), which was used as cross-linker, aiming at fabricating the first shell. Distillation precipitation polymerization method was carried out with 2,2-azobis(2-methylpropionitrile) as initiator in acetonitrile aiming at coating the inorganic microspheres with organic shell of the above-mentioned copolymer. In continuation, cellulose succinate and cellulose powder was absorbed through electrostatic interactions onto microspheres' surface and the isolated product was cross-linked through esteric bonds formation. The cellulose succinate hollow microspheres were obtained after the silica core removal. The resulting spheres were characterized by Fourier transform infrared spectroscopy and observed by scanning and transmission electron microscopy. Dynamic light scattering was used to study the hydrodynamic diameter of the synthesized microspheres. The anticancer drug daunorubicin was loaded in the spheres, and its release behavior was evaluated at acidic and slightly basic pH conditions, aiming at evaluating its behavior at the healthy and pathogenic tissues.

  6. Preparation, characterization, and in vitro testing of poly(lactide-co-glycolide) and dextran magnetic microspheres for in vivo applications

    NASA Astrophysics Data System (ADS)

    Leamy, Patrick J.

    Many research groups are investigating degradable magnetic particles for magnetic resonance imaging (MRI) contrast agents and as carriers for magnetic drug guidance. These particles are composite materials with a degradable polymer matrix and iron oxide nanoparticles for magnetic properties. The degradable polymer matrix acts to provide colloidal stability and, for drug delivery applications, provides a reservoir for the storage and release of drugs. Natural polymers, like albumin and dextran, which degrade by the action of enzymes; have been used for the polymer matrix. Iron oxide nanoparticles are used for magnetic properties since they can be digested in vivo and have low toxicities. Polylactic acid (PLA) and its copolymers with polyglycolic acid (PLGA) are versatile polymers that degrade by simple hydrolysis without the aid of enzymes. Microspheres are easily formed using the solvent extraction/evaporation method and a wide range of drugs can be encapsulated in them. Magnetic PLGA microspheres suitable for applications were synthesized for the first time in this dissertation. This was accomplished by coating iron oxide nanoparticles with oleic acid to make them dispersible in the organic solvents used in the extraction/evaporation microsphere preparation method. In addition to the magnetic PLGA microspheres, a novel all-aqueous method for preparing crosslinked dextran magnetic microspheres was developed in this dissertation. This method uses free radical polymerization for crosslinking and does not require the use of flammable and harmful solvents. For efficient MRI contrast and magnetic drug guidance, maximized iron oxide content of microspheres is desirable. The two different microsphere preparation methods were optimized for iron oxide content. The effect of iron oxide content on microsphere size and morphology was studied. In addition, an in vitro circulation model was used to evaluate the ability of magnetic microspheres to be guided at physiologic blood

  7. Demonstration of sub-femtomole sensitivity for small molecules with microsphere ring resonator sensors

    NASA Astrophysics Data System (ADS)

    White, Ian M.; Oveys, Hesam; Fan, Xudong

    2006-02-01

    Optical microsphere resonators can function as highly sensitive bio/chemical sensors due to the large Q-factor, which leads to high light-matter interaction. The whispering gallery modes (WGM) arise at the surface of the microsphere, creating a highly enhanced optical field that interacts with matter on or near the microsphere surface. As a result, the spectral position of the WGM is extremely sensitive to refractive index changes near the surface, such as when bio/chemical molecules bind to the sphere. We show the potential feasibility of a microsphere ring resonator as a sensor for small molecules by demonstrating detection of sub-femtomole changes in SiO II molecules at the surface of the microsphere. In this experiment, the silica molecules act as an excellent model for small molecule analytes because of their 60 Dalton molecular weight, and because we know nearly the exact quantity of molecules at the surface, which enables a sensitivity characterization. We measure the spectral shifts in the WGMs when low concentrations of hydrofluoric acid (HF) are added to a solution that is being probed by the microsphere. As the HF molecules break apart the SiO II molecules at the sphere surface, the WGMs shift due to the sub-nano-scale decrease in the size of the microsphere. These calculations show that the sensitivity of this microsphere resonator is on the order of 500 attomoles. Our results will lead to the utilization of optical microspheres for detection of trace quantities of small molecules for such applications as drug discovery, environmental monitoring, and enzyme detection using peptide cleavage.

  8. Hollow hydroxyapatite microspheres as a device for controlled delivery of proteins

    PubMed Central

    Fu, Hailuo; Day, Delbert E.; Brown, Roger F.

    2011-01-01

    Hollow hydroxyapatite (HA) microspheres were prepared by reacting solid microspheres of Li2O–CaO–B2O3 glass (106–150 μm) in K2HPO4 solution, and evaluated as a controlled delivery device for a model protein, bovine serum albumin (BSA). Reaction of the glass microspheres for 2 days in 0.02 M K2HPO4 solution (pH = 9) at 37°C resulted in the formation of biocompatible HA microspheres with a hollow core diameter equal to 0.6 the external diameter, high surface area (~100 m2/g), and a mesoporous shell wall (pore size ≈13 nm). After loading with a solution of BSA in phosphate-buffered saline (PBS) (5 mg BSA/ml), the release kinetics of BSA from the HA microspheres into a PBS medium were measured using a micro bicinchoninic acid (BCA) protein assay. Release of BSA initially increased linearly with time, but almost ceased after 24–48 h. Modification of the BSA release kinetics was achieved by modifying the microstructure of the as-prepared HA microspheres using a controlled heat treatment (1–24 h at 600–900°C). Sustained release of BSA was achieved over 7–14 days from HA microspheres heated for 5 h at 600°C. The amount of BSA released at a given time was dependent on the concentration of BSA initially loaded into the HA microspheres. These hollow HA microspheres could provide a novel inorganic device for controlled local delivery of proteins and drugs. PMID:21290170

  9. Polarization Dependent Whispering Gallery Modes in Microspheres

    NASA Technical Reports Server (NTRS)

    Adamovsky, Grigory (Inventor); Wrbanek, Susan Y. (Inventor)

    2016-01-01

    A tunable resonant system is provided and includes a microsphere that receives an incident portion of a light beam generated via a light source, the light beam having a fundamental mode, a waveguide medium that transmits the light beam from the light source to the microsphere, and a polarizer disposed in a path of the waveguide between the light source and the microsphere. The incident portion of the light beam creates a fundamental resonance inside the microsphere. A change in a normalized frequency of the wavelength creates a secondary mode in the waveguide and the secondary mode creates a secondary resonance inside the microsphere.

  10. Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.

    PubMed

    Efthimiadou, Eleni K; Tapeinos, Christos; Chatzipavlidis, Alexandros; Boukos, Nikos; Fragogeorgi, Eirini; Palamaris, Lazaros; Loudos, George; Kordas, George

    2014-01-30

    This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging.

  11. Improving Protein Stability and Controlling Protein Release by Adding Poly (Cyclohexane-1, 4-Diyl Acetone Dimethylene Ketal) to PLGA Microspheres.

    PubMed

    Wang, Chenhui; Yu, Changhui; Yu, Kongtong; Teng, Lesheng; Liu, Jiaxin; Wang, Xuesong; Sun, Fengying; Li, Youxin

    2015-01-01

    The use of biodegradable polymers such as PLGA to encapsulate therapeutic proteins for their controlled release has received tremendous interest. However, an acidic environment caused by PLGA degradation productions leads to protein incomplete release and chemical degradation. The aim of this study was to develop novel PCADK/PLGA microspheres to improve protein stability and release behavior. Bovine serum albumin (BSA) incubated in PCADK and PLGA degradation products was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Blended microspheres of PCADK/PLGA were prepared in different ratios and the release behaviors of the microspheres and the protein stability were then measured. The degradation properties of the microspheres and the pH inside the microspheres were systematically investigated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) to examine the mechanism of autocatalytic degradation and protein stability. BSA was more stable in the presence of PCADK monomers than it was in the presence of PLGA monomers, revealing that PCADK is highly compatible with this protein. PCADK/PLGA microspheres were successfully prepared, and 2/8 was determined to be the optimal ratio. Further, 43% of the BSA formed water-insoluble aggregates in the presence of PCADK/PLGA microspheres, compared with 57% for the PLGA microspheres, demonstrating that the BSA encapsulated in PCADK/PLGA blended microspheres was more stable than in PLGA microspheres. The PCADK/PLGA blended microspheres improved protein stability and release behavior, providing a promising protein drug delivery system.

  12. Tuning the degradation rate of calcium phosphate cements by incorporating mixtures of polylactic-co-glycolic acid microspheres and glucono-delta-lactone microparticles.

    PubMed

    Sariibrahimoglu, Kemal; An, Jie; van Oirschot, Bart A J A; Nijhuis, Arnold W G; Eman, Rhandy M; Alblas, Jacqueline; Wolke, Joop G C; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander C G; Jansen, John A

    2014-11-01

    Calcium phosphate cements (CPCs) are frequently used as synthetic bone graft materials in view of their excellent osteocompatibility and clinical handling behavior. Hydroxyapatite-forming CPCs, however, degrade at very low rates, thereby limiting complete bone regeneration. The current study has investigated whether degradation of apatite-forming cements can be tuned by incorporating acid-producing slow-resorbing poly(D,L-lactic-co-glycolic) acid (PLGA) porogens, fast-resorbing glucono-delta-lactone (GDL) porogens, or mixtures thereof. The physicochemical, mechanical, and degradation characteristics of these CPC formulations were systematically analyzed upon soaking in phosphate-buffered saline (PBS). In parallel, various CPC formulations were implanted intramuscularly and orthotopically on top of the transverse process of goats followed by analysis of the soft tissue response and bone ingrowth after 12 weeks. In vitro degradation of GDL was almost completed after 2 weeks, as evidenced by characterization of the release of gluconic acid, while PLGA-containing CPCs released glycolic acid throughout the entire study (12 weeks), resulting in a decrease in compression strength of CPC. Extensive in vitro degradation of the CPC matrix was observed upon simultaneous incorporation of 30% PLGA-10% GDL. Histomorphometrical evaluation of the intramuscularly implanted samples revealed that all CPCs exhibited degradation, accompanied by an increase in capsule thickness. In the in vivo goat transverse process model, incorporation of 43% PLGA, 30% PLGA-5% GDL, and 30% PLGA-10% GDL in CPC significantly increased bone formation and resulted in higher bone height compared with both 10% GDL and 20% GDL-containing CPC samples.

  13. pH-responsive composite microspheres based on magnetic mesoporous silica nanoparticle for drug delivery.

    PubMed

    Wen, Hao; Guo, Jia; Chang, Baisong; Yang, Wuli

    2013-05-01

    pH-responsive composite microspheres, consisting of a core of Fe₃O₄ nanoparticle, a sandwiched layer of mesoporous silica and a shell of crosslinked poly (methacrylic acid) (PMAA), were successfully synthesized via distillation precipitation polymerization. The pKa of the composite microsphere increased with the increase in the crosslinking density. Doxorubicin hydrochloride (DOX) was applied as a model drug, and the behavior of drug storage/release was investigated. The cumulative release of DOX-loaded composite microsphere in vitro showed that the drug release rate was much faster below its pKa than that of above its pKa. Because pH of most tumor tissues was lower than that of normal tissues, the pH-responsive composite microspheres are promising drug delivery system especially for cancer therapy.

  14. Melanoidin and aldocyanoin microspheres - Implications for chemical evolution and early Precambrian micropaleontology

    NASA Technical Reports Server (NTRS)

    Kenyon, D. H.; Nissenbaum, A.

    1976-01-01

    Two new classes of organic microspheres are described. One of them (melanoidin) is synthesized from amino acids and sugars in heated aqueous solutions. The other (aldocyanoin) is formed in aqueous solutions of ammonium cyanide and formaldehyde at room temperature. The general properties of these microspheres, including conditions of synthesis, size and shape, mechanical and pH stability, and solubility, are compared with corresponding properties of other protocell model systems. It is concluded that melanoidin and aldocyanoin microspheres are plausible candidates for precellular units in the primitive hydrosphere. Since the bulk of the organic carbon in early Precambrian sediments is insoluble kerogen-melanoidin, it is suggested that some Precambrian microfossils may be abiotic melanoidin microspheres.

  15. Preparation of porous microsphere-scaffolds by electrohydrodynamic forming and thermally induced phase separation.

    PubMed

    Ghanbar, Hanif; Luo, C J; Bakhshi, Poonam; Day, Richard; Edirisinghe, Mohan

    2013-07-01

    The availability of forming technologies able to mass produce porous polymeric microspheres with diameters ranging from 150 to 300 μm is significant for some biomedical applications where tissue augmentation is required. Moreover, appropriate assembly of microspheres into scaffolds is an important challenge to enable direct usage of the as-formed structures in treatments. This work reports the production of poly (glycolic-co-lactic acid) and poly (ε-caprolactone) microspheres under ambient conditions using one-step electrohydrodynamic jetting (traditionally known as atomisation) and thermally induced phase separation (TIPS). To ensure robust production for practical uses, this work presents 12 comprehensive parametric mode mappings of the diameter distribution profiles of the microspheres obtained over a broad range of key processing parameters and correlating of this with the material parameters of 5 different polymer solutions of various concentrations. Poly (glycolic-co-lactic acid) (PLGA) in Dimethyl carbonate (DMC), a low toxicity solvent with moderate conductivity and low dielectric constant, generated microspheres within the targeted diameter range of 150-300 μm. The fabrication of the microspheres suitable for formation of the scaffold structure is achieved by changing the collection method from distilled water to liquid nitrogen and lyophilisation in a freeze dryer. PMID:23623059

  16. Biodegradable microsphere-mediated cell perforation in microfluidic channel using femtosecond laser

    NASA Astrophysics Data System (ADS)

    Ishii, Atsuhiro; Ariyasu, Kazumasa; Mitsuhashi, Tatsuki; Heinemann, Dag; Heisterkamp, Alexander; Terakawa, Mitsuhiro

    2016-05-01

    The use of small particles has expanded the capability of ultrashort pulsed laser optoinjection technology toward simultaneous treatment of multiple cells. The microfluidic platform is one of the attractive systems that has obtained synergy with laser-based technology for cell manipulation, including optoinjection. We have demonstrated the delivery of molecules into suspended-flowing cells in a microfluidic channel by using biodegradable polymer microspheres and a near-infrared femtosecond laser pulse. The use of polylactic-co-glycolic acid microspheres realized not only a higher optoinjection ratio compared to that with polylactic acid microspheres but also avoids optical damage to the microfluidic chip, which is attributable to its higher optical intensity enhancement at the localized spot under a microsphere. Interestingly, optoinjection ratios to nucleus showed a difference for adhered cells and suspended cells. The use of biodegradable polymer microspheres provides high throughput optoinjection; i.e., multiple cells can be treated in a short time, which is promising for various applications in cell analysis, drug delivery, and ex vivo gene transfection to bone marrow cells and stem cells without concerns about residual microspheres.

  17. Poly(ethylene glycol) methacrylate hydrolyzable microspheres for transient vascular embolization.

    PubMed

    Louguet, Stéphanie; Verret, Valentin; Bédouet, Laurent; Servais, Emeline; Pascale, Florentina; Wassef, Michel; Labarre, Denis; Laurent, Alexandre; Moine, Laurence

    2014-03-01

    Poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres. All synthesized microspheres were spherical in shape, calibrated in the 300-500 μm range, swelled in phosphate-buffered saline (PBS) and easily injectable through a microcatheter. Hydrolytic degradation experiments performed in PBS at 37 °C showed that all of the formulations tested were totally degraded in less than 2 days. The resulting degradation products were a mixture of low-molecular-weight compounds (PEG, lactic and glycolic acids) and water-soluble polymethacrylate chains having molecular weights below the threshold for renal filtration of 50 kg mol(-1) for the microspheres containing MDO. Both the microspheres and the degradation products were determined to exhibit minimal cytotoxicity against L929 fibroblasts. Additionally, in vivo implantation in a subcutaneous rabbit model supported the in vitro results of a rapid degradation rate of microspheres and provided only a mild and transient inflammatory reaction comparable to that of the control group. PMID:24321348

  18. Mechanism of drug release from double-walled PDLLA(PLGA) microspheres

    PubMed Central

    Xu, Qingxing; Chin, Shi En; Wang, Chi-Hwa; Pack, Daniel W.

    2013-01-01

    The drug release and degradation behavior of two double-walled microsphere formulations consisting of a doxorubicin loaded poly(D,L-lactic-co-glycolic acid) (PLGA) core (~46 kDa) surrounded by a poly(D,L-lactic acid) (PDLLA) shell layer (~55 and 116 kDa) were examined. It was postulated that different molecular weights of the shell layer could modulate the erosion of the outer coating and limit the occurrence of water penetration into the inner drug-loaded core on various time scales, and therefore control the drug release from the microspheres. For both microsphere formulations, the drug release profiles were observed to be similar. The degradation of the microspheres was monitored for a period of about nine weeks and analyzed using scanning electron microscopy, laser scanning confocal microscopy, and gel permeation chromatography. Interestingly, both microsphere formulations exhibited occurrence of bulk erosion of PDLLA on a similar time scale despite different PDLLA molecular weights forming the shell layer. The shell layer of the double-walled microspheres served as an effective diffusion barrier during the initial lag phase period and controlled the release rate of the hydrophilic drug independent of the molecular weight of the shell layer. PMID:23453059

  19. Microstructured microspheres of hydroxyapatite bioceramic.

    PubMed

    Sunny, M C; Ramesh, P; Varma, H K

    2002-07-01

    Hydroxyapatite (HAP) particles having spherical geometry and 125-1000 microm in size range were prepared using a solid-in-water-in-oil (S/W/O) emulsion, cross-linking technique. An aqueous solution of chitosan containing different loading of HAP was dispersed as droplet in liquid paraffin using a stabilizing agent. Cross-linking of chitosan was induced by adding appropriate amount of glutaraldehyde saturated toluene. Chitosan microspheres containing HAP were sintered at 1150 degrees C to obtain pure HAP microspheres. The spheres thus produced were examined by scanning electron microscopy. The percentage yield and size distributions of the spheres were also determined.

  20. Production of monodisperse, polymeric microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Rhim, Won-Kyu (Inventor); Hyson, Michael T. (Inventor); Chang, Manchium (Inventor)

    1990-01-01

    Very small, individual polymeric microspheres with very precise size and a wide variation in monomer type and properties are produced by deploying a precisely formed liquid monomer droplet, suitably an acrylic compound such as hydroxyethyl methacrylate into a containerless environment. The droplet which assumes a spheroid shape is subjected to polymerizing radiation such as ultraviolet or gamma radiation as it travels through the environment. Polymeric microspheres having precise diameters varying no more than plus or minus 5 percent from an average size are recovered. Many types of fillers including magnetic fillers may be dispersed in the liquid droplet.

  1. PREPARATION AND CHARACTERIZATION OF POROUS WALLED HOLLOW GLASS MICROSPHERES

    SciTech Connect

    Raszewski, F; Erich Hansen, E; Ray Schumacher, R; David Peeler, D

    2008-04-21

    Porous-walled hollow glass microspheres (PWHGMs) of a modified alkali borosilicate composition have been successfully fabricated by combining the technology of producing hollow glass microspheres (HGMs) with the knowledge associated with porous glasses. HGMs are first formed by a powder glass--flame process, which are then transformed to PWHGMs by heat treatment and subsequent treatment in acid. Pore diameter and pore volume are most influenced by heat treatment temperature. Pore diameter is increased by a factor of 10 when samples are heat treated prior to acid leaching; 100 {angstrom} in non-heat treated samples to 1000 {angstrom} in samples heat treated at 600 C for 8 hours. As heat treatment time is increased from 8 hours to 24 hours there is a slight shift increase in pore diameter and little or no change in pore volume.

  2. Gamma Irradiation of Active Self-healing PLGA Microspheres for Efficient Aqueous Encapsulation of Vaccine Antigens

    PubMed Central

    Desai, Kashappa-Goud H.; Kadous, Samer; Schwendeman, Steven P.

    2013-01-01

    Purpose To investigate the effect of γ-irradiation of poly(lactic-co-glycolic acid) (PLGA)/Al(OH)3/0 or 5 wt% diethyl phthalate (DEP) microspheres for active self-healing encapsulation of vaccine antigens. Methods Microspheres were irradiated with 60Co at 2.5 and 1.8 MRad and 0.37 and 0.20 MRad/h. Encapsulation of tetanus toxoid (TT) was achieved by mixing Al(OH)3-PLGA microspheres with TT solution at 10-38°C. Electron paramagnetic resonance (EPR) spectroscopy was used to examine free radical formation. Glass transition temperature (Tg) and molecular weight of PLGA was measured by differential scanning calorimetry and gel permeation chromatography, respectively. Loading and release of TT were examined by modified Bradford, amino acid analysis, and ELISA assays. Results EPR spectroscopy results indicated absence of free radicals in PLGA microspheres after γ-irradiation. Antigen-sorbing capacity, encapsulation efficiency, and Tg of the polymer were also not adversely affected. When DEP-loaded microspheres were irradiated at 0.2 MRad/h, some PLGA pores healed during irradiation and PLGA healing during encapsulation was suppressed. The molecular weight of PLGA was slightly reduced when DEP-loaded microspheres were irradiated at the same dose rate. These trends were not observed at 0.37 MRad/h. Gamma irradiation slightly increased TT initial burst release. Apart from the slightly higher polymer molecular weight decline caused by higher irradiation dose in case of DEP-loaded microspheres, the small increase in total irradiation dose from 1.8 to 2.5 MRad had insignificant effect on the polymer and microspheres properties analyzed. Conclusion Gamma irradiation is a plausible approach to provide a terminally sterilized, self-healing encapsulation PLGA excipient for vaccine delivery. PMID:23515830

  3. Conferring Natural-Derived Porous Microspheres with Surface Multifunctionality through Facile Coordination-Enabled Self-Assembly Process.

    PubMed

    Han, Pingping; Shi, Jiafu; Nie, Teng; Zhang, Shaohua; Wang, Xueyan; Yang, Pengfei; Wu, Hong; Jiang, Zhongyi

    2016-03-01

    In this study, multifunctional chitin microspheres are synthesized and utilized as a platform for multiple potential applications in enzyme immobilization, catalytic reduction and adsorption. Porous chitin microspheres with an average diameter of 111.5 μm and a porous architecture are fabricated through a thermally induced phase separation method. Then, the porous chitin microspheres are conferred with surface multifunctionality through facile coordination-enabled self-assembly of tannic acid (TA) and titanium (Ti(IV)) bis(ammonium lactate)dihydroxide (Ti-BALDH). The multipoint hydrogen bonds between TA and chitin microspheres confer the TA-Ti(IV) coating with high adhesion capability to adhere firmly to the surface of the chitin microspheres. In view of the biocompatibility, porosity and surface activity, the multifunctional chitin microspheres are used as carriers for enzyme immobilization. The enzyme-conjugated multifunctional porous microspheres exhibit high catalytic performance (102.8 U·mg(-1) yeast alcohol dehydrogenase). Besides, the multifunctional chitin microspheres also find potential applications in the catalytic reduction (e.g., reduction of silver ions to silver nanoparticles) and efficient adsorption of heavy metal ions (e.g., Pb(2+)) taking advantages of their porosity, reducing capability and chelation property.

  4. Development of Risperidone PLGA Microspheres

    PubMed Central

    D'Souza, Susan; Faraj, Jabar A.; Giovagnoli, Stefano; DeLuca, Patrick P.

    2014-01-01

    The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug. PMID:24616812

  5. Microspheres and nanoparticles from ultrasound

    NASA Astrophysics Data System (ADS)

    Suh, Won Hyuk

    Improved preparations of various examples of monodispersed, porous, hollow, and core-shell metal and semiconductor nanoparticles or nanowires have been developed. Now titania microspheres and nanoparticles and silica microspheres can be synthesized using an inexpensive high frequency (1.7 MHz) ultrasonic generator (household humidifier; ultrasonic spray pyrolysis; USP). Morphology and pore size of titania microspheres were controlled by the silica to Ti(IV) ratio and silica particle size. Fine tuning the precursor ratio affords sub-50 nm titania nanoparticles as well. In terms of silica microspheres, morphology was controlled by the silica to organic monomer ratio. In liquids irradiated with high intensity ultrasound (20 kHz; HIUS), acoustic cavitation produces high energy chemistry through intense local heating inside the gas phase of collapsing bubbles in the liquid. HIUS and USP confine the chemical reactions to isolated sub-micron reaction zones, but sonochemistry does so in a heated gas phase within a liquid, while USP uses a hot liquid droplet carried by a gas flow. Thus, USP can be viewed as a method of phase-separated synthesis using submicron-sized droplets as isolated chemical reactors for nanomaterial synthesis. While USP has been used to create both titania and silica spheres separately, there are no prior reports of titania-silica composites. Such nanocomposites of metal oxides have been produced, and by further manipulation, various porous structures with fascinating morphologies were generated. Briefly, a precursor solution was nebulized using a commercially available household ultrasonic humidifier (1.7 MHz ultrasound generator), and the resulting mist was carried in a gas stream of air through a quartz glass tube in a hot furnace. After exiting the hot zone, these microspheres are porous or hollow and in certain cases magnetically responsive. In the case of titania microspheres, they are rapidly taken up into the cytoplasm of mammalian cells and

  6. Rapid magnetic-mediated solid-phase extraction and pre-concentration of selected endocrine disrupting chemicals in natural waters by poly(divinylbenzene-co-methacrylic acid) coated Fe3O4 core-shell magnetite microspheres for their liquid chromatography-tandem mass spectrometry determination.

    PubMed

    Li, Qingling; Lam, Michael H W; Wu, Rudolf S S; Jiang, Biwang

    2010-02-19

    A new Fe(3)O(4)/poly(divinylbenzene-co-methacrylic acid) core-shell magnetite microspheric material have been successfully developed as magnetic-mediated solid-phase extraction micro-particle sorbent in dispersion mode (MM-SPE-MP) for the determination of selected estrogenic endocrine disrupting chemicals (EDCs), namely: estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethynylestradiol (EE2) and bisphenol-A (BPA), in natural water, via quantification by HPLC tandem mass spectrometry. The magnetite Fe(3)O(4) core of this MM-SPE-MP sorbent was fabricated by a solvothermal approach and the thin layer of amphipolar poly(divinylbenzene-co-methacrylic acid) (pDVB-MAA) coating was established via suspension polymerization. The resultant core-shell MM-SPE-MP sorbent material was characterized by electron microscopy, X-ray diffraction and Fourier-transformed infrared spectroscopy. Particle size distribution of the core-shell microspheres was within the range 300-700 nm in diameter and the thickness of the pDVB-MAA coating was ca. 10nm. This magnetite microspheric material can be easily dispersed in aqueous samples and retrieved by the application of external magnetic field via a small piece of permanent magnet. The MM-SPE-MP process for the selected estrogenic EDCs involved the dispersion of the core-shell microspheric sorbent in water samples with sonication, followed by magnetic aided retrieval of the sorbent and solvent (methanol) desorption of extracted EDCs for LC-MS/MS analysis. Partition equilibrium for all the selected EDCs onto this MM-SPE-MP sorbent was achieved within 15 min. Recoveries of the EDCs were in ranges of 56-111%. Analytes with smaller K(OW) value showed relatively lower recovery (and relatively longer equilibration time for partitioning). Method detection limits achieved were found to be 1-36 pg ml(-1) (n=3), while the repeatability was 6-34% (p<0.05, n=3). This work demonstrates the usefulness of MM-SPE-MP in the rapid and highly sensitive

  7. Comparing microspheres with different internal phase of polyelectrolyte as local drug delivery system for bone tuberculosis therapy.

    PubMed

    Wu, Gang; Chen, Long; Li, Hong; Deng, Chun-Ling; Chen, Xiao-Feng

    2014-01-01

    We use hydrophobic poly(lactic-co-glycolic) acid (PLGA) to encapsulate hydrophilic ofloxacin to form drug loading microspheres. Hyaluronic acid (HA) and polylysine (Pls) were used as internal phase additives to see their influences on the drug loading and releasing. Double emulsion (water-in-oil-in-water) solvent extraction/evaporation method was used for the purpose. Particle size analysis display that the polyelectrolytes have low impact on the microsphere average size and distribution. Scanning electron microscope (SEM) pictures show the wrinkled surface resulted by the internal microcavity of the microspheres. Microspheres with HA inside have higher drug loading amounts than microspheres with Pls inside. The loading drug amounts of the microspheres increase with the HA amounts inside, while decreasing with the Pls amounts inside. All the polyelectrolytes adding groups have burst release observed in experiments. The microspheres with Pls internal phase have faster release rate than the HA groups. Among the same polyelectrolyte internal phase groups, the release rate increases with the amounts increasing when Pls is inside, while it decreases with the amounts increasing when HA is inside.

  8. Magnetic nanoparticles-loaded PLA/PEG microspheres as drug carriers.

    PubMed

    Frounchi, Masoud; Shamshiri, Soodeh

    2015-05-01

    Surface-modified magnetite (Fe3 O4 ) nanoparticles with an average size of 22 nm were prepared. The nanoparticles had a saturation magnetization of 50.7 emu g(-1) . Then magnetite and drug-loaded microspheres of poly (lactic acid)/poly (ethylene glycol) were prepared at various compositions. The microspheres were spherical in shape and had smooth surface. The diameter size of the microspheres ranged between about 0.2 and 4 μm. Doxorubicin hydrochloride for cancer treatment was the drug that loaded into the microspheres. The prepared microspheres were characterized by FTIR, XRD, VSM, SEM and drug-release measurements. It was found that the drug cumulative release percentage was proportional to (time) (n) where 0.61 < n < 0.75 depending on PEG and Fe3 O4 contents. The drug release was controlled through a combination of diffusion and PLA hydrolysis and obeyed a non-fickian mechanism. The drug release was facilitated by presence of poly (ethylene glycol) as PLA plasticizer and was higher under applied external magnetic field. The obtained magnetic microspheres could be used as drug carriers for targeted drug delivery purposes. PMID:25203941

  9. Intestine-Specific Delivery of Hydrophobic Bioactives from Oxidized Starch Microspheres with an Enhanced Stability.

    PubMed

    Wang, Shanshan; Chen, Yuying; Liang, Hao; Chen, Yiming; Shi, Mengxuan; Wu, Jiande; Liu, Xianwu; Li, Zuseng; Liu, Bin; Yuan, Qipeng; Li, Yuan

    2015-10-01

    An intestine-specific delivery system for hydrophobic bioactives with improved stability was developed. It consists of oxidized potato starch polymers, where the carboxyl groups were physically cross-linked via ferric ions. The model hydrophobic ingredients (β-carotene) were incorporated inside the starch microspheres via a double-emulsion method. Confocal laser scanning microscopy images showed that β-carotene were distributed homogeneously in the inner oil phase of the starch microspheres. The negative value of the ζ-potential of microspheres increased with increasing pH and decreasing ionic strength. In vitro release experiments showed that the microspheres were stable at acidic stomach conditions (pH < 2), whereas at neutral intestinal conditions (pH 7.0), they rupture to release the loaded β-carotene. The 1,1-diphenyl-2-picrylhydrazyl radical, 2,2-diphenyl-1-(2,4,6-trinitriphenyl), scavenging activity results suggested that microsphere-encapsulated β-carotene had an improved activity after thermal treatment at 80 °C. The storage stability of encapsulated β-carotene at room temperature was also enhanced. The starch microspheres showed potential as intestine-specific carriers with an enhanced stability.

  10. Controlled and Extended Release of a Model Protein from a Microsphere-Hydrogel Drug Delivery System.

    PubMed

    Osswald, Christian R; Kang-Mieler, Jennifer J

    2015-11-01

    In extended ocular drug delivery applications, it is necessary to exert control over the release characteristics of the drug. Design considerations must be made to limit the initial burst (IB) and ensure complete release of drug from the drug delivery system (DDS). In this study, ovalbumin was used as a model protein to explore the effects on release of polymer formulation and fabrication technique in poly(lactic-co-glycolic acid) (PLGA) microspheres. Furthermore, the effect on release of suspending these microspheres in an injectable, thermo-responsive poly(N-isopropylacrylamide)-based hydrogel was determined. To characterize release, ovalbumin was radiolabeled with iodine-125. Regardless of polymer formulation or fabrication technique, pulsatile release was achieved with a second burst occurring after ~70 days for microspheres alone. Suspending PLGA 75:25 microspheres within hydrogel reduced the IB by ~75%, delayed the second burst by 28 days, and extended release out to ~200 days with steadier, consistent release throughout compared to microspheres alone. The combined microsphere-hydrogel DDS remains injectable through small-gauge needles and may have many applications, namely ocular drug delivery to the posterior segment.

  11. Magnetic nanoparticles-loaded PLA/PEG microspheres as drug carriers.

    PubMed

    Frounchi, Masoud; Shamshiri, Soodeh

    2015-05-01

    Surface-modified magnetite (Fe3 O4 ) nanoparticles with an average size of 22 nm were prepared. The nanoparticles had a saturation magnetization of 50.7 emu g(-1) . Then magnetite and drug-loaded microspheres of poly (lactic acid)/poly (ethylene glycol) were prepared at various compositions. The microspheres were spherical in shape and had smooth surface. The diameter size of the microspheres ranged between about 0.2 and 4 μm. Doxorubicin hydrochloride for cancer treatment was the drug that loaded into the microspheres. The prepared microspheres were characterized by FTIR, XRD, VSM, SEM and drug-release measurements. It was found that the drug cumulative release percentage was proportional to (time) (n) where 0.61 < n < 0.75 depending on PEG and Fe3 O4 contents. The drug release was controlled through a combination of diffusion and PLA hydrolysis and obeyed a non-fickian mechanism. The drug release was facilitated by presence of poly (ethylene glycol) as PLA plasticizer and was higher under applied external magnetic field. The obtained magnetic microspheres could be used as drug carriers for targeted drug delivery purposes.

  12. Electrospray synthesis and properties of hierarchically structured PLGA TIPS microspheres for use as controlled release technologies.

    PubMed

    Malik, Salman A; Ng, Wing H; Bowen, James; Tang, Justin; Gomez, Alessandro; Kenyon, Anthony J; Day, Richard M

    2016-04-01

    Microsphere-based controlled release technologies have been utilized for the long-term delivery of proteins, peptides and antibiotics, although their synthesis poses substantial challenges owing to formulation complexities, lack of scalability, and cost. To address these shortcomings, we used the electrospray process as a reproducible, synthesis technique to manufacture highly porous (>94%) microspheres while maintaining control over particle structure and size. Here we report a successful formulation recipe used to generate spherical poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray (ES) coupled with a novel thermally induced phase separation (TIPS) process with a tailored Liquid Nitrogen (LN2) collection scheme. We show how size, shape and porosity of resulting microspheres can be controlled by judiciously varying electrospray processing parameters and we demonstrate examples in which the particle size (and porosity) affect release kinetics. The effect of electrospray treatment on the particles and their physicochemical properties are characterized by scanning electron microscopy, confocal Raman microscopy, thermogravimetric analysis and mercury intrusion porosimetry. The microspheres manufactured here have successfully demonstrated long-term delivery (i.e. 1week) of an active agent, enabling sustained release of a dye with minimal physical degradation and have verified the potential of scalable electrospray technologies for an innovative TIPS-based microsphere production protocol. PMID:26803601

  13. Filling Porous Microspheres With Magnetic Material

    NASA Technical Reports Server (NTRS)

    Chang, Manchium; Colvin, Michael S.

    1990-01-01

    New process produces magnetic microspheres with controllable sizes, compositions, and properties for use in medical diagnostic tests, biological research, and chemical processes. Paramagnetic microspheres also made with process. Porous plastic microspheres prepared by polymerization of monomer in diluent by cross-linking agent. When diluent removed, it leaves tiny pores throughout polymerized spheres. Size and distribution of pores determined by amount and type of diluent and cross-linking agent.

  14. Microsphere coated substrate containing reactive aldehyde groups

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Richard C. K. (Inventor)

    1984-01-01

    A synthetic organic resin is coated with a continuous layer of contiguous, tangential, individual microspheres having a uniform diameter preferably between 100 Angstroms and 2000 Angstroms. The microspheres are an addition polymerized polymer of an unsaturated aldehyde containing 4 to 20 carbon atoms and are covalently bonded to the substrate by means of high energy radiation grafting. The microspheres contain reactive aldehyde groups and can form conjugates with proteins such as enzymes or other aldehyde reactive materials.

  15. Solvothermal synthesis of well-dispersed ZnSe microspheres.

    PubMed

    Ren, Xiaolei; Li, Qiuyu; Xue, Yannan; Zhai, Xuefeng; Yu, Min

    2013-01-01

    Well-defined crystalline ZnSe microspheres have been fabricated successfully via a simple solvothermal route under mild conditions in the presence of ethylenediamine tetraacetic acid disodium salt (Na(2)EDTA) and octadecylamine (ODA). X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectrum (EDS), X-ray photoelectron spectra (XPS), Fourier transform-infrared spectroscopy (FT-IR), and photoluminescence spectra (PL) were used to characterize the phase structures, morphologies, and properties of the products. The result of XRD demonstrated that we obtained ZnSe products crystallized well with a stilleite structure. The influencing elements such as reaction time, sodium hydroxide (NaOH), addition of chelating reagent Na(2)EDTA, and the water/ethanol volume ratio were investigated, and the possible formation mechanism was also proposed. Furthermore, the experimental result indicated that ZnSe microspheres showed blue emission under ultraviolet excitation.

  16. Glass microspheres for medical applications

    NASA Astrophysics Data System (ADS)

    Conzone, Samuel David

    Radioactive dysprosium lithium borate glass microspheres have been developed as biodegradable radiation delivery vehicles for the radiation synovectomy treatment of rheumatoid arthritis. Once injected into a diseased joint, the microspheres deliver a potent dose of radiation to the diseased tissue, while a non-uniform chemical reaction converts the glass into an amorphous, porous, hydrated dysprosium phosphate reaction product. The non-radioactive, lithium-borate component is dissolved from the glass (up to 94% weight loss), while the radioactive 165Dy reacts with phosphate anions in the body fluids, and becomes "chemically" trapped in a solid, dysprosium phosphate reaction product that has the same size as the un-reacted glass microsphere. Ethylene diamine tetraacetate (EDTA) chelation therapy can be used to dissolve the dysprosium phosphate reaction product after the radiation delivery has subsided. The dysprosium phosphate reaction product, which formed in vivo in the joint of a Sprague-Dawley rat, was dissolved by EDTA chelation therapy in <1 week, without causing any detectable joint damage. The combination of dysprosium lithium borate glass microspheres and EDTA chelation therapy provides an unique "tool" for the medical community, which can deliver a large dose (>100 Gy) of localized beta radiation to a treatment site within the body, followed by complete biodegradability. The non-uniform reaction process is a desirable characteristic for a biodegradable radiation delivery vehicle, but it is also a novel material synthesis technique that can convert a glass to a highly porous materials with widely varying chemical composition by simple, low-temperature, glass/solution reaction. The reaction product formed by nonuniform reaction occupies the same volume as the un-reacted glass, and after drying for 1 h at 300°C, has a specific surface area of ≈200 m2/g, a pore size of ≈30 nm, and a nominal crushing strength of ≈10 MPa. Finally, rhenium glass

  17. Coupling system to a microsphere cavity

    NASA Technical Reports Server (NTRS)

    Iltchenko, Vladimir (Inventor); Maleki, Lute (Inventor); Yao, Steve (Inventor); Wu, Chi (Inventor)

    2002-01-01

    A system of coupling optical energy in a waveguide mode, into a resonator that operates in a whispering gallery mode. A first part of the operation uses a fiber in its waveguide mode to couple information into a resonator e.g. a microsphere. The fiber is cleaved at an angle .PHI. which causes total internal reflection within the fiber. The energy in the fiber then forms an evanescent field and a microsphere is placed in the area of the evanescent field. If the microsphere resonance is resonant with energy in the fiber, then the information in the fiber is effectively transferred to the microsphere.

  18. Microsphere-based scaffolds encapsulating chondroitin sulfate or decellularized cartilage.

    PubMed

    Gupta, Vineet; Tenny, Kevin M; Barragan, Marilyn; Berkland, Cory J; Detamore, Michael S

    2016-09-01

    Extracellular matrix materials such as decellularized cartilage (DCC) and chondroitin sulfate (CS) may be attractive chondrogenic materials for cartilage regeneration. The goal of the current study was to investigate the effects of encapsulation of DCC and CS in homogeneous microsphere-based scaffolds, and to test the hypothesis that encapsulation of these extracellular matrix materials would induce chondrogenesis of rat bone marrow stromal cells. Four different types of homogeneous scaffolds were fabricated from microspheres of poly(D,L-lactic-co-glycolic acid): Blank (poly(D,L-lactic-co-glycolic acid) only; negative control), transforming growth factor-β3 encapsulated (positive control), DCC encapsulated, and CS encapsulated. These scaffolds were then seeded with rat bone marrow stromal cells and cultured for 6 weeks. The DCC and CS encapsulation altered the morphological features of the microspheres, resulting in higher porosities in these groups. Moreover, the mechanical properties of the scaffolds were impacted due to differences in the degree of sintering, with the CS group exhibiting the highest compressive modulus. Biochemical evidence suggested a mitogenic effect of DCC and CS encapsulation on rat bone marrow stromal cells with the matrix synthesis boosted primarily by the inherently present extracellular matrix components. An important finding was that the cell seeded CS and DCC groups at week 6 had up to an order of magnitude higher glycosaminoglycan contents than their acellular counterparts. Gene expression results indicated a suppressive effect of DCC and CS encapsulation on rat bone marrow stromal cell chondrogenesis with differences in gene expression patterns existing between the DCC and CS groups. Overall, DCC and CS were easily included in microsphere-based scaffolds; however, there is a requirement to further refine their concentrations to achieve the differentiation profiles we seek in vitro. PMID:27358376

  19. Tabletted microspheres containing Cynara scolymus (var. Spinoso sardo) extract for the preparation of controlled release nutraceutical matrices.

    PubMed

    Gavini, E; Alamanni, M C; Cossu, M; Giunchedi, P

    2005-08-01

    Controlled release dosage forms based on tabletted microspheres containing fresh artichoke Cynara scolymus extract were performed for the oral administration of a nutritional supplement. Microspheres were prepared using a spray-drying technique; lactose or hypromellose have been chosen as excipients. Microspheres were characterized in terms of encapsulated extract content, size and morphology. Qualitative and quantitative composition of the extract before and after the spray process was determined. Compressed matrices (tablets) were prepared by direct compression of the spray-dried microspheres. In vitro release tests of microparticles and tablets prepared were carried out in both acidic and neutral media. Spray-drying is a good method to prepare microspheres containing the artichoke extract. The microspheres encapsulate an amount of extract close to the theoretical value. Particle size analyses indicate that the microparticles have dvs of approximately 6-7 microm. Electronic microscopy observations reveal that particles based on lactose have spherical shape and particles containing hypromellose are almost collapsed. The hydroalcoholic extract is stable to the microsphere production process: its polyphenolic composition (qualitative and quantitative) did not change after spraying. In vitro release studies show that microparticles characterized by a quick polyphenolic release both in acidic and neutral media due to the high water solubility of the carrier lactose. On the contrary, microspheres based hypromellose release only 20% of the loaded extract at pH 1.2 in 2 h and the total amount of polyphenols is released only after about further 6 h at pH 6.8. Matrices prepared tabletting lactose microspheres and hypromellose microparticles in the weight ratio 1:1 show a slow release rate, that lasts approximately 24 h. This one-a-day sustained release formulation containing Cynara scolymus extract could be proposed as a nutraceutical controlled release dosage form for

  20. Compression molding of aerogel microspheres

    DOEpatents

    Pekala, Richard W.; Hrubesh, Lawrence W.

    1998-03-24

    An aerogel composite material produced by compression molding of aerogel microspheres (powders) mixed together with a small percentage of polymer binder to form monolithic shapes in a cost-effective manner. The aerogel composites are formed by mixing aerogel microspheres with a polymer binder, placing the mixture in a mold and heating under pressure, which results in a composite with a density of 50-800 kg/m.sup.3 (0.05-0.80 g/cc). The thermal conductivity of the thus formed aerogel composite is below that of air, but higher than the thermal conductivity of monolithic aerogels. The resulting aerogel composites are attractive for applications such as thermal insulation since fabrication thereof does not require large and expensive processing equipment. In addition to thermal insulation, the aerogel composites may be utilized for filtration, ICF target, double layer capacitors, and capacitive deionization.

  1. Compression molding of aerogel microspheres

    DOEpatents

    Pekala, R.W.; Hrubesh, L.W.

    1998-03-24

    An aerogel composite material produced by compression molding of aerogel microspheres (powders) mixed together with a small percentage of polymer binder to form monolithic shapes in a cost-effective manner is disclosed. The aerogel composites are formed by mixing aerogel microspheres with a polymer binder, placing the mixture in a mold and heating under pressure, which results in a composite with a density of 50--800 kg/m{sup 3} (0.05--0.80 g/cc). The thermal conductivity of the thus formed aerogel composite is below that of air, but higher than the thermal conductivity of monolithic aerogels. The resulting aerogel composites are attractive for applications such as thermal insulation since fabrication thereof does not require large and expensive processing equipment. In addition to thermal insulation, the aerogel composites may be utilized for filtration, ICF target, double layer capacitors, and capacitive deionization. 4 figs.

  2. The controlled release of drugs from emulsified, sol gel processed silica microspheres.

    PubMed

    Radin, Shula; Chen, Tiffany; Ducheyne, Paul

    2009-02-01

    Controlled release silica sol gels are room temperature processed, porous, resorbable materials with generally good compatibility. Many molecules including drugs, proteins and growth factors can be released from sol gels and the quantity and duration of the release can vary widely. Processing parameters render these release properties exquisitely versatile. The synthesis of controlled release sol gels typically includes acid catalyzed hydrolysis to form a sol with the molecules included. This is then followed by casting, aging and drying. Additional steps such as grinding and sieving are required to produce sol gel granules of a desirable size. In this study, we focus on the synthesis of sol gel microspheres by using a novel process with only two steps. The novelty is related to acid-base catalysis of the sol prior to emulsification. Sol gel microspheres containing either vancomycin (antibiotic) or bupivacaine (analgesic) were successfully synthesized using this method. Both drugs showed controlled, load dependent and time dependent release from the microspheres. The in vitro release properties of sol gel microspheres were remarkably different from those of sol gel granules produced by grinding and sieving. In contrast to a fast, short-term release from granules, the release from microspheres was slower and of longer duration. In addition, the degradation rate of microspheres was significantly slower than that of the granules. Using various mathematical models, the data reveal that the release from sol gel powder is governed by two distinct phases of release. In addition, the release from emulsified microspheres is delayed, a finding that can be attributed to differences in surface properties of the particles produced by emulsification and those produced by casting and grinding. The presented results represent an excellent data set for designing and implementing preclinical studies.

  3. Nonaggregating Microspheres Containing Aldehyde Groups

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan

    1989-01-01

    Cobalt gamma irradiation of hydrophilic monomers in presence of acrolein yields exceptionally-stable, nonaggregating microspheres. Mixtures of 2-hydroxyethyl methacrylate (HEMA) and acrolein form homogeneous solutions in distilled water containing 0.4 percent polyethylene oxide (PEO). After deaeration with nitrogen, mixtures irradiated at room temperature with gamma rays from cobalt source; total exposure time 4 hours, at rate of 0.2 milliroentgen per hour. Reaction product centrifuged three times for purification and kept in distilled water.

  4. Microspheres in Plasma Display Panels

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Filling small bubbles of molten glass with gases is just as difficult as it sounds, but the technical staff at NASA is not known to shy away from a difficult task. When Microsphere Systems, Inc. (MSI), of Ypsilanti, Michigan, and Imaging Systems Technology, Inc. (IST), of Toledo, Ohio, were trying to push the limits of plasma displays but were having difficulty with the designs, NASA s Glenn Garrett Morgan Commercialization Initiative (GMCI) assembled key personnel at Glenn Research Center and Ohio State University for a brainstorming session to come up with a solution for the companies. They needed a system that could produce hollow, glass micro-sized spheres (microspheres) that could be filled with a variety of gasses. But the extremely high temperature required to force the micro-sized glass bubbles to form at the tip of a metal nozzle resulted in severe discoloration of the microspheres. After countless experiments on various glass-metal combinations, they had turned to the GMCI for help. NASA experts in advanced metals, ceramics, and glass concluded that a new design approach was necessary. The team determined that what was needed was a phosphate glass composition that would remain transparent, and they went to work on a solution. Six weeks later, using the design tips from the NASA team, Tim Henderson, president of MSI, had designed a new system in which all surfaces in contact with the molten glass would be ceramic instead of metal. Meanwhile, IST was able to complete a Phase I Small Business Innovation Research (SBIR) grant supported by the National Science Foundation (NSF) and supply a potential customer with samples of the microspheres for evaluation as filler materials for high-performance insulations.

  5. Polymethyl methacrylate microspheres in collagen.

    PubMed

    Haneke, Eckart

    2004-12-01

    Artecoll was developed about 20 years ago and underwent a number of production changes until it recently became FDA approved under the new name of Artefill. This product contains 20% polymethyl methacrylate (PMMA) microspheres with a diameter of 30 to 40 microm, which are suspended in a 3.5% atelo-collagen solution. The PMMA microspheres are now purified and no longer have an electrostatic charge, which in part was the cause for the early granulomatous reactions. Further, PMMA has long been known as bone cement and has been used in cosmetic surgery with a very good safety record. PMMA microspheres are biologically inert and nondegradable. The treatment results are therefore permanent and technical errors as well as incorrect injections will last. Due to the early record of granuloma formation, there is still a debate as to whether this product-as well as all other permanent fillers-should be injected for cosmetic reasons or not. With proper indications, excellent injection techniques, and realistic expectations as to what can be expected, this product has now proved to be one of the superior permanent filler substances.

  6. Surface modification of imprinted polymer microspheres with ultrathin hydrophilic shells to improve selective recognition of glutathione in aqueous media.

    PubMed

    Song, Renyuan; Hu, Xiaoling; Guan, Ping; Li, Ji; Du, Chunbao; Qian, Liwei; Wang, Chaoli

    2016-03-01

    A universal, effective approach addressing the classical limitations of hydrophobic molecularly imprinted polymer (MIP) microspheres was described. Two water-compatible MIP microspheres with ultrathin hydrophilic shells were synthesized by controllable surface-graft polymerization using a charged monomer (methacrylic acid) and uncharged monomer (N-isopropylacrylamide) as the hydrophilic functional monomers for the recognition of glutathione in the aqueous medium. The morphological and chemical characteristics of the as-prepared water-compatible MIP microspheres were investigated by scanning electron microscopy, Fourier transform infrared spectroscopy and contact angle measurements. Their selective recognition properties were investigated by static binding tests and compared with those of the ungrafted MIP microspheres. The results of this study showed that the both as-prepared water-compatible MIP microspheres effectively decreased non-specific binding and enhanced the imprinting factor significantly, and the water-compatible MIP microspheres prepared using N-isopropylacrylamide as monomer exhibited a more remarkable recognition property. In addition, the thickness of surface-grafted hydrophilic layer was well controlled by adjusting the irradiation time to obtain the excellent recognition property. Finally, the applicability of the as-prepared water-compatible MIP microspheres as solid-phase extraction materials was investigated by competitive binding tests using a mixture of glutathione and its analogs.

  7. Facile large scale preparation and electromagnetic properties of silica-nickel-carbon composite shelly hollow microspheres.

    PubMed

    An, Zhenguo; Zhang, Jingjie

    2016-02-21

    Silica-nickel-carbon composite microspheres with shelly hollow structures and tunable electromagnetic properties were prepared in large scale through a three-step route. Micron-sized precursor microspheres were prepared firstly by spray drying of water glass. Then a subsequent acid leaching with diluted hydrochloric acid was carried out to eliminate the Na2O in the precursor microspheres to get single shell silica hollow microspheres (SHMs). Afterwards, Ni-C composite shells were assembled on the surface of the previously formed SHMs through a calcination route in an inert atmosphere to form silica-nickel-carbon composite shelly hollow microspheres (CSHMs) through decomposition of the reactants and carbon thermal reduction. By properly tuning the calcination conditions, silica-nickel CSHMs with gradients in composition can also be prepared. The electromagnetic properties of the CSHMs were studied and the results demonstrate that they present ferromagnetic and microwave absorbing properties related to the shell composition. The DSHPs thus obtained may have some promising applications in the fields of low-density magnetic materials and microwave absorbers. This work provides a new strategy to fabricate shelly hollow particles, which can be expected to be extended to the controlled preparation of similar structures with various compositions. PMID:26726765

  8. Optical microdiscus resonators by flattening microspheres

    NASA Astrophysics Data System (ADS)

    Senthil Murugan, Ganapathy; Wilkinson, James S.; Zervas, Michalis N.

    2012-08-01

    A "soften-and-squash" fabrication technique has been demonstrated to controllably deform optical microspheres and form microdiscus resonators with improved surface quality. The characteristic shape of the microdiscus results in superior mode control, and the annealing involved in the fabrication process leads to quality factors (Q) exceeding 105, which is about two orders of magnitude higher than the initial microspheres.

  9. POROUS WALL, HOLLOW GLASS MICROSPHERES

    SciTech Connect

    Sexton, W.

    2012-06-30

    Hollow Glass Microspheres (HGM) is not a new technology. All one has to do is go to the internet and Google{trademark} HGM. Anyone can buy HGM and they have a wide variety of uses. HGM are usually between 1 to 100 microns in diameter, although their size can range from 100 nanometers to 5 millimeters in diameter. HGM are used as lightweight filler in composite materials such as syntactic foam and lightweight concrete. In 1968 a patent was issued to W. Beck of the 3M{trademark} Company for 'Glass Bubbles Prepared by Reheating Solid Glass Particles'. In 1983 P. Howell was issued a patent for 'Glass Bubbles of Increased Collapse Strength' and in 1988 H. Marshall was issued a patent for 'Glass Microbubbles'. Now Google{trademark}, Porous Wall, Hollow Glass Microspheres (PW-HGMs), the key words here are Porous Wall. Almost every article has its beginning with the research done at the Savannah River National Laboratory (SRNL). The Savannah River Site (SRS) where SRNL is located has a long and successful history of working with hydrogen and its isotopes for national security, energy, waste management and environmental remediation applications. This includes more than 30 years of experience developing, processing, and implementing special ceramics, including glasses for a variety of Department of Energy (DOE) missions. In the case of glasses, SRS and SRNL have been involved in both the science and engineering of vitreous or glass based systems. As a part of this glass experience and expertise, SRNL has developed a number of niches in the glass arena, one of which is the development of porous glass systems for a variety of applications. These porous glass systems include sol gel glasses, which include both xerogels and aerogels, as well as phase separated glass compositions, that can be subsequently treated to produce another unique type of porosity within the glass forms. The porous glasses can increase the surface area compared to 'normal glasses of a 1 to 2 order of

  10. Photonic detection and characterization of DNA using sapphire microspheres

    NASA Astrophysics Data System (ADS)

    Murib, Mohammed Sharif; Yeap, Weng-Siang; Martens, Daan; Bienstman, Peter; De Ceuninck, Ward; van Grinsven, Bart; Schöning, Michael J.; Michiels, Luc; Haenen, Ken; Ameloot, Marcel; Serpengüzel, Ali; Wagner, Patrick

    2014-09-01

    A microcavity-based deoxyribonucleic acid (DNA) optical biosensor is demonstrated for the first time using synthetic sapphire for the optical cavity. Transmitted and elastic scattering intensity at 1510 nm are analyzed from a sapphire microsphere (radius 500 μm, refractive index 1.77) on an optical fiber half coupler. The 0.43 nm angular mode spacing of the resonances correlates well with the optical size of the sapphire sphere. Probe DNA consisting of a 36-mer fragment was covalently immobilized on a sapphire microsphere and hybridized with a 29-mer target DNA. Whispering gallery modes (WGMs) were monitored before the sapphire was functionalized with DNA and after it was functionalized with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The shift in WGMs from the surface modification with DNA was measured and correlated well with the estimated thickness of the add-on DNA layer. It is shown that ssDNA is more uniformly oriented on the sapphire surface than dsDNA. In addition, it is shown that functionalization of the sapphire spherical surface with DNA does not affect the quality factor (Q≈104) of the sapphire microspheres. The use of sapphire is especially interesting because this material is chemically resilient, biocompatible, and widely used for medical implants.

  11. Measuring in situ primary and competitive hybridization events on microspheres

    NASA Astrophysics Data System (ADS)

    Milam, Valeria; Hardin, James

    2012-02-01

    Understanding hybridization events at surfaces is crucial for optimizing nucleic acid detection platforms as well as DNA-mediated colloidal assembly. We used flow cytometry to measure time-dependent primary and competitive hybridization events of perfectly matched and mismatched targets on microsphere surfaces. In addition to more conventional sample preparation involving multiple wash and resuspension steps prior to measurement, we sampled the reaction volume directly for in situ measurements to minimize potential dissociation events between weaker partner strands during wash steps. Similar to prior reports for oligonucletide solutions, the nearly identical rates for primary hybridization events on microsphere surfaces were independent of target sequence and reached an equilibrium value within 30 min. The extent of in situ primary hybridization events for immobilized probes, however, deviated from solution model predictions. In situ competitive hybridization events were at least 100-fold slower than primary hybridization events and did not appear to reach equilibrium. The kinetics of competitive hybridization events on microspheres are consistent with predicted effects stemming from toehold effects or base length differences between primary and secondary targets.

  12. Laser-Induced Spallation of Microsphere Monolayers.

    PubMed

    Hiraiwa, Morgan; Stossel, Melicent; Khanolkar, Amey; Wang, Junlan; Boechler, Nicholas

    2016-08-01

    The detachment of a semiordered monolayer of polystyrene microspheres adhered to an aluminum-coated glass substrate is studied using a laser-induced spallation technique. The microsphere-substrate adhesion force is estimated from substrate surface displacement measurements obtained using optical interferometry, and a rigid-body model that accounts for the inertia of the microspheres. The estimated adhesion force is compared with estimates obtained using an adhesive contact model together with interferometric measurements of the out-of-plane microsphere contact resonance, and with estimated work of adhesion values for the polystyrene-aluminum interface. Scanning electron microscope images of detached monolayer regions reveal a unique morphology, namely, partially detached monolayer flakes composed of single hexagonal close packed crystalline domains. This work contributes to the fields of microsphere adhesion and contact dynamics, and demonstrates a unique monolayer delamination morphology. PMID:27409715

  13. Preparation of floating microspheres for fish farming.

    PubMed

    Nepal, Pushp R; Chun, Myung-Kwan; Choi, Hoo-Kyun

    2007-08-16

    The aim of this study was to develop floating microspheres with practical applications to fish farming. Each microsphere with a central hollow cavity was prepared using a solvent diffusion and evaporation method with Eudragit E100. Various manufacturing parameters were investigated by single factor method. The macrolide antibiotic josamycin was selected as a model drug. The loading efficiency of the drug in the microspheres was 64.7%. In the release study, virtually none of the drug was released into the fresh water whereas the entire drug was released from the josamycin-loaded microspheres into the simulated gastric fluid of rainbow trout (pH 2.7). The buoyancy was excellent with approximately 90% of the microspheres still floating after 24h.

  14. Multiplexed Microsphere Suspension Array-Based Immunoassays.

    PubMed

    Lin, Andrew; Salvador, Alexandra; Carter, J Mark

    2015-01-01

    ELISA is an extremely powerful tool to detect analytes because of its sensitivity, selectivity, reproducibility and ease of use. Here we describe sandwich immunoassays performed in suspension on spectrally unique microspheres developed by Luminex. Luminex assays offer the benefit of multiplex analysis of large numbers of analytes in a single reaction. Because the microspheres are spectrally unique, many microspheres, each attached to various antibodies, can be added to a single sample. Luminex instruments can distinguish each microsphere and detect the intensity of a reporter signal for each microsphere. Results are reported in Median Fluorescent Intensities for each analyte. Luminex assays can be used to detect up to 500 analytes in a high-throughput format. Luminex refers to this technology as xMAP(®). Here we describe a routine protocol for a Luminex immunoassay. Other Luminex assays would have to be optimized for specific conditions according to their use. PMID:26160569

  15. Novel core-shell cerium(IV)-immobilized magnetic polymeric microspheres for selective enrichment and rapid separation of phosphopeptides.

    PubMed

    Wang, Zhi-Gang; Cheng, Gong; Liu, Yan-Lin; Zhang, Ji-Lin; Sun, De-Hui; Ni, Jia-Zuan

    2014-03-01

    In this work, novel magnetic polymeric core-shell structured microspheres with immobilized Ce(IV), Fe3O4@SiO2@PVPA-Ce(IV), were designed rationally and synthesized successfully via a facile route for the first time. Magnetic Fe3O4@SiO2 microspheres were first prepared by directly coating a thin layer of silica onto Fe3O4 magnetic particles using a sol-gel method, a poly(vinylphosphonic acid) (PVPA) shell was then coated on the Fe3O4@SiO2 microspheres to form Fe3O4@SiO2@PVPA microspheres through a radical polymerization reaction, and finally Ce(IV) ions were robustly immobilized onto the Fe3O4@SiO2@PVPA microspheres through strong chelation between Ce(IV) ions and phosphate moieties in the PVPA. The applicability of the Fe3O4@SiO2@PVPA-Ce(IV) microspheres for selective enrichment and rapid separation of phosphopeptides from proteolytic digests of standard and real protein samples was investigated. The results demonstrated that the core-shell structured Fe3O4@SiO2@PVPA-Ce(IV) microspheres with abundant Ce(IV) affinity sites and excellent magnetic responsiveness can effectively purify phosphopeptides from complex biosamples for MS detection taking advantage of the rapid magnetic separation and the selective affinity between Ce(IV) ions and phosphate moieties of the phosphopeptides. Furthermore, they can be effectively recycled and show good reusability, and have better performance than commercial TiO2 beads and homemade Fe3O4@PMAA-Ce(IV) microspheres. Thus the Fe3O4@SiO2@PVPA-Ce(IV) microspheres can benefit greatly the mass spectrometric qualitative analysis of phosphopeptides in phosphoproteome research.

  16. Broadband optical absorbance spectroscopy using a whispering gallery mode microsphere resonator

    NASA Astrophysics Data System (ADS)

    Westcott, Sarah L.; Zhang, Jiangquan; Shelton, Robert K.; Bruce, Nellie M. K.; Gupta, Sachin; Keen, Steven L.; Tillman, Jeremy W.; Wald, Lara B.; Strecker, Brian N.; Rosenberger, A. T.; Davidson, Roy R.; Chen, Wei; Donovan, Kevin G.; Hryniewicz, John V.

    2008-03-01

    We demonstrate the ability to excite and monitor many whispering gallery modes (WGMs) of a microsphere resonator simultaneously in order to make broadband optical absorbance measurements. The 340μm diameter microsphere is placed in a microfluidic channel. A hemispherical prism is used for coupling the WGMs into and out of the microsphere. The flat surface of the prism seals the microfluidic channel. The slight nonsphericity in the microsphere results in coupling to precessed modes whose emission is spatially separated from the reflected excitation light. The evanescent fields of the light trapped in WGMs interact with the surrounding environment. The change in transmission observed in the precessed modes is used to determine the absorbance of the surrounding environment. In contrast to our broadband optical absorbance measurements, previous WGM sensors have used only a single narrow mode to measure properties such as refractive index. With the microfluidic cell, we have measured the absorbance of solutions of dyes (lissamine green B, sunset yellow, orange G, and methylene blue), aromatic molecules (benzylamine and benzoic acid), and biological molecules (tryptophan, phenylalanine, tyrosine, and o-phospho-L-tyrosine) at visible and ultraviolet wavelengths. The microsphere surface was reacted with organosilane molecules to attach octadecyl groups, amino groups, and fluorogroups to the surface. Both electrostatic and hydrophobic interactions were observed between the analytes and the microsphere surface, as indicated by changes in the measured effective pathlength with different organosilanes. For a given analyte and coated microsphere, the pathlength measurement was repeatable within a few percent. Methylene blue dye had a very strong interaction with the surface and pathlengths of several centimeters were measured. Choosing an appropriate surface coating to interact with a specific analyte should result in the highest sensitivity detection.

  17. Facile fabrication of biocompatible PLGA drug-carrying microspheres by O/W pickering emulsions.

    PubMed

    Wei, Zengjiang; Wang, Chaoyang; Liu, Hao; Zou, Shengwen; Tong, Zhen

    2012-03-01

    This study is focused on the preparation of Ibuprofen (IBU) loaded micrometer-sized poly(lactic-co-glycolic acid) (PLGA) microspheres and process variables on the size, drug loading and release during preparation of formulation. Silicon dioxide (SiO(2)) nanoparticle-coated PLGA microspheres were fabricated via a combined system of "Pickering-type" emulsion route and solvent volatilization method in the absence of any molecular surfactants. Stable oil-in-water emulsions were prepared using SiO(2) nanoparticles as a particulate emulsifier and a dichloromethane (CH(2)Cl(2)) solution of PLGA as an oil phase. The SiO(2) nanoparticle-coated PLGA microspheres were fabricated by the evaporation of CH(2)Cl(2) in situ, and then bare-PLGA microspheres were prepared by removal of the SiO(2) nanoparticles using HF aqueous solution. The two types of microspheres were characterized in terms of size, component and morphology using scanning electronic microscope (SEM), Fourier-transform infrared, optical microscope, and so on. Moreover, IBU was encapsulated into the hybrid beads by dispersing them in the CH(2)Cl(2) solution of PLGA in the fabrication process. The sustained release could be obtained due to the barrier of the polymeric matrix (PLGA). More over, the release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The combined system of Pickering emulsion and solvent volatilization opens up a new route to fabricate a variety of microspheres. The resulting microspheres may find applications as delivery vehicles for biomolecules, drugs, cosmetics and living cells. PMID:22088755

  18. Facile fabrication of biocompatible PLGA drug-carrying microspheres by O/W pickering emulsions.

    PubMed

    Wei, Zengjiang; Wang, Chaoyang; Liu, Hao; Zou, Shengwen; Tong, Zhen

    2012-03-01

    This study is focused on the preparation of Ibuprofen (IBU) loaded micrometer-sized poly(lactic-co-glycolic acid) (PLGA) microspheres and process variables on the size, drug loading and release during preparation of formulation. Silicon dioxide (SiO(2)) nanoparticle-coated PLGA microspheres were fabricated via a combined system of "Pickering-type" emulsion route and solvent volatilization method in the absence of any molecular surfactants. Stable oil-in-water emulsions were prepared using SiO(2) nanoparticles as a particulate emulsifier and a dichloromethane (CH(2)Cl(2)) solution of PLGA as an oil phase. The SiO(2) nanoparticle-coated PLGA microspheres were fabricated by the evaporation of CH(2)Cl(2) in situ, and then bare-PLGA microspheres were prepared by removal of the SiO(2) nanoparticles using HF aqueous solution. The two types of microspheres were characterized in terms of size, component and morphology using scanning electronic microscope (SEM), Fourier-transform infrared, optical microscope, and so on. Moreover, IBU was encapsulated into the hybrid beads by dispersing them in the CH(2)Cl(2) solution of PLGA in the fabrication process. The sustained release could be obtained due to the barrier of the polymeric matrix (PLGA). More over, the release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The combined system of Pickering emulsion and solvent volatilization opens up a new route to fabricate a variety of microspheres. The resulting microspheres may find applications as delivery vehicles for biomolecules, drugs, cosmetics and living cells.

  19. Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma.

    PubMed

    González-Gómez, Pilar; Crecente-Campo, Jose; Zahonero, Cristina; de la Fuente, Maria; Hernández-Laín, Aurelio; Mira, Helena; Sánchez-Gómez, Pilar; Garcia-Fuentes, Marcos

    2015-05-10

    Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133(+), Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy.

  20. In vitro evaluation and intra-articular administration of biodegradable microspheres containing naproxen sodium.

    PubMed

    Bozdağ, S; Caliş, S; Kaş, H S; Ercan, M T; Peksoy, I; Hincal, A A

    2001-01-01

    The dispersion of non-steroidal antiinflammatory drugs (NSAIDs) into biodegradable polymeric matrices have been accepted as a good approach for obtaining a therapeutic effect in a predetermined period of time meanwhile minimizing the side effects of NSAIDs. In the present study, it was aimed to prepare Naproxen Sodium (NS), (a NSAID) loaded microsphere formulation using natural Bovine Serum Albumin (BSA) and synthetic biodegradable polymers such as poly(lactide-co-glycolic acid) (PLGA) (50:50 MW 34,000 and 88,000 Da) for intra-articular administration, and to study the retention of the drug at the site of injection in the knee joint. NS incorporated microspheres were evaluated in vitro for particle size (the mean particle size; for BSA microspheres, 10.0 +/- 0.3 microm, for PLGA microspheres, 9.0 +/- 0.2 and 5.0 +/- 0.1 microm for MW 34,000 and 88,000 Da, respectively), yield value, drug loading, surface morphology and drug release. For in vivo studies, monoarticular arthritis was induced in the left knee joints of rabbits by using ovalbumin and Freund's Complete Adjuvant as antigen and adjuvant. A certain time (4 days) is allowed for the formation of arthritis in the knee joints, then the NS loaded microspheres were injected directly into the articular cavity. At specific time points, gamma scintigrams were obtained to determine the residence time of the microspheres in knee joints, in order to determine the most suitable formulation. This study indicated that PLGA, a synthetic polymer, is more promising than the natural type BSA microspheres for an effective cure of mono-articular arthritis in rabbits.

  1. Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma.

    PubMed

    González-Gómez, Pilar; Crecente-Campo, Jose; Zahonero, Cristina; de la Fuente, Maria; Hernández-Laín, Aurelio; Mira, Helena; Sánchez-Gómez, Pilar; Garcia-Fuentes, Marcos

    2015-05-10

    Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133(+), Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy. PMID:25860932

  2. Anti-hypertensive effect of oral controlled-release microspheres containing an ACE inhibitor (delapril hydrochloride) in rats.

    PubMed

    Akiyama, Y; Yoshioka, M; Horibe, H; Inada, Y; Hirai, S; Kitamori, N; Toguchi, H

    1994-08-01

    An oral controlled-release drug delivery system based on microspheres of polyglycerol esters of fatty acids (PGEFs), was applied to an anti-hypertensive, delapril hydrochloride. The in-vitro release profile was controlled by selecting a PGEF with an appropriate hydrophilic-lipophilic balance value for the matrix. The microspheres from which 80% of the drug was released in 6 h were orally administered to rats. The plasma concentration of the active metabolite was sustained after administration of the microspheres in comparison with administration of a solution. The in-vivo release profile was in good agreement with the in-vitro release profile. When the microspheres were administered, the pharmacological effect of delapril hydrochloride on the angiotensin I-induced pressor response was also sustained showing consistency with the plasma concentration-time curve.

  3. Hierarchical ZnO-Ag-C composite porous microspheres with superior electrochemical properties as anode materials for lithium ion batteries.

    PubMed

    Xie, Qingshui; Ma, Yating; Zeng, Deqian; Zhang, Xiaoqiang; Wang, Laisen; Yue, Guanghui; Peng, Dong-Liang

    2014-11-26

    Hierarchical ZnO-Ag-C composite porous microspheres are successfully synthesized by calcination of the preproduced zinc-silver citrate porous microspheres in argon. The carbon derives from the in situ carbonization of carboxylic acid groups in zinc-silver citrate during annealing treatment. The average particle size of ZnO-Ag-C composite porous microspheres is approximate 1.5 μm. When adopted as the electrode materials in lithium ion batteries, the obtained composite porous microspheres display high specific capacity, excellent cyclability, and good rate capability. A discharge capacity as high as 729 mA h g(-1) can be retained after 200 cycles at 100 mA g(-1). The excellent electrochemical properties of ZnO-Ag-C are ascribed to its unique hierarchical porous configuration as well as the modification of silver and carbon.

  4. Combination of immune stimulating adjuvants with poly(lactide-co-glycolide) microspheres enhances the immune response of vaccines.

    PubMed

    Salvador, Aiala; Igartua, Manoli; Hernández, Rosa M; Pedraz, José Luis

    2012-01-11

    The development of vaccines that generate mixed humoral and cellular immune responses is a challenge in vaccinology. Poly(lactide-co-glycolide) microspheres are vaccine adjuvants which possess the advantage of allowing the coencapsulation of other adjuvants in addition to the antigen. Thus, we can stimulate the immune system from different ways and resemble the effects of a natural infection. In this study, we have coencapsulated BSA with monophosphoryl lipid A, polyinosinic-polycytidylic acid, α-galactosylceramide and alginate into PLGA microspheres. All the microspheres have developed a higher humoral immune response, in terms of release of total IgG, in comparison to the administration of soluble antigen. In addition, they triggered a more balanced IgG1/IgG2a response. The combination of MPLA and α-galactosylceramide within the microspheres developed the higher cellular response, confirming that combination of adjuvants with different action mechanisms is a good strategy to increase vaccines' immunogenicity.

  5. Synthesis, characterisation and drug release properties of microspheres of polystyrene with aliphatic polyester side-chains.

    PubMed

    Kukut, Manolya; Karal-Yilmaz, Oksan; Yagci, Yusuf

    2014-01-01

    A series of graft copolymers consisting of polystyrene backbone with biocompatible side chains based on (co)polymers of l-lactic acid and glycolic acid were synthesised by combination two controlled polymerisations, namely, nitroxide mediated radical polymerisation (NMRP) and ring opening polymerisation (ROP) with "Click" chemistry. The main goal of this work was to design new biodegradable microspheres using obtained graft copolymers for long-term sustained release of imatinib mesylate (IMM) as a model drug. The IMM loaded microspheres of the graft copolymers, polystyrene-g-poly(lactide-co-glycolide) (PS-g-PLLGA), polystyrene-g-poly(lactic acid) (PS-g-PLLA) and poly(lactic-coglycolic acid) (PLLGA) were then prepared by a modified water-in-oil-in-water (w1/o/w2) double emulsion/solvent evaporation technique. The optimised microspheres were characterised by particle size, encapsulation efficiency, and surface morphology also; their degradation and release properties were studied in vitro. The degradation studies of three different types of microspheres showed that the PS backbone of the graft copolymers slows down the degradation rate compared to PLLGA.

  6. Hollow superparamagnetic PLGA/Fe 3O 4 composite microspheres for lysozyme adsorption

    NASA Astrophysics Data System (ADS)

    Yang, Qi; Wu, Yao; Lan, Fang; Ma, Shaohua; Xie, Liqin; He, Bin; Gu, Zhongwei

    2014-02-01

    Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe3O4 composite microspheres composed of an inner cavity, PLGA inner shell and Fe3O4 outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe3O4 nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 μm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g-1) and high efficiency in lysozyme adsorption.

  7. Hollow superparamagnetic PLGA/Fe3O4 composite microspheres for lysozyme adsorption.

    PubMed

    Yang, Qi; Wu, Yao; Lan, Fang; Ma, Shaohua; Xie, Liqin; He, Bin; Gu, Zhongwei

    2014-02-28

    Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe(3)O(4) composite microspheres composed of an inner cavity, PLGA inner shell and Fe(3)O(4) outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe(3)O(4) nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 μm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g(-1)) and high efficiency in lysozyme adsorption. PMID:24492410

  8. Pickering-type water-in-oil-in-water multiple emulsions toward multihollow nanocomposite microspheres.

    PubMed

    Maeda, Hayata; Okada, Masahiro; Fujii, Syuji; Nakamura, Yoshinobu; Furuzono, Tsutomu

    2010-09-01

    Multihollow hydroxyapatite (HAp)/poly(L-lactic acid) (PLLA) nanocomposite microspheres were readily fabricated by solvent evaporation from a "Pickering-type" water-in-(dichloromethane solution of PLLA)-in-water multiple emulsion stabilized with HAp nanoparticles. The multiple emulsion was stabilized with the aid of PLLA molecules used as a wettability modifier for HAp nanoparticles, although HAp nanoparticles did not work solely as particulate emulsifiers for Pickering-type emulsions consisting of pure dichloromethane and water. The interaction between PLLA and HAp nanoparticles at the oil-water interfaces plays a crucial role toward the preparation of stable multiple emulsion and multihollow microspheres.

  9. Solid evacuated microspheres of hydrogen

    DOEpatents

    Turnbull, Robert J.; Foster, Christopher A.; Hendricks, Charles D.

    1982-01-01

    A method is provided for producing solid, evacuated microspheres comprised of hydrogen. The spheres are produced by forming a jet of liquid hydrogen and exciting mechanical waves on the jet of appropriate frequency so that the jet breaks up into drops with a bubble formed in each drop by cavitation. The drops are exposed to a pressure less than the vapor pressure of the liquid hydrogen so that the bubble which is formed within each drop expands. The drops which contain bubbles are exposed to an environment having a pressure just below the triple point of liquid hydrogen and they thereby freeze giving solid, evacuated spheres of hydrogen.

  10. Nuclear fuel microsphere gamma analyzer

    DOEpatents

    Valentine, Kenneth H.; Long, Jr., Ernest L.; Willey, Melvin G.

    1977-01-01

    A gamma analyzer system is provided for the analysis of nuclear fuel microspheres and other radioactive particles. The system consists of an analysis turntable with means for loading, in sequence, a plurality of stations within the turntable; a gamma ray detector for determining the spectrum of a sample in one section; means for analyzing the spectrum; and a receiver turntable to collect the analyzed material in stations according to the spectrum analysis. Accordingly, particles may be sorted according to their quality; e.g., fuel particles with fractured coatings may be separated from those that are not fractured, or according to other properties.

  11. Synthesis and improved SERS performance of silver nanoparticles-decorated surface mesoporous silica microspheres

    NASA Astrophysics Data System (ADS)

    Jiang, Tao; Wang, Xiaolong; Zhang, Li; Zhou, Jun; Zhao, Ziqi

    2016-08-01

    This study reported the improved Raman enhancement ability of silver nanoparticles (Ag NPs) decorated on surface mesoporous silica microspheres (MSiO2@Ag) than that of Ag NPs on solid silica microspheres (SSiO2@Ag). These two kinds of hybrid structures were prepared by a facile single-step hydrothermal reaction with polyvinylpyrrolidone (PVP) serves as both a reductant and stabilizer. The as-synthesized MSiO2@Ag microspheres show more significant surface-enhanced Raman scattering (SERS) activity for 4-mercaptobenzoic acid (4MBA) than SSiO2@Ag microspheres with enhancement factors as 9.20 × 106 and 4.39 × 106, respectively. The proposed reason for the higher SERS activity is estimated to be the contribution of more Raman probe molecules at the mesoporous channels where an enhanced electromagnetic field exists. Such a field was identified by theoretical calculation result. The MSiO2@Ag microspheres were eventually demonstrated for the SERS detection of a typical chemical toxin namely methyl parathion with a detection limit as low as 1 × 10-3 ppm, showing its promising potential in biosensor application.

  12. An Electrochemical DNA Microbiosensor Based on Succinimide-Modified Acrylic Microspheres

    PubMed Central

    Ulianas, Alizar; Heng, Lee Yook; Hanifah, Sharina Abu; Ling, Tan Ling

    2012-01-01

    An electrochemical microbiosensor for DNA has been fabricated based on new acrylic microspheres modified with reactive N-acryloxysuccinimide (NAS) functional groups. Hydrophobic poly(n-butylacrylate-N-acryloxysuccinimide) microspheres were synthesized in an emulsion form with a simple one-step photopolymerization technique. Aminated DNA probe was attached to the succinimde functional group of the acrylic microspheres via covalent bonding. The hybridization of the immobilized DNA probe with the complementary DNA was studied by differential pulse voltametry using anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) as the electroactive hybridization label. The influences of many factors such as duration of DNA probe immobilization and hybridization, pH, type of ions, buffer concentrations, ionic strength, operational temperature and non-complementary DNA on the biosensor performance were evaluated. Under optimized conditions, the DNA microbiosensor demonstrated a linear response range to target DNA over a wide concentration range of 1.0 × 10−16 and 1.0 × 10−8 M with a lower limit of detection (LOD) of 9.46 × 10−17 M (R2 = 0.97). This DNA microbiosensor showed good reproducibility with 2.84% RSD (relative standard deviation) (n = 3). Application of the NAS-modified acrylic microspheres in the construction of DNA microbiosensor had improved the overall analytical performance of the resultant DNA microbiosensor when compared with other reported DNA biosensors using other nano-materials for membranes and microspheres as DNA immobilization matrices. PMID:22778594

  13. Bisphosphonate release profiles from magnetite microspheres.

    PubMed

    Miyazaki, Toshiki; Inoue, Tatsuya; Shirosaki, Yuki; Kawashita, Masakazu; Matsubara, Takao; Matsumine, Akihiko

    2014-10-01

    Hyperthermia has been suggested as a novel, minimally invasive cancer treatment method. After implantation of magnetic nano- or microparticles around a tumour through blood vessels, irradiation with alternating magnetic fields facilitates the efficient in situ hyperthermia even for deep-seated tumours. On the basis of this idea, if the microspheres are capable of delivering drugs, they could be promising multifunctional biomaterials effective for chemotherapy as well as hyperthermia. In the present study, magnetite microspheres were prepared by aggregation of the iron oxide colloid in water-in-oil (W/O) emulsion. The release behaviour of alendronate, a typical bisphosphonate, from the microspheres was examined in vitro as a model of the bone tumour prevention and treatment system. The alendronate was successfully incorporated onto the porous magnetite microspheres in vacuum conditions. The drug-loaded microspheres maintained their original spherical shapes even after shaking in ultrapure water for 3 days, suggesting that they have sufficient mechanical integrity for clinical use. It was attributed to high aggregation capability of the magnetite nanoparticles through van der Waals and weak magnetic attractions. The microspheres showed slow release of the alendronate in vitro, resulting from tight covalent or ionic interaction between the magnetite and the alendronate. The release rate was diffusion-controlled type and well controlled by the alendronate concentration in drug incorporation to the microspheres.

  14. Bisphosphonate release profiles from magnetite microspheres.

    PubMed

    Miyazaki, Toshiki; Inoue, Tatsuya; Shirosaki, Yuki; Kawashita, Masakazu; Matsubara, Takao; Matsumine, Akihiko

    2014-10-01

    Hyperthermia has been suggested as a novel, minimally invasive cancer treatment method. After implantation of magnetic nano- or microparticles around a tumour through blood vessels, irradiation with alternating magnetic fields facilitates the efficient in situ hyperthermia even for deep-seated tumours. On the basis of this idea, if the microspheres are capable of delivering drugs, they could be promising multifunctional biomaterials effective for chemotherapy as well as hyperthermia. In the present study, magnetite microspheres were prepared by aggregation of the iron oxide colloid in water-in-oil (W/O) emulsion. The release behaviour of alendronate, a typical bisphosphonate, from the microspheres was examined in vitro as a model of the bone tumour prevention and treatment system. The alendronate was successfully incorporated onto the porous magnetite microspheres in vacuum conditions. The drug-loaded microspheres maintained their original spherical shapes even after shaking in ultrapure water for 3 days, suggesting that they have sufficient mechanical integrity for clinical use. It was attributed to high aggregation capability of the magnetite nanoparticles through van der Waals and weak magnetic attractions. The microspheres showed slow release of the alendronate in vitro, resulting from tight covalent or ionic interaction between the magnetite and the alendronate. The release rate was diffusion-controlled type and well controlled by the alendronate concentration in drug incorporation to the microspheres. PMID:24854985

  15. Melanoidin and aldocyanoin microspheres: implications for chemical evolution and early precambrian micropaleontology.

    PubMed

    Kenyon, D H; Nissenbaum, A

    1976-04-01

    Two new classes of organic microspheres are described. One of them (melanoidin) is synthesized from amino acids and sugars in heated aqueous solutions. The other (aldocyanoin) is formed in aqueous solutions of ammonium cyanide and formaldehyde at room temperature. The general properties of these microspheres, including conditions of synthesis, size and shape, mechanical and pH stability, and solubility, are compared with corresponding properties of other "protocell" model systems. It is concluded that melanoidin and aldocyanoin microsphreres are plausible candidates for precellular units in the primitive hydrosphere. Since the bulk of the organic carbon in early Precambrian sediments is insoluble kerogen-melanoidin, it is suggested that some Precambrian "microfossils" may be abiotic melanoidin microspheres of the type described herein.

  16. Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites.

    PubMed

    Gu, Bing; Sun, Xuanhao; Papadimitrakopoulos, Fotios; Burgess, Diane J

    2016-04-28

    The aim of this study was to understand the polymer degradation and drug release mechanism from PLGA microspheres embedded in a PVA hydrogel. Two types of microspheres were prepared with different molecular weight PLGA polymers (approximately 25 and 7 kDa) to achieve different drug release profiles, with a 9-day lag phase and without a lag phase, respectively. The kinetics of water uptake into the microspheres coincided with the drug release profiles for both formulations. For the 25 kDa microspheres, minimal water uptake was observed in the early part of the lag phase followed by substantial water uptake at the later stages and in the drug release phase. For the 7 kDa microspheres, water uptake occurred simultaneously with drug release. Water uptake was approximately 2-3 times that of the initial microsphere weight for both formulations. The internal structure of the PLGA microspheres was evaluated using low temperature scanning electron microscopy (cryo-SEM). Burst drug release occurred followed by pore forming from the exterior to the core of both microspheres. A well-defined hydrogel/microsphere interface was observed. For the 25 kDa microspheres, internal pore formation and swelling occurred before the second drug release phase. The surface layer of the microspheres remained intact whereas swelling, and degradation of the core continued throughout the drug release period. In addition, microsphere swelling reduced glucose transport through the coatings in PBS media and this was considered to be a as a consequence of the increased thickness of the coatings. The combination of the swelling and microdialysis results provides a fresh understanding on the competing processes affecting molecular transport of bioanalytes (i.e. glucose) through these composite coatings during prolonged exposure in PBS. PMID:26965956

  17. Aceclofenac microspheres: quality by design approach.

    PubMed

    Deshmukh, Rameshwar K; Naik, Jitendra B

    2014-03-01

    The purpose of this study was to prepare polymeric microspheres containing aceclofenac by single emulsion [oil-in-water (o/w)] solvent evaporation method. Two biocompatible polymers, ethylcellulose, and Eudragit® RS100 were used in combination. Seven processing factors were investigated by Plackett-Burman design (PBD) in order to enhance the encapsulation efficiency of the microspheres. A Plackett-Burman design was employed by using the Design-Expert® software (Version-8.0.7.1). The resultant microspheres were characterized for their size, morphology, encapsulation efficiency, and drug release. Imaging of particles was performed by field emission scanning electron microscopy. Interaction between the drug and polymers were investigated by Fourier transform infrared (FTIR) spectroscopy, and X-ray powder diffractometry (XRPD). Graphical and mathematical analyses of the design showed that Eudragit® RS100, and polyvinyl alcohol (PVA) were significant negative effect on the encapsulation efficiency and identified as the significant factor determining the encapsulation efficiency of the microspheres. The low magnitudes of error and the significant values of R(2) in the present investigation prove the high prognostic ability of the design. The microspheres showed high encapsulation efficiency (70.15% to 83.82%). The microspheres were found to be discrete, oval with smooth surface. The FTIR analysis confirmed the compatibility of aceclofenac with the polymers. The XRPD revealed the dispersion of drug within microspheres formulation. Perfect prolonged drug release profile over 12h was achieved by a combination of ethylcellulose, and Eudragit® RS100 polymers. In conclusion, polymeric microspheres containing aceclofenac can be successfully prepared using the technique of experimental design, and these results helped in finding the optimum formulation variables for encapsulation efficiency of microspheres. PMID:24433918

  18. Reduction of ethylenediaminetetraacetic acid iron(III) by Klebsiella sp. FD-3 immobilized on iron(II, III) oxide poly (styrene-glycidyl methacrylate) magnetic porous microspheres: effects of inorganic compounds and kinetic study of effective diffusion in porous media.

    PubMed

    Zhou, Zuo-Ming; Wang, Xiao-Yan; Lin, Tian-Ming; Jing, Guo-Hua

    2014-11-01

    Fe3O4 poly (styrene-glycidyl methacrylate) magnetic porous microspheres (MPPMs) were introduced to immobilize Klebsiella sp. FD-3, an iron-reducing bacterium applied to reduce Fe(III)EDTA. The effects of potential inhibitors (S(2-), SO3(2-), NO3(-), NO2(-) and Fe(II)EDTA-NO) on Fe(III)EDTA reduction were investigated. S(2-) reacted with Fe(III)EDTA as an electron-shuttling compound and enhanced the reduction. But Fe(III)EDTA reduction was inhibited by SO3(2-) and Fe(II)EDTA-NO due to their toxic to microorganisms. Low concentrations of NO3(-) and NO2(-) accelerated Fe(III)EDTA reduction, but high concentrations inhibited the reduction, whether by free or immobilized FD-3. The immobilized FD-3 performed better than freely-suspended style. The substrate mass transfer and diffusion kinetics in the porous microspheres were calculated. The value of Thiele modulus and effectiveness factors showed that the intraparticle diffusion was fairly small and neglected in this carrier. Fe(III)EDTA reduction fitted first-order model at low Fe(III)EDTA concentration, and changed to zero-order model at high concentrations.

  19. SRNL POROUS WALL GLASS MICROSPHERES

    SciTech Connect

    Wicks, G; Leung Heung, L; Ray Schumacher, R

    2008-04-15

    The Savannah River National Laboratory (SRNL) has developed a new medium for storage of hydrogen and other gases. This involves fabrication of thin, Porous Walled, Hollow Glass Microspheres (PW-HGMs), with diameters generally in the range of 1 to several hundred microns. What is unique about the glass microballons is that porosity has been induced and controlled within the thin, one micron thick walls, on the scale of 10 to several thousand Angstroms. This porosity results in interesting properties including the ability to use these channels to fill the microballons with special absorbents and other materials, thus providing a contained environment even for reactive species. Gases can now enter the microspheres and be retained on the absorbents, resulting in solid-state and contained storage of even reactive species. Also, the porosity can be altered and controlled in various ways, and even used to filter mixed gas streams within a system. SRNL is involved in about a half dozen different programs involving these PW-HGMs and an overview of some of these activities and results emerging are presented.

  20. Organic aerogel microspheres and fabrication method therefor

    DOEpatents

    Mayer, S.T.; Kong, F.M.; Pekala, R.W.; Kaschmitter, J.L.

    1996-04-16

    Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  1. Organic aerogel microspheres and fabrication method therefor

    DOEpatents

    Mayer, Steven T.; Kong, Fung-Ming; Pekala, Richard W.; Kaschmitter, James L.

    1996-01-01

    Organic aerogel microspheres which can be used in capacitors, batteries, thermal insulation, adsorption/filtration media, and chromatographic packings, having diameters ranging from about 1 micron to about 3 mm. The microspheres can be pyrolyzed to form carbon aerogel microspheres. This method involves stirring the aqueous organic phase in mineral oil at elevated temperature until the dispersed organic phase polymerizes and forms nonsticky gel spheres. The size of the microspheres depends on the collision rate of the liquid droplets and the reaction rate of the monomers from which the aqueous solution is formed. The collision rate is governed by the volume ratio of the aqueous solution to the mineral oil and the shear rate, while the reaction rate is governed by the chemical formulation and the curing temperature.

  2. Efficient photocatalytic removal of NO in indoor air with hierarchical bismuth oxybromide nanoplate microspheres under visible light.

    PubMed

    Ai, Zhihui; Ho, Wingkei; Lee, Shuncheng; Zhang, Lizhi

    2009-06-01

    In this study, hierarchical bismuth oxybromide (BiOBr) nanoplate microspheres were used to remove NO in indoor air under visible light irradiation. The BiOBr microspheres were synthesized with a nonaqueous sol-gel method by using bismuth nitrate and cetyltrimethyl ammonium bromide as the precursors. On degradation of NO under visible light irradiation (lambda > 420 nm) at 400 part-per-billion level, which is typical concentration for indoor air quality, these nonaqueous sol-gel synthesized hierarchical BiOBr microspheres exhibited superior photocatalytic activity to the chemical precipitation synthesized counterpart BiOBr bulk powder and Degussa TiO2 P25 as well as C doped TiO2. The excellent catalytic activity and the long-term activity of nonaqueous sol-gel synthesized BiOBr microspheres were attributed to their special hierarchical structure, which was favorable for the diffusion of intermediates and final products of NO oxidation. Ion chromatograph results confirmed that nitric acid was produced on the surface of BiOBr microspheres during the photooxidation of NO in gas phase. This work suggests that the nonaqueous sol-gel synthesized BiOBr nanoplate microspheres are promising photocatalytic materials for indoor air purification. PMID:19569343

  3. Development of molecularly imprinted microspheres for the fast uptake of 4-cumylphenol from water and soil samples.

    PubMed

    Narula, Priyanka; Kaur, Varinder; Singh, Raghubir; Kansal, Sushil Kumar

    2014-11-01

    Molecularly imprinted microspheres containing binding sites for the extraction of 4-cumylphenol have been prepared for the first time. The imprinted microspheres were synthesized by a precipitation method using 4-cumylphenol as a template molecule, methacrylic acid as a functional monomer and divinylbenzene-80 as a cross-linker for polymer network formation. The formation and the morphology of molecularly imprinted microspheres were well characterized using infrared spectroscopy, thermogravimetric studies, and scanning electron microscopy. The Brunauer-Emmett-Teller analysis revealed the high surface area of the sorbent indicating formation of molecularly imprinted microspheres. The developed microspheres were employed as a sorbent for the solid-phase extraction of 4-cumylphenol and showed fast uptake kinetics. The sorption parameters were optimized to achieve efficient sorption of the template molecule, like pH, quantity of molecularly imprinted microspheres, time required for equilibrium set-up, sorption kinetics, and adsorption isotherm. A standard method was developed to analyze the sorbed sample quantitatively at 279 nm using high-performance liquid chromatography with diode array detection. It was validated by determining target analyte from synthetic samples, bottled water, spiked tap water, and soil samples. The prepared material is a selective and robust sorbent with good reusability. PMID:25196136

  4. Novel preparation method for sustained-release PLGA microspheres using water-in-oil-in-hydrophilic-oil-in-water emulsion

    PubMed Central

    Hong, Xiaoyun; Wei, Liangming; Ma, Liuqing; Chen, Yinghui; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    An increasing number of drugs are needing improved formulations to optimize patient compliance because of their short half-lives in blood. Sustained-release formulations of drugs are often required for long-term efficacy, and microspheres are among the most popular ones. When drugs are encapsulated into microsphere formulations, different methods of preparation need to be used according to specific clinical requirements and the differing physicochemical characteristics of individual drugs. In this work, we developed a novel method for sustained-release drug delivery using a water-in-oil-in-hydrophilic oil-in-water (w/o/oh/w) emulsion to encapsulate a drug into poly(lactic-co-glycolic acid) (PLGA) microspheres. Different effects were achieved by varying the proportions and concentrations of hydrophilic oil and PLGA. Scanning electron and optical microscopic images showed the surfaces of the microspheres to be smooth and that their morphology was spherical. Microspheres prepared using the w/o/oh/w emulsion were able to load protein efficiently and had sustained-release properties. These results indicate that the above-mentioned method might be useful for developing sustained-release microsphere formulations in the future. PMID:23882140

  5. Coating gigaporous polystyrene microspheres with cross-linked poly(vinyl alcohol) hydrogel as a rapid protein chromatography matrix.

    PubMed

    Qu, Jian-Bo; Huan, Guan-Sheng; Chen, Yan-Li; Zhou, Wei-Qing; Liu, Jian-Guo; Huang, Fang

    2014-08-13

    Gigaporous polystyrene (PS) microspheres were hydrophilized by in situ polymerization to give a stable cross-linked poly(vinyl alcohol) (PVA) hydrogel coating, which can shield proteins from the hydrophobic PS surface underneath. The amination of microspheres (PS-NH2) was first carried out through acetylization, oximation and reduction, and then 4,4'-azobis (4-cyanovaleric acid) (ACV), a polymerization initiator, was covalently immobilized on PS-NH2 through amide bond formation, and the cross-linked poly(vinyl acetate) (PVAc) was prepared by radical polymerization at the surfaces of ACV-immobilized PS microspheres (PS-ACV). Finally, the cross-linked PVA hydrogel coated gigaporous PS microspheres (PS-PVA) was easily achieved through alcoholysis of PVAc. Results suggested that the PS microspheres were effectively coated with cross-linked PVA hydrogel, where the gigaporrous structure remained under optimal conditions. After hydrophilic modification (PS-PVA), the protein-resistant ability of microspheres was greatly improved. The hydroxyl-rich PS-PVA surface can be easily derivatized by classical chemical methods. Performance advantages of the PS-PVA column in flow experiment include good permeability, low backpressure, and mechanical stability. These results indicated that PS-PVA should be promising in rapid protein chromatography.

  6. Nanostructuring the surface of dual responsive hollow polymer microspheres for versatile utilization in nanomedicine-related applications.

    PubMed

    Chatzipavlidis, A; Bilalis, P; Tziveleka, L-A; Boukos, N; Charitidis, C A; Kordas, G

    2013-07-30

    The design and fabrication of hollow polymer microspheres responsive to various stimuli comprises a promising approach for the development of multifunctional and efficient systems for various nanomedicine-related applications. In this paper, we present the preparation of poly(methacrylic acid-co-N,N'-methylenebis(acrylamide)-co-poly(ethylene glycol) methyl ether methacrylate-co-N,N'-bis(acryloyl)cystamine) (PMAA(S-S)) hollow microspheres following a two-stage distillation precipitation polymerization procedure. Magnetic and silver nanocrystals were chemically grown on the surface of the hollow polymer microspheres, resulting in a composite system with interesting properties. We evaluated the performance of the composite hollow microspheres as magnetic hyperthermia mediators and their surface-enhanced Raman spectroscopy activity. Assessment of Daunorubicin-loaded PMAA(S-S) hollow microspheres performance as effective drug carriers was carried out through drug release experiments upon application of different pH and reducing conditions. pH and redox responsiveness as well as basic mechanisms of release profiles are discussed. Furthermore, in vitro cytotoxicity of empty and drug-loaded PMAA(S-S) hollow microspheres against MCF-7 cancer cells was investigated in order to evaluate their performance as drug carriers.

  7. Development of molecularly imprinted microspheres for the fast uptake of 4-cumylphenol from water and soil samples.

    PubMed

    Narula, Priyanka; Kaur, Varinder; Singh, Raghubir; Kansal, Sushil Kumar

    2014-11-01

    Molecularly imprinted microspheres containing binding sites for the extraction of 4-cumylphenol have been prepared for the first time. The imprinted microspheres were synthesized by a precipitation method using 4-cumylphenol as a template molecule, methacrylic acid as a functional monomer and divinylbenzene-80 as a cross-linker for polymer network formation. The formation and the morphology of molecularly imprinted microspheres were well characterized using infrared spectroscopy, thermogravimetric studies, and scanning electron microscopy. The Brunauer-Emmett-Teller analysis revealed the high surface area of the sorbent indicating formation of molecularly imprinted microspheres. The developed microspheres were employed as a sorbent for the solid-phase extraction of 4-cumylphenol and showed fast uptake kinetics. The sorption parameters were optimized to achieve efficient sorption of the template molecule, like pH, quantity of molecularly imprinted microspheres, time required for equilibrium set-up, sorption kinetics, and adsorption isotherm. A standard method was developed to analyze the sorbed sample quantitatively at 279 nm using high-performance liquid chromatography with diode array detection. It was validated by determining target analyte from synthetic samples, bottled water, spiked tap water, and soil samples. The prepared material is a selective and robust sorbent with good reusability.

  8. Novel preparation method for sustained-release PLGA microspheres using water-in-oil-in-hydrophilic-oil-in-water emulsion.

    PubMed

    Hong, Xiaoyun; Wei, Liangming; Ma, Liuqing; Chen, Yinghui; Liu, Zhenguo; Yuan, Weien

    2013-01-01

    An increasing number of drugs are needing improved formulations to optimize patient compliance because of their short half-lives in blood. Sustained-release formulations of drugs are often required for long-term efficacy, and microspheres are among the most popular ones. When drugs are encapsulated into microsphere formulations, different methods of preparation need to be used according to specific clinical requirements and the differing physicochemical characteristics of individual drugs. In this work, we developed a novel method for sustained-release drug delivery using a water-in-oil-in-hydrophilic oil-in-water (w/o/oh/w) emulsion to encapsulate a drug into poly(lactic-co-glycolic acid) (PLGA) microspheres. Different effects were achieved by varying the proportions and concentrations of hydrophilic oil and PLGA. Scanning electron and optical microscopic images showed the surfaces of the microspheres to be smooth and that their morphology was spherical. Microspheres prepared using the w/o/oh/w emulsion were able to load protein efficiently and had sustained-release properties. These results indicate that the above-mentioned method might be useful for developing sustained-release microsphere formulations in the future.

  9. Simultaneous nano- and micro-scale control of nanofibrous microspheres self-assembled from star-shaped polymers

    PubMed Central

    Zhang, Zhanpeng; Marson, Ryan L.; Ge, Zhishen; Glotzer, Sharon C.; Ma, Peter X.

    2015-01-01

    The mechanism underlying the multi-scale self-assembly of star-shaped polymers into non-hollow, hollow, and spongy nanofibrous microspheres is reported. Star-shaped poly(L-lactic acid) polymers with varying arm-numbers and arm-lengths are synthesized, dissolved in tetrahydrofuran, emulsified in glycerol, and thermally-induced to phase separate, resulting in microspheres that are either smooth or fibrous on the nano-scale, and either non-hollow, hollow, or spongy on the micro-scale. Molecular architecture and the hydroxyl density are shown to control assembly and morphology at both nano- and micro-scales. Nanofibers form only when the arm length is sufficiently long, while an increase in hydroxyl density causes the microspheres to change from non-hollow to hollow to spongy. We demonstrate via both experiments of capping or doubling the hydroxyl end groups and dissipative particle dynamics simulations that the affinity of hydroxyl to glycerol is critical to stabilizing the micro-scale structure. A “phase diagram” was constructed for the six types of microspheres in relation to the molecular structures of the star-shaped polymers. The proposed mechanism explains how star-shaped polymers self-assemble into various microspheres, and guides us to simultaneously control both nano- and micro-features of the microspheres. PMID:26009995

  10. Sustained-release G-CSF microspheres using a novel solid-in-oil-in-oil-in-water emulsion method

    PubMed Central

    Liu, Guang; Hong, Xiaoyun; Jiang, Mier; Yuan, Weien

    2012-01-01

    Background The main treatments for cancers are still chemotherapy and radiotherapy for intermediate-stage cancer and terminal cancer. However, the therapeutic methods often result in a decreased neutrophilic granulocyte count and other side effects. In this study, in order to improve the neutrophilic granulocyte levels in the blood after radiotherapy and chemotherapy, we developed a sustained-release granulocyte colony–stimulating factor (G-CSF) microsphere formulation using a novel solid-in-oil-in-oil-in-water (S/O/O/W) emulsification method. Methods G-CSF was loaded into dextran nanoparticles by freezing-induced phase separation, and then the G-CSF–loaded nanoparticles were encapsulated into sustained-release poly(lactic-co- glycolic acid) microspheres using S/O/O/W emulsification. The control microspheres were also prepared through W/O/W emulsification. The performance of the two microsphere formulations was investigated both in vitro and in vivo. Results The microspheres for the controlled release of G-CSF in a zero-order or near-zero-order pattern were provided for 2 weeks. The in vitro cumulative G-CSF release kept over 90% of its bioactivity, which was proved by a NFS-60 cell line growth assay. The microspheres of the control group fabricated by W/O/W emulsification maintained less then half of its bioactivity. The in vivo efficacy of microspheres made using the S/O/O/W method was higher than those using the W/O/W method. Conclusion These results suggested that the microspheres prepared by the S/O/O/W method had increased neutrophil activity compared to those prepared by W/O/W. PMID:22923993

  11. Method for introduction of gases into microspheres

    DOEpatents

    Hendricks, Charles D.; Koo, Jackson C.; Rosencwaig, Allan

    1981-01-01

    A method for producing small hollow glass spheres filled with a gas by introduction of the gas during formation of the hollow glass spheres. Hollow glass microspheres having a diameter up to about 500.mu. with both thin walls (0.5 to 4.mu.) and thick walls (5 to 20.mu.) that contain various fill gases, such as Ar, Kr, Xe, Br, DT, H.sub.2, D.sub.2, He, N.sub.2, Ne, CO.sub.2, etc. in the interior thereof, can be produced by the diffusion of the fill gas or gases into the microsphere during the formation thereof from a liquid droplet of glass-forming solution. This is accomplished by filling at least a portion of the multiple-zone drop-furnace used in producing hollow microspheres with the gas or gases of interest, and then taking advantage of the high rate of gaseous diffusion of the fill gas through the wall of the gel membrane before it transforms into a glass microsphere as it is processed in the multiple-zone furnace. Almost any gas can be introduced into the inner cavity of a glass microsphere by this method during the formation of the microsphere provided that the gas is diffused into the gel membrane or microsphere prior to its transformation into glass. The process of this invention provides a significant savings of time and related expense of filling glass microspheres with various gases. For example, the time for filling a glass microballoon with 1 atmosphere of DT is reduced from about two hours to a few seconds.

  12. Hydrogen transport and storage in engineered microspheres

    SciTech Connect

    Rambach, G.; Hendricks, C.

    1996-10-01

    This project is a collaboration between Lawrence Livermore National Laboratory (LLNL) and W.J. Schafer Associates (WJSA). The authors plan to experimentally verify the performance characteristics of engineered glass microspheres that are relevant to the storage and transport of hydrogen for energy applications. They will identify the specific advantages of hydrogen transport by microspheres, analyze the infrastructure implications and requirements, and experimentally measure their performance characteristics in realistic, bulk storage situations.

  13. Hierarchically assembled Au microspheres and sea urchin-like architectures: formation mechanism and SERS study

    NASA Astrophysics Data System (ADS)

    Wang, Xiansong; Yang, Da-Peng; Huang, Peng; Li, Min; Li, Chao; Chen, Di; Cui, Daxiang

    2012-11-01

    The hierarchically assembled Au microspheres/sea urchin-like structures have been synthesized in aqueous solution at room temperature with and without proteins (bovine serum albumin, BSA) as mediators. The average diameter of an individual Au microsphere is 300-600 nm, which is composed of some compact nanoparticles with an average diameter of about 15 nm. Meanwhile, the sea urchin-like Au architecture exhibits an average diameter of 600-800 nm, which is made up of some nanopricks with an average length of 100-200 nm. These products are characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electronic microscopy (TEM). It is found that the BSA and ascorbic acid (AA) have great effects on the morphology of the resulting products. Two different growth mechanisms are proposed. The study on surface enhanced Raman scattering (SERS) activities is also carried out between Au microspheres and Au sea urchin-like architectures. It is found that Au urchin-like architectures possess much higher SERS activity than the Au microspheres. Our work may shed light on the design and synthesis of hierarchically self-assembled 3D micro/nano-architectures for SERS, catalysis and biosensors.The hierarchically assembled Au microspheres/sea urchin-like structures have been synthesized in aqueous solution at room temperature with and without proteins (bovine serum albumin, BSA) as mediators. The average diameter of an individual Au microsphere is 300-600 nm, which is composed of some compact nanoparticles with an average diameter of about 15 nm. Meanwhile, the sea urchin-like Au architecture exhibits an average diameter of 600-800 nm, which is made up of some nanopricks with an average length of 100-200 nm. These products are characterized by means of scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electronic microscopy (TEM). It is found that the BSA and ascorbic acid (AA) have great effects on the morphology of

  14. Coacervate microspheres as carriers of recombinant adenoviruses.

    PubMed

    Kalyanasundaram, S; Feinstein, S; Nicholson, J P; Leong, K W; Garver, R I

    1999-01-01

    The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by difficulties in directing the viruses to specific sites and by the requirement for bolus administration, both of which limit the efficiency of target tissue infection. As a first step toward overcoming these limitations, rAds were encapsulated in coacervate microspheres comprised of gelatin and alginate followed by stabilization with calcium ions. Ultrastructural evaluation showed that the microspheres formed in this manner were 0.8-10 microM in diameter, with viruses evenly distributed. The microspheres achieved a sustained release of adenovirus with a nominal loss of bioactivity. The pattern of release and the total amount of virus released was modified by changes in microsphere formulation. Administration of the adenovirus-containing microspheres to human tumor nodules engrafted in mice showed that the viral transgene was transferred to the tumor cells. It is concluded that coacervate microspheres can be used to encapsulate bioactive rAd and release it in a time-dependent manner.

  15. Demonstration of Microsphere Insulation in Cryogenic Vessels

    NASA Astrophysics Data System (ADS)

    Baumgartner, R. G.; Myers, E. A.; Fesmire, J. E.; Morris, D. L.; Sokalski, E. R.

    2006-04-01

    While microspheres have been recognized as a legitimate insulation material for decades, actual use in full-scale cryogenic storage tanks has not been demonstrated until now. The performance and life-cycle-cost advantages previously predicted have now been proven. Most bulk cryogenic storage tanks are insulated with either multilayer insulation (MLI) or perlite. Microsphere insulation, consisting of hollow glass bubbles, combines in a single material the desirable properties that other insulations only have individually. The material has high crush strength, low density, is noncombustible, and performs well in soft vacuum. These properties were proven during recent field testing of two 22,700-L (6,000-gallon) liquid nitrogen tanks, one insulated with microsphere insulation and the other with perlite. Normal evaporation rates (NER) for both tanks were monitored with precision test equipment and insulation levels within the tanks were observed through view ports as an indication of insulation compaction. Specific industrial applications were evaluated based on the test results and beneficial properties of microsphere insulation. Over-the-road trailers previously insulated with perlite will benefit not only from the reduced heat leak, but also the reduced mass of microsphere insulation. Economic assessments for microsphere-insulated cryogenic vessels including life-cycle cost are also presented.

  16. Coenzyme autocatalytic network on the surface of oil microspheres as a model for the origin of life.

    PubMed

    Sharov, Alexei A

    2009-04-22

    Coenzymes are often considered as remnants of primordial metabolism, but not as hereditary molecules. I suggest that coenzyme-like molecules (CLMs) performed hereditary functions before the emergence of nucleic acids. Autocatalytic CLMs modified (encoded) surface properties of hydrocarbon microspheres, to which they were anchored, and these changes enhanced autocatalysis and propagation of CLMs. Heredity started from a single kind of self-reproducing CLM, and then evolved into more complex coenzyme autocatalytic networks containing multiple kinds of CLMs. Polymerization of CLMs on the surface of microspheres and development of template-based synthesis is a potential evolutionary path towards the emergence of nucleic acids.

  17. Curvature capillary migration of microspheres.

    PubMed

    Sharifi-Mood, Nima; Liu, Iris B; Stebe, Kathleen J

    2015-09-14

    We address the question: how does capillarity propel microspheres along curvature gradients? For a particle on a fluid interface, there are two conditions that can apply at the three phase contact line: either the contact line adopts an equilibrium contact angle, or it can be pinned by kinetic trapping, e.g. at chemical heterogeneities, asperities, or other pinning sites on the particle surface. We formulate the curvature capillary energy for both scenarios for particles smaller than the capillary length and far from any pinning boundaries. The scale and range of the distortion made by the particle are set by the particle radius; we use singular perturbation methods to find the distortions and to rigorously evaluate the associated capillary energies. For particles with equilibrium contact angles, contrary to the literature, we find that the capillary energy is negligible, with the first contribution bounded to fourth order in the product of the particle radius and the deviatoric curvature of the host interface. For pinned contact lines, we find curvature capillary energies that are finite, with a functional form investigated previously by us for disks and microcylinders on curved interfaces. In experiments, we show microspheres migrate along deterministic trajectories toward regions of maximum deviatoric curvature with curvature capillary energies ranging from 6 × 10(3)-5 × 10(4)kBT. These data agree with the curvature capillary energy for the case of pinned contact lines. The underlying physics of this migration is a coupling of the interface deviatoric curvature with the quadrupolar mode of nanometric disturbances in the interface owing to the particle's contact line undulations. This work is an example of the major implications of nanometric roughness and contact line pinning for colloidal dynamics.

  18. Electrospinning Growth Factor Releasing Microspheres into Fibrous Scaffolds

    PubMed Central

    Whitehead, Tonya J.; Sundararaghavan, Harini G.

    2014-01-01

    This procedure describes a method to fabricate a multifaceted substrate to direct nerve cell growth. This system incorporates mechanical, topographical, adhesive and chemical signals. Mechanical properties are controlled by the type of material used to fabricate the electrospun fibers. In this protocol we use 30% methacrylated Hyaluronic Acid (HA), which has a tensile modulus of ~500 Pa, to produce a soft fibrous scaffold. Electrospinning on to a rotating mandrel produces aligned fibers to create a topographical cue. Adhesion is achieved by coating the scaffold with fibronectin. The primary challenge addressed herein is providing a chemical signal throughout the depth of the scaffold for extended periods. This procedure describes fabricating poly(lactic-co-glycolic acid) (PLGA) microspheres that contain Nerve Growth Factor (NGF) and directly impregnating the scaffold with these microspheres during the electrospinning process. Due to the harsh production environment, including high sheer forces and electrical charges, protein viability is measured after production. The system provides protein release for over 60 days and has been shown to promote primary nerve cell growth. PMID:25178038

  19. Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

    PubMed Central

    Yao, Shenglian; Liu, Huiying; Yu, Shukui; Li, Yuanyuan; Wang, Xiumei; Wang, Luning

    2016-01-01

    The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system. In this study, two kind of aqueous model drugs with different molecule weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray. In the preparation process, the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution. The emulsion was then electrosprayed to fabricate drug-nanoencapsulated PLGA microspheres. The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase (Vw/Vo) and the molecule weight of model drugs. Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to Vw/Vo. With the increase of the volume ratio of aqueous drug phase, the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate. Moreover, BSA showed a slower release rate from PLGA microspheres comparing to Congo red, which indicated the drug release rate could be affected by not only Vw/Vo but also the molecule weight of model drug. In brief, the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple system to achieve controlled drug release at a desired rate satisfying the need of the practices.

  20. Bioresorbable microspheres by spinning disk atomization as injectable cell carrier: from preparation to in vitro evaluation.

    PubMed

    Senuma, Y; Franceschin, S; Hilborn, J G; Tissières, P; Bisson, I; Frey, P

    2000-06-01

    Vesico-ureteral reflux, a common pathology in children, can be treated cystoscopically by injection of a bulking material underneath the most distal, intramural ureter, which forces the latter to do a detour, increasing its submucosal path. This increase of the length of the submucosal path of the ureter within the bladder is directly responsible for the anti-reflux effect. So far Teflon and collagen paste have been commonly used as bulking materials. We suggest replacing these materials by living tissue consisting of bladder smooth muscle, normally present at this location. The aim of this work is to provide a long-term effective treatment by producing bioresorbable microspheres which can act as a support matrix and an entrapment substance for bladder smooth muscle cells, with the goal of an in vivo transfer of the in vitro cultured cells with a minimal surgical procedure. By the use of Spinning Disk Atomization, which has specifically been developed for this purpose, we have shown two methods for the preparation of porous poly(lactic acid) microspheres with tunable sizes from 160 to 320 microm. The controlled solvent burst method has shown the advantage over the crystal leaching method in the direct creation of microspheres with large closed pores, by atomizing the polymer solution in controlled temperature conditions. Microspheres with various closed pore structures have thus been prepared. The innovation of this work is in the direct and rapid formation of porous microspheres with a pore morphology which is designed to create cavities suitable for adherence and growth of cells by adapting the temperature conditions of atomization. Injection tests have shown promising results in using these cell-loaded microspheres for future non-invasive tissue engineering. PMID:10817266

  1. Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

    PubMed Central

    Yao, Shenglian; Liu, Huiying; Yu, Shukui; Li, Yuanyuan; Wang, Xiumei; Wang, Luning

    2016-01-01

    The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system. In this study, two kind of aqueous model drugs with different molecule weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray. In the preparation process, the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution. The emulsion was then electrosprayed to fabricate drug-nanoencapsulated PLGA microspheres. The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase (Vw/Vo) and the molecule weight of model drugs. Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to Vw/Vo. With the increase of the volume ratio of aqueous drug phase, the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate. Moreover, BSA showed a slower release rate from PLGA microspheres comparing to Congo red, which indicated the drug release rate could be affected by not only Vw/Vo but also the molecule weight of model drug. In brief, the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple system to achieve controlled drug release at a desired rate satisfying the need of the practices. PMID:27699061

  2. Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature

    PubMed Central

    Qutachi, Omar; Vetsch, Jolanda R.; Gill, Daniel; Cox, Helen; Scurr, David J.; Hofmann, Sandra; Müller, Ralph; Quirk, Robin A.; Shakesheff, Kevin M.; Rahman, Cheryl V.

    2014-01-01

    Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(dl-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84 ± 24 μm for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2 min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37 °C to form scaffold structures. The average compressive strength of the scaffolds after 24 h at 37 °C was 0.9 ± 0.1 MPa, and the average Young’s modulus was 9.4 ± 1.2 MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54 ± 38 μm. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro. PMID:25152354

  3. Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheres.

    PubMed

    Berkland, Cory; Kipper, Matt J; Narasimhan, Balaji; Kim, Kyekyoon Kevin; Pack, Daniel W

    2004-01-01

    A thorough understanding of the factors affecting drug release mechanisms from surface-erodible polymer devices is critical to the design of optimal delivery systems. Poly(sebacic anhydride) (PSA) microspheres were loaded with three model drug compounds (rhodamine B, p-nitroaniline and piroxicam) with a range of polarities (water solubilities). The drug release profiles from monodisperse particles of three different sizes were compared to release from polydisperse microspheres. Each of the model drugs exhibited different release mechanisms. Drug distribution within the polymer was investigated by laser scanning confocal microscopy and scanning electron microscopy. Rhodamine, the most hydrophilic compound investigated, was localized strongly toward the microsphere surface, while the much more hydrophobic compound, piroxicam, distributed more evenly. Furthermore, all three compounds were most uniformly distributed in the smallest microspheres, most likely due to the competing effects of drug diffusion out of the nascent polymer droplets and the precipitation of polymer upon solvent extraction, which effectively "traps" the drug in the polymer matrix. The differing drug distributions were manifested in the drug release profiles. Rhodamine was released very quickly independent of microsphere size. Thus, extended release profiles may not be obtainable if the drug strongly redistributes in the microspheres. The release of p-nitroaniline was more prolonged, but still showed little dependence on microsphere size. Hence, when water-soluble drugs are encapsulated with hydrophobic polymers, it may be difficult to tailor release profiles by controlling microsphere size. The piroxicam-loaded microspheres exhibit the most interesting release profiles, showing that release duration can be increased by decreasing microsphere size, resulting in a more uniform drug distribution. PMID:14684277

  4. Sustained-release delivery of octreotide from biodegradable polymeric microspheres.

    PubMed

    Rhee, Yun-Seok; Sohn, MinJi; Woo, Byung H; Thanoo, B C; DeLuca, Patrick P; Mansour, Heidi M

    2011-12-01

    The study reports on the drug release behavior of a potent synthetic somatostatin analogue, octreotide acetate, from biocompatible and biodegradable microspheres composed of poly-lactic-co-glycolic acid (PLGA) following a single intramuscular depot injection. The serum octreotide levels of three Oakwood Laboratories formulations and one Sandostatin LAR(®) formulation were compared. Three formulations of octreotide acetate-loaded PLGA microspheres were prepared by a solvent extraction and evaporation procedure using PLGA polymers with different molecular weights. The in vivo drug release study was conducted in male Sprague-Dawley rats. Blood samples were taken at predetermined time points for up to 70 days. Drug serum concentrations were quantified using a radioimmunoassay procedure consisting of radiolabeled octreotide. The three octreotide PLGA microsphere formulations and Sandostatin LAR(®) all showed a two-phase drug release profile (i.e., bimodal). The peak serum drug concentration of octreotide was reached in 30 min for all formulations followed by a decline after 6 h. Following this initial burst and decline, a second-release phase occurred after 3 days. This second-release phase exhibited sustained-release behavior, as the drug serum levels were discernible between days 7 and 42. Using pharmacokinetic computer simulations, it was estimated that the steady-state octreotide serum drug levels would be predicted to fall in the range of 40-130 pg/10 μL and 20-100 pg/10 μL following repeat dosing of the Oakwood formulations and Sandostatin LAR(®) every 28 days and every 42 days at a dose of 3 mg/rat, respectively.

  5. Preparation of uniform-sized exenatide-loaded PLGA microspheres as long-effective release system with high encapsulation efficiency and bio-stability.

    PubMed

    Qi, Feng; Wu, Jie; Fan, Qingze; He, Fan; Tian, Guifang; Yang, Tingyuan; Ma, Guanghui; Su, Zhiguo

    2013-12-01

    Exenatide-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres hold great potential as a drug delivery system to treat type 2 diabetes mellitus (T2DM) because they can overcome the shortcoming of exenatide's short half-life and realize sustained efficacy. However, conventional preparation methods often lead to microspheres with a broad size distribution, which in turn would cause poor preparation repeatability, drug efficacy and so forth. In this study, we used Shirasu Porous Glass (SPG) premix membrane emulsification technique characterized with high trans-membrane flux and size controllability to prepare uniform-sized PLGA microspheres. By optimizing trans-membrane pressure and PVA concentration in external aqueous phase, uniform-sized PLGA microspheres with large size (around 20μm) were successfully obtained. To achieve high encapsulation efficiency (EE) and improve in vitro release behavior, we have carefully examined the process parameters. Our results show that using ultrasonication to form primary emulsion, microspheres with high EE were easily obtained, but the rate of in vitro release was very slow. Instead, high EE and appropriate in vitro release were achieved when homogenization with optimized time and speed were employed. Besides, we also systematically investigated the effect of formulations on loading efficiency (LE) as well as the relationship between the resultant size of the microspheres and pore size of the membrane. Finally, through RP-HPLC and CD spectra analysis, we have demonstrated that the bio-stability of exenatide in microspheres was preserved during the preparation process.

  6. Production of microspheres with surface amino groups from blends of Poly(Lactide-co-glycolide) and Poly(epsilon-CBZ-L-lysine) and use for encapsulation.

    PubMed

    Zheng, J; Hornsby, P J

    1999-01-01

    Microspheres were formed from blends of the biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) together with poly(epsilon-CBZ-L-lysine) (PCBZL) by a double-emulsification/solvent evaporation technique. The size of the microspheres formed by this method was dependent both on the total concentration of the polymers and on the ratio of PLGA to PCBZL. The use of the microspheres for encapsulation was demonstrated by the inclusion of a solution of Texas Red fluorescent dye. Lysine epsilon-amino groups on the surface of the microspheres were deprotected by acid hydrolysis or lithium/liquid ammonia reduction. Acid hydrolysis damaged the surface of the microspheres as assessed by scanning electron microscopy, whereas deprotection by lithium/ammonia produced less damage and allowed the retention of encapsulated dye solution. The surface lysine groups made available on the surface of the microspheres could be used to covalently link a variety of biologically active molecules to alter their in vivo properties and allow targeting to specific cell types.

  7. Overexpression of GRF encapsulated in PLGA microspheres in animal skeletal muscle induces body weight gain.

    PubMed

    Zhang, Yong-liang; Ren, Xiao-hui; Liu, Song-cai; Dai, Jian-wei; Hao, Lin-lin; Jiang, Qing-yan

    2007-01-01

    Biodegradable nanospheres or microspheres have been widely used as a sustained release system for the delivery of bioagents. In the present study, injectable sustained-release growth hormone-releasing factor (GRF) (1-32) microspheres were prepared by a double emulsion-in liquid evaporation process using biodegradable polylactic-co-glycolic acid (PLGA) as the carrier. The entrapment efficiency was 89.79% and the mean particle size was 4.41 mum. The microspheres were injected into mouse tibialis muscle. After 30 days, mice injected with GRF (1-32) microspheres (group I) gained significantly more weight than any other treatment group, including mice injected with the naked plasmid (group II) (10.26 +/- 0.13 vs. 9.09 +/- 0.56; P < 0.05), a mixture of microspheres and plasmid (group III) (10.26 +/- 0.13 vs. 8.57 +/- 0.02; P < 0.05), or saline (IV) (10.26 +/- 0.13 vs. 6.47 +/- 0.26; P < 0.05). In addition, mice treated with the GRF (1-32) microspheres exhibited the highest expression levels of GRF as detected by PCR, RT-PCR, and ELISA (mean 2.56 +/- 0.40, P < 0.05, overall comparison of treatment with groups II, III, and IV). Additionally, rabbits were injected in the tibialis muscle with the same treatments described above. After 30 days, the group treated with GRF (1-32) microspheres gained the most weight. At day 30 postinjection, weight gain in group I was 63.93% higher than group II (plasmid) (877.10 +/- 24.42 vs. 535.05 +/- 26.38; P < 0.05), 108.59% higher than group III (blank MS) (877.10 +/- 24.42 vs. 420.50 +/- 19.39; P < 0.05), and 93.94% higher than group IV (saline) (877.10 +/- 24.42 vs. 452.25 +/- 27.38; P < 0.05). Furthermore, IGF-1 levels in the serum from GRF microsphere-treated group were elevated relative to all other groups. The present results suggest that encapsulation of GRF with PLGA increases GRF gene expression in muscle after local plasmid delivery, and stimulates significantly more weight gain than delivery of the naked plasmid alone.

  8. Bifunctional heterometallic Ln3+-Gd3+ (Ln = Eu, Tb) hybrid silica microspheres: luminescence and MRI contrast agent property.

    PubMed

    Li, Yan-Yan; Yan, Bing; Li, Qiu-Ping

    2013-02-01

    A novel series of homometallic and heterometallic lanthanide (Eu(3+)(Tb(3+))-Gd(3+)) hybrid silica microspheres (EDTA-(Eu(Tb)-Gd)-TTA-SiO(2)) are synthesized with 2-thenoyltrifluoroacetone (TTA) functionalized silane and ethylenediaminetetraacetic acid (EDTA) by sol-gel process, whose physical characterization are carried out and especially the luminescence and the magnetic resonance imaging (MRI) contrast agent properties are discussed. These hybrids present uniform silica microsphere morphology with particle size of 1 μm. Comparing to the homometallic hybrid silica microsphere EDTA-Ln-TTA-SiO(2) without Gd(3+) ion, the heterometallic hybrid silica microspheres EDTA-Eu-Gd-TTA-SiO(2) exhibit stronger luminescent intensity, longer lifetime and higher luminescent quantum efficiency, which is due to the fact that inert ion Gd(3+) can enhance the luminescence of the Eu(3+) or Tb(3+) within the hybrid system. In addition, the MRI relaxivity of the heterometallic lanthanide hybrid silica microspheres in water is assessed, showing a lower T1 relaxation rate than homometallic gadolinium hybrid one (EDTA-Gd-TTA-SiO(2)). Both of them show higher T1 relaxation rate than the conventional Gd chelate of diethylenetriamine pentaacetic acid. These bifunctional hybrid materials exhibit both luminescent and MRI magnetic contrast agent properties, whose further investigation can be expected to have potential application in practical fields such as optical storage and sensors, etc. PMID:23154785

  9. Computational dynamics of acoustically driven microsphere systems.

    PubMed

    Glosser, Connor; Piermarocchi, Carlo; Li, Jie; Dault, Dan; Shanker, B

    2016-01-01

    We propose a computational framework for the self-consistent dynamics of a microsphere system driven by a pulsed acoustic field in an ideal fluid. Our framework combines a molecular dynamics integrator describing the dynamics of the microsphere system with a time-dependent integral equation solver for the acoustic field that makes use of fields represented as surface expansions in spherical harmonic basis functions. The presented approach allows us to describe the interparticle interaction induced by the field as well as the dynamics of trapping in counter-propagating acoustic pulses. The integral equation formulation leads to equations of motion for the microspheres describing the effect of nondissipative drag forces. We show (1) that the field-induced interactions between the microspheres give rise to effective dipolar interactions, with effective dipoles defined by their velocities and (2) that the dominant effect of an ultrasound pulse through a cloud of microspheres gives rise mainly to a translation of the system, though we also observe both expansion and contraction of the cloud determined by the initial system geometry. PMID:26871188

  10. Dosimetry of in situ activated dysprosium microspheres.

    PubMed

    Adnani, N

    2004-03-01

    This paper presents the results of a study aimed at investigating the dosimetry of stable dysprosium microspheres activated, in situ, by a linac generated photon beam. In phantom measurements of the neutron flux within an 18 MV photon beam were performed using CR-39 detectors and gold activation. The results were used in conjunction with a Monte Carlo computer simulation to investigate the dose distribution resulting from the activation of dysprosium (Dy) microspheres using an 18 MV photon beam. Different depths, lesion volumes and volume concentrations of microspheres are investigated. The linac lower collimator jaws are assumed completely closed to shield the tumour volume from the photon dose. Using a single AP field with 0 x 0 cm2 field size (closed jaws), a photon dose rate of 600 MU min(-1) and 80 cm SSD for 10 min, an average dose exceeding 1 Gy can be delivered to spherical lesions of 0.5 cm and higher diameter. The variation of the average dose with the size of the lesion reaches saturation for tumour volumes exceeding 1 cm in diameter. This report shows that the photon beam of a high-energy linac can be used to activate Dy microspheres in situ and, as a result, deliver a significant dose of beta radiation. Non-radioactive Dy microspheres do not have the toxicity and imaging problems associated with commercially available yttrium-90 based products. PMID:15070199

  11. Computational dynamics of acoustically driven microsphere systems.

    PubMed

    Glosser, Connor; Piermarocchi, Carlo; Li, Jie; Dault, Dan; Shanker, B

    2016-01-01

    We propose a computational framework for the self-consistent dynamics of a microsphere system driven by a pulsed acoustic field in an ideal fluid. Our framework combines a molecular dynamics integrator describing the dynamics of the microsphere system with a time-dependent integral equation solver for the acoustic field that makes use of fields represented as surface expansions in spherical harmonic basis functions. The presented approach allows us to describe the interparticle interaction induced by the field as well as the dynamics of trapping in counter-propagating acoustic pulses. The integral equation formulation leads to equations of motion for the microspheres describing the effect of nondissipative drag forces. We show (1) that the field-induced interactions between the microspheres give rise to effective dipolar interactions, with effective dipoles defined by their velocities and (2) that the dominant effect of an ultrasound pulse through a cloud of microspheres gives rise mainly to a translation of the system, though we also observe both expansion and contraction of the cloud determined by the initial system geometry.

  12. Preparation of grafted microspheres CPVA-g-PSSS and studies on their drug-carrying and colon-specific drug delivery properties.

    PubMed

    Gao, Baojiao; Fang, Li; Men, Jiying; Zhang, Yanyan

    2013-04-01

    Sodium 4-styrene sulfonate (SSS) was graft-polymerized on the surfaces of crosslinked polyvinyl alcohol (CPVA) microspheres in a manner of surface-initiated graft-polymerization by using cerium salt-hydroxyl group redox initiation system, obtaining the grafted microspheres CPVA-g-PSSS. The chemical structure and physicochemical characters of CPVA-g-PSSS microspheres were fully characterized with infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and zeta potential determination. The aim of this work is to constitute a novel colon-specific drug delivery system via molecular design by using CPVA-g-PSSS microspheres as the drug-carrying material and by taking metronidazole (MTZ) as the model drug. The drug-carrying ability and mechanism of the grafted microspheres CPVA-g-PSSS for MTZ were investigated. Finally, in-vitro release tests for the drug-carrying microspheres were conducted. The experimental results show that in an acidic medium, the grafted microspheres CPVA-g-PSSS exhibit strong adsorption ability for MTZ by driving of electrostatic interaction, and have an adsorption capacity of 112 mg/g, displaying the high efficiency of drug-carrying. The in-vitro release behavior of the drug-carried microspheres is highly pH-sensitive. In the medium of pH=1, the drug-carrying microspheres do not release the drug, whereas in the medium of pH=7.4, a sudden delivery phenomenon of the drug will occur, displaying an excellent colon-specific drug delivery behavior.

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

    PubMed

    Selek, H; Sahin, S; Ercan, M T; Sargon, M; Hincal, A A; Kas, H S

    2003-01-01

    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. PMID:12554379

  14. Application of Raman microscopy to biodegradable double-walled microspheres.

    PubMed

    Widjaja, Effendi; Lee, Wei Li; Loo, Say Chye Joachim

    2010-02-15

    Raman mapping measurements were performed on the cross section of the ternary-phase biodegradable double-walled microsphere (DWMS) of poly(D,L-lactide-co-glycolide) (50:50) (PLGA), poly(L-lactide) (PLLA), and poly(epsilon-caprolactone) (PCL), which was fabricated by a one-step solvent evaporation method. The collected Raman spectra were subjected to a band-target entropy minimization (BTEM) algorithm in order to reconstruct the pure component spectra of the species observed in this sample. Seven pure component spectral estimates were recovered, and their spatial distributions within DWMS were determined. The first three spectral estimates were identified as PLLA, PLGA 50:50, and PCL, which were the main components in DWMS. The last four spectral estimates were identified as semicrystalline polyglycolic acid (PGA), dichloromethane (DCM), copper-phthalocyanine blue, and calcite, which were the minor components in DWMS. PGA was the decomposition product of PLGA. DCM was the solvent used in DWMS fabrication. Copper-phthalocyanine blue and calcite were the unexpected contaminants. The current result showed that combined Raman microscopy and BTEM analysis can provide a sensitive characterization tool to DWMS, as it can give more specific information on the chemical species present as well as the spatial distributions. This novel analytical method for microsphere characterization can serve as a complementary tool to other more established analytical techniques, such as scanning electron microscopy and optical microscopy.

  15. Mechanism of immunoglobulin G adsorption on polystyrene microspheres.

    PubMed

    Sofińska, Kamila; Adamczyk, Zbigniew; Barbasz, Jakub

    2016-01-01

    The adsorption of polyclonal immunoglobulin G (IgG) on negatively charged polystyrene microparticle suspension (latex) was studied by using the Laser Doppler Velocimetry (LDV) measurements. Using this technique, the dependence of the electrophoretic mobility of particles on the IgG concentration in the suspension was measured for various ionic strengths and pH 3.5. The increase in the electrophoretic mobility was quantitatively interpreted in terms of the 3D electrokinetic model. On the other hand, the maximum coverage of IgG on latex was determined using the depletion method based on AFM imaging. It was shown that IgG adsorption was irreversible and that its maximum coverage on the microspheres increased from 1.4mgm(-2) for 0.001M NaCl to 2.0mgm(-2) for 0.15M NaCl. This was interpreted in terms of reduced electrostatic repulsion among adsorbed molecules. The stability of IgG monolayers on the particles was confirmed in separate experiments where changes in its electrophoretic mobility were monitored over prolonged time periods. Additionally, the acid-base properties of the IgG monolayers on latex were determined in pH cycling experiments. The isoelectric point of the IgG monolayers on the microspheres was 4.8. The results obtained in this work indicate that basic physicochemical characteristics of IgG can be acquired via electrophoretic mobility measurements using microgram quantities of the protein.

  16. Localized drugs delivery hydroxyapatite microspheres for osteoporosis therapy

    NASA Astrophysics Data System (ADS)

    Lee, J. H.; Ko, I. H.; Jeon, S.-H.; Chae, J. H.; Lee, E. J.; Chang, J. H.

    2011-10-01

    This study describes the preparation of hydroxyapatite microspheres for local drugs delivery. The formation of the hydroxyapatite microspheres was initiated by enzymatic decomposition of urea and accomplished by emulsification process (water-in-oil). The microspheres obtained were sintered at 500°C. Scanning electron microscope (SEM) indicated that the microspheres have various porous with random size, which maximizes the surface area. Cytotoxicity was not observed after sintering. Osteoporosis drugs, alendronate and BMP-2, were loaded into HAp microspheres and the releases of both molecules showed sustained releasing profiles.

  17. Acrolein Microspheres Are Bonded To Large-Area Substrates

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan; Yen, Richard C. K.

    1988-01-01

    Reactive cross-linked microspheres produced under influence of ionizing radiation in aqueous solutions of unsaturated aldehydes, such as acrolein, with sodium dodecyl sulfate. Diameters of spheres depend on concentrations of ingredients. If polystyrene, polymethylmethacrylate, or polypropylene object immersed in solution during irradiation, microspheres become attached to surface. Resulting modified surface has grainy coating with reactivity similar to free microspheres. Aldehyde-substituted-functional microspheres react under mild conditions with number of organic reagents and with most proteins. Microsphere-coated macrospheres or films used to immobilize high concentrations of proteins, enzymes, hormones, viruses, cells, and large number of organic compounds. Applications include separation techniques, clinical diagnostic tests, catalytic processes, and battery separators.

  18. Preparation and in vitro evaluation of xanthan gum facilitated superabsorbent polymeric microspheres.

    PubMed

    Bhattacharya, Shiv Sankar; Mazahir, Farhan; Banerjee, Subham; Verma, Anurag; Ghosh, Amitava

    2013-10-15

    Interpenetrating polymer network (IPN) hydrogel microspheres of xanthan gum (XG) based superabsorbent polymer (SAP) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for sustained release of ciprofloxacin hydrochloride (CIPRO). The microspheres were prepared with various ratios of hydrolyzed SAP to PVA and extent of crosslinking density. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acidic and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results, this study suggest that CIPRO loaded IPN microspheres were suitable for sustained release application. PMID:23987317

  19. Cold Atmospheric Plasma Modified Electrospun Scaffolds with Embedded Microspheres for Improved Cartilage Regeneration

    PubMed Central

    Zhu, Wei; Castro, Nathan J.; Cheng, Xiaoqian; Keidar, Michael; Zhang, Lijie Grace

    2015-01-01

    Articular cartilage is prone to degeneration and possesses extremely poor self-healing capacity due to inherent low cell density and the absence of a vasculature network. Tissue engineered cartilage scaffolds show promise for cartilage repair. However, there still remains a lack of ideal biomimetic tissue scaffolds which effectively stimulate cartilage regeneration with appropriate functional properties. Therefore, the objective of this study is to develop a novel biomimetic and bioactive electrospun cartilage substitute by integrating cold atmospheric plasma (CAP) treatment with sustained growth factor delivery microspheres. Specifically, CAP was applied to a poly(ε-caprolactone) electrospun scaffold with homogeneously distributed bioactive factors (transforming growth factor-β1 and bovine serum albumin) loaded poly(lactic-co-glycolic) acid microspheres. We have shown that CAP treatment renders electrospun scaffolds more hydrophilic thus facilitating vitronectin adsorption. More importantly, our results demonstrate, for the first time, CAP and microspheres can synergistically enhance stem cell growth as well as improve chondrogenic differentiation of human marrow-derived mesenchymal stem cells (such as increased glycosaminoglycan, type II collagen, and total collagen production). Furthermore, CAP can substantially enhance 3D cell infiltration (over two-fold increase in infiltration depth after 1 day of culture) in the scaffolds. By integrating CAP, sustained bioactive factor loaded microspheres, and electrospinning, we have fabricated a promising bioactive scaffold for cartilage regeneration. PMID:26222527

  20. Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells.

    PubMed

    Kuang, Rong; Zhang, Zhanpeng; Jin, Xiaobing; Hu, Jiang; Gupte, Melanie J; Ni, Longxing; Ma, Peter X

    2015-09-16

    Dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF-SMS), is developed for dentin regeneration. Biodegradable and biocompatible poly(l-lactic acid)-block-poly(l-lysine) are synthesized and fabricated into NF-SMS using self-assembly and thermally induced phase separation techniques. It is hypothesized that NF-SMS with interconnected pores and nanofibers can enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF-MS) without pore structure and conventional solid microspheres (S-MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferate significantly faster on NF-SMS than on NF-MS or S-MS (p < 0.05). Following in vitro odontogenic induction, all the examined odontogenic genes (alkaline phosphatase content, osteocalcin, bone sialoprotein, collagen 1, dentin sialophosphoprotein (DSPP)), calcium content, and DSPP protein content are found significantly higher in the NF-SMS group than in the control groups. Furthermore, 6 weeks after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis shows that NF-SMS support superior dentin-like tissue formation compared to NF-MS or S-MS. Taken together, NF-SMS have great potential as an injectable cell carrier for dentin regeneration.

  1. A method to tune the shape of protein-encapsulated polymeric microspheres

    NASA Astrophysics Data System (ADS)

    Alteriis, Renato De; Vecchione, Raffaele; Attanasio, Chiara; Gregorio, Maria De; Porzio, Massimiliano; Battista, Edmondo; Netti, Paolo A.

    2015-07-01

    Protein encapsulation technologies of polymeric microspheres currently in use have been optimized to effectively protect their “protein cargo” from inactivation occurring in biological environments, preserving its bioactivity during release up to several weeks. The scenario of protein delivery would greatly benefit by strategies enabling the production of non-spherical particles. Herein we report an easy and effective stamp-based method to produce poly-lactic-glycolic-acid (PLGA) microparticles encapsulating Vascular Endothelial Growth Factor (VEGF) of different shapes. We demonstrate that PLGA microspheres can be deformed at room temperature exploiting solvent/non-solvent plasticization in order to preserve the properties of the starting microspheres. This gentle method allows the production of shaped particles that provide a prolonged release of VEGF in active form, as verified by an angiogenic assay. The retention of the biological activity of an extremely labile molecule, i.e. VEGF, lets us hypothesize that a wide variety of drug and protein encapsulated polymeric microspheres can be processed using this method.

  2. Selective adsorption and separation of organic dyes from aqueous solution on polydopamine microspheres.

    PubMed

    Fu, Jianwei; Xin, Qianqian; Wu, Xuechen; Chen, Zhonghui; Yan, Ya; Liu, Shujun; Wang, Minghuan; Xu, Qun

    2016-01-01

    Polydopamine (PDA) microspheres, synthesized by a facile oxidation polymerization route, were evaluated as a potential adsorbent for selective adsorption and separation of organic dyes. The adsorption processes towards nine water-soluble dyes (anionic dyes: methyl orange (MO), eosin-Y (EY), eosin-B (EB), acid chrome blue K (ACBK), neutral dye: neutral red (NR), and cationic dyes: rhodamine B (RhB), malachite green (MG), methylene blue (MB), safranine T (ST)) were thoroughly investigated. The adsorption selectivity of organic dyes onto PDA microspheres was successfully applied for the separation of dyes mixtures. Various influential factors such as solution pH, temperature, and contact time were employed to ascertain the optimal condition for adsorption of representative organic dyes including MB, MG and NR. The pseudo-first-order and pseudo-second-order kinetics models were used to fit the adsorption kinetics process. Five isothermal adsorption models (Langmuir, Dubnin-Radushkevich, Temkin, Freundlich and Harkins-Jura) were used to investigate the adsorption thermodynamics properties. The results showed that the PDA microspheres owned good selective adsorption ability towards cationic dyes. The adsorption kinetics process conformed to the pseudo-second-order kinetics model and the Langmuir isotherm model was more appropriate for tracing the adsorption behavior than other isotherm models. Thus, we can conclude PDA microspheres may be a high-efficiency selective adsorbent towards some cationic dyes.

  3. Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells.

    PubMed

    Kuang, Rong; Zhang, Zhanpeng; Jin, Xiaobing; Hu, Jiang; Gupte, Melanie J; Ni, Longxing; Ma, Peter X

    2015-09-16

    Dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF-SMS), is developed for dentin regeneration. Biodegradable and biocompatible poly(l-lactic acid)-block-poly(l-lysine) are synthesized and fabricated into NF-SMS using self-assembly and thermally induced phase separation techniques. It is hypothesized that NF-SMS with interconnected pores and nanofibers can enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF-MS) without pore structure and conventional solid microspheres (S-MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferate significantly faster on NF-SMS than on NF-MS or S-MS (p < 0.05). Following in vitro odontogenic induction, all the examined odontogenic genes (alkaline phosphatase content, osteocalcin, bone sialoprotein, collagen 1, dentin sialophosphoprotein (DSPP)), calcium content, and DSPP protein content are found significantly higher in the NF-SMS group than in the control groups. Furthermore, 6 weeks after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis shows that NF-SMS support superior dentin-like tissue formation compared to NF-MS or S-MS. Taken together, NF-SMS have great potential as an injectable cell carrier for dentin regeneration. PMID:26138254

  4. PLGA-Listeriolysin O microspheres: Opening the gate for cytosolic delivery of cancer antigens.

    PubMed

    Gilert, Ariel; Baruch, Limor; Bronshtein, Tomer; Machluf, Marcelle

    2016-04-01

    Strategies for cancer protein vaccination largely aim to activate the cellular arm of the immune system against cancer cells. This approach, however, is limited since protein vaccines mostly activate the system's humoral arm instead. One way to overcome this problem is to enhance the cross-presentation of such proteins by antigen-presenting cells, which may consequently lead to intense cellular response. Here we examined the ability of listeriolysin O (LLO) incorporated into poly-lactic-co-glycolic acid (PLGA) microspheres to modify the cytosolic delivery of low molecular weight peptides and enhance their cross-presentation. PLGA microspheres were produced in a size suitable for uptake by phagocytic cells. The peptide encapsulation and release kinetics were improved by adding NaCl to the preparation. PLGA microspheres loaded with the antigenic peptide and incorporated with LLO were readily up-taken by phagocytic cells, which exhibited an increase in the expression of peptide-MHC-CI complexes on the cell surface. Furthermore, this system enhanced the activation of a specific T hybridoma cell line, thus simulating cytotoxic T cells. These results establish, for the first time, a proof of concept for the use of PLGA microspheres incorporated with a pore-forming agent and the antigen peptide of choice as a unique cancer protein vaccination delivery platform.

  5. Cold Atmospheric Plasma Modified Electrospun Scaffolds with Embedded Microspheres for Improved Cartilage Regeneration.

    PubMed

    Zhu, Wei; Castro, Nathan J; Cheng, Xiaoqian; Keidar, Michael; Zhang, Lijie Grace

    2015-01-01

    Articular cartilage is prone to degeneration and possesses extremely poor self-healing capacity due to inherent low cell density and the absence of a vasculature network. Tissue engineered cartilage scaffolds show promise for cartilage repair. However, there still remains a lack of ideal biomimetic tissue scaffolds which effectively stimulate cartilage regeneration with appropriate functional properties. Therefore, the objective of this study is to develop a novel biomimetic and bioactive electrospun cartilage substitute by integrating cold atmospheric plasma (CAP) treatment with sustained growth factor delivery microspheres. Specifically, CAP was applied to a poly(ε-caprolactone) electrospun scaffold with homogeneously distributed bioactive factors (transforming growth factor-β1 and bovine serum albumin) loaded poly(lactic-co-glycolic) acid microspheres. We have shown that CAP treatment renders electrospun scaffolds more hydrophilic thus facilitating vitronectin adsorption. More importantly, our results demonstrate, for the first time, CAP and microspheres can synergistically enhance stem cell growth as well as improve chondrogenic differentiation of human marrow-derived mesenchymal stem cells (such as increased glycosaminoglycan, type II collagen, and total collagen production). Furthermore, CAP can substantially enhance 3D cell infiltration (over two-fold increase in infiltration depth after 1 day of culture) in the scaffolds. By integrating CAP, sustained bioactive factor loaded microspheres, and electrospinning, we have fabricated a promising bioactive scaffold for cartilage regeneration. PMID:26222527

  6. Spherical and polygonal shape of Au nanoparticles coated functionalized polymer microspheres

    NASA Astrophysics Data System (ADS)

    Xu, Ting; Li, Yingzhi; Zhang, Junxian; Qi, Yalong; Zhao, Xin; Zhang, Qinghua

    2015-08-01

    Uniform polystyrene (PS)/polypyrrole (PPy) composite microspheres with well-defined core/shell structures are synthesized by chemical oxidative polymerization. Gold nanoparticles (Au NPs) are successfully coated on the surface of PS/PPy microspheres by means of electrostatic interactions due to the functionalized PPy coatings supplying sufficient amino groups and the additive of mercapto acetic acid. Furthermore, the as-prepared PS/PPy/Au microspheres serving as seeds facilitate Au NPs further growth by in situ reduction in HAuCl4 solution to obtain PS/PPy/Au spheres with the core/shell/shell structure. Morphology observation demonstrates that the monodisperse PS/PPy/Au microspheres compose of uniform cores and the compact coatings containing distinct two layers. X-ray diffraction and X-ray photoelectron spectroscope confirm the existence of PPy and Au on the surface of the composite spheres. This facile approach to preparing metal-coated polymer spheres supplies the potential applications in biosensors, electronics and medical diagnosis.

  7. Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

    NASA Astrophysics Data System (ADS)

    Zhou, Hui-Yun; Cao, Pei-Pei; Zhao, Jie; Wang, Zhi-Ying; Li, Jun-Bo; Zhang, Fa-Liang

    2014-12-01

    Novel ethyl cellulose/chitosan microspheres (ECCMs) were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 μm. The drug loading efficiency of berberine hydrochloride (BH) loaded in microspheres were affected by chitosan (CS) concentration, EC concentration and the volume ratio of V(CS)/ V(EC). ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid (dHCl) and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCl and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.

  8. Validation of fluorescent-labeled microspheres for measurement of relative blood flow in severely injured lungs

    NASA Technical Reports Server (NTRS)

    Hubler, M.; Souders, J. E.; Shade, E. D.; Hlastala, M. P.; Polissar, N. L.; Glenny, R. W.

    1999-01-01

    The aim of the study was to validate a nonradioactive method for relative blood flow measurements in severely injured lungs that avoids labor-intensive tissue processing. The use of fluorescent-labeled microspheres was compared with the standard radiolabeled-microsphere method. In seven sheep, lung injury was established by using oleic acid. Five pairs of radio- and fluorescent-labeled microspheres were injected before and after established lung injury. Across all animals, 175 pieces were selected randomly. The radioactivity of each piece was determined by using a scintillation counter. The fluorescent dye was extracted from each piece with a solvent without digestion or filtering. The fluorescence was determined with an automated fluorescent spectrophotometer. Perfusion was calculated for each piece from both the radioactivity and fluorescence and volume normalized. Correlations between flow determined by the two methods were in the range from 0.987 +/- 0.007 (SD) to 0.991 +/- 0.002 (SD) after 9 days of soaking. Thus the fluorescent microsphere technique is a valuable tool for investigating regional perfusion in severely injured lungs and can replace radioactivity.

  9. Preparation and in vitro evaluation of xanthan gum facilitated superabsorbent polymeric microspheres.

    PubMed

    Bhattacharya, Shiv Sankar; Mazahir, Farhan; Banerjee, Subham; Verma, Anurag; Ghosh, Amitava

    2013-10-15

    Interpenetrating polymer network (IPN) hydrogel microspheres of xanthan gum (XG) based superabsorbent polymer (SAP) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for sustained release of ciprofloxacin hydrochloride (CIPRO). The microspheres were prepared with various ratios of hydrolyzed SAP to PVA and extent of crosslinking density. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acidic and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results, this study suggest that CIPRO loaded IPN microspheres were suitable for sustained release application.

  10. Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutine.

    PubMed

    Hashimoto, Yoshimi; Tanaka, Masami; Kishimoto, Hideyuki; Shiozawa, Hiroyoshi; Hasegawa, Kazumasa; Matsuyama, Kenji; Uchida, Takahiro

    2002-10-01

    The objectives of this study were to produce acid soluble, polyvinylacetal diethylaminoacetate (AEA) microspheres containing trimebutine (as maleate), using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation method, to characterize their in-vitro release properties, and to evaluate the taste-masking potential of this formulation in human volunteers. The pH of the external aqueous phase was the critical factor in achieving a high loading efficiency for trimebutine in the microencapsulation process; nearly 90% (w/w) loading efficiency was obtained at above pH 10. Trimebutine was completely released from AEA microspheres within 10 min in a dissolution test at pH 1.2, simulating conditions in the stomach, whereas at pH 6.8, the pH in the mouth, only small quantities of trimebutine were released in the initial 1-2 min. The results of a gustatory sensation test in healthy volunteers confirmed the taste-masking effects of the AEA microspheres. Finally, an attempt was made to encapsulate the salts of other basic drugs (lidocaine, imipramine, desipramine, amitriptyline, promethazine and chlorpheniramine) into AEA microspheres using the w/o/w emulsion evaporation method. The loading efficiencies were ranked in almost inverse proportion with the solubility of the drugs in the external aqueous phase. This study demonstrated the possibility of masking the taste of salts of basic drugs by microencapsulation with AEA using a w/o/w emulsion solvent evaporation method. PMID:12396292

  11. Selective adsorption and separation of organic dyes from aqueous solution on polydopamine microspheres.

    PubMed

    Fu, Jianwei; Xin, Qianqian; Wu, Xuechen; Chen, Zhonghui; Yan, Ya; Liu, Shujun; Wang, Minghuan; Xu, Qun

    2016-01-01

    Polydopamine (PDA) microspheres, synthesized by a facile oxidation polymerization route, were evaluated as a potential adsorbent for selective adsorption and separation of organic dyes. The adsorption processes towards nine water-soluble dyes (anionic dyes: methyl orange (MO), eosin-Y (EY), eosin-B (EB), acid chrome blue K (ACBK), neutral dye: neutral red (NR), and cationic dyes: rhodamine B (RhB), malachite green (MG), methylene blue (MB), safranine T (ST)) were thoroughly investigated. The adsorption selectivity of organic dyes onto PDA microspheres was successfully applied for the separation of dyes mixtures. Various influential factors such as solution pH, temperature, and contact time were employed to ascertain the optimal condition for adsorption of representative organic dyes including MB, MG and NR. The pseudo-first-order and pseudo-second-order kinetics models were used to fit the adsorption kinetics process. Five isothermal adsorption models (Langmuir, Dubnin-Radushkevich, Temkin, Freundlich and Harkins-Jura) were used to investigate the adsorption thermodynamics properties. The results showed that the PDA microspheres owned good selective adsorption ability towards cationic dyes. The adsorption kinetics process conformed to the pseudo-second-order kinetics model and the Langmuir isotherm model was more appropriate for tracing the adsorption behavior than other isotherm models. Thus, we can conclude PDA microspheres may be a high-efficiency selective adsorbent towards some cationic dyes. PMID:26407057

  12. PLGA microsphere-mediated growth hormone release hormone expression induces intergenerational growth.

    PubMed

    Ren, Xiao-Hui; Zhang, Yong-Liang; Luo, Hu-Ying; Li, Hong-Yi; Liu, Song-Cai; Zhang, Ming-Jun; Ouyang, Song-Ying; Xi, Qian-Yun; Jiang, Qing-Yan

    2009-01-01

    To improve animal growth, growth hormone-releasing hormone (GHRH) expression vectors that maintain constant GHRH expression can be directly injected into muscles. To deliver the GHRH expression vectors, biodegradable microspheres have been used as a sustained release system. Although administering GHRH through microspheres is a common practice, the intergenerational effects of this delivery system are unknown. To investigate the intergenerational effects of polylactic-co-glycolic acid (PLGA) encapsulated plasmid-mediated GHRH supplements, pCMV-Rep-GHRH microspheres were injected into pregnant mice. Growth and expression of GHRH were measured in the offspring. RT-PCR and immunohistochemistry reveal GHRH expression 3-21 days post-injection. The proportion of GH-positive cells in the GHRH treated offspring was 48.2% higher than in the control group (P < 0.01). The GHRH treated offspring were 6.15% (P < 0.05) larger than the control offspring. At day 49 post-injection, IGF-I serum levels were significantly higher in the treatment group than in the control group. This study confirms that intramuscular expression of GHRH mediated by PLGA microspheres significantly enhances intergenerational growth.

  13. An enzymatic immunoassay microfluidics integrated with membrane valves for microsphere retention and reagent mixing.

    PubMed

    Ren, Li; Wang, Jian-Chun; Liu, Wenming; Tu, Qin; Liu, Rui; Wang, Xueqin; Xu, Juan; Wang, Yaolei; Zhang, Yanrong; Li, Li; Wang, Jinyi

    2012-05-15

    The present study presents a new microfluidic device integrated with pneumatic microvalves and a membrane mixer for enzyme-based immunoassay of acute myocardial infarction (AMI) biomarkers, namely, myoglobin, and heart-type fatty acid binding protein (H-FABP). Superparamagnetic microspheres with carboxyl groups on their surfaces were used as antibody solid carriers. A membrane mixer consisting of four ψ-type membrane valves was assembled under the reaction chamber for on-chip performing microsphere trapping and reagent mixing. The entire immunoassay process, including microsphere capture, reagent input, mixing, and subsequent reaction, was accomplished on the device either automatically or manually. The post-reaction substrate resultant was analyzed using a microplate reader. The results show that the average absorbance value is correlated with the concentration of cardiac markers, in agreement with the results obtained using a conventional microsphere-based immunoassay; this indicated that the proposed on-chip immunoassay protocol could be used to detect both myoglobin and H-FABP. The minimum detectable concentration is 5 ng/mL for myoglobin and 1 ng/mL for H-FABP.

  14. Biosensing by WGM Microspherical Resonators

    PubMed Central

    Righini, Giancarlo C.; Soria, Silvia

    2016-01-01

    Whispering gallery mode (WGM) microresonators, thanks to their unique properties, have allowed researchers to achieve important results in both fundamental research and engineering applications. Among the various geometries, microspheres are the simplest 3D WGM resonators; the total optical loss in such resonators can be extremely low, and the resulting extraordinarily high Q values of 108–109 lead to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. They can also be coated in order to better control their properties or to increase their functionality. Their very high sensitivity to changes in the surrounding medium has been exploited for several sensing applications: protein adsorption, trace gas detection, impurity detection in liquids, structural health monitoring of composite materials, detection of electric fields, pressure sensing, and so on. In the present paper, after a general introduction to WGM resonators, attention is focused on spherical microresonators, either in bulk or in bubble format, to their fabrication, characterization and functionalization. The state of the art in the area of biosensing is presented, and the perspectives of further developments are discussed. PMID:27322282

  15. Biosensing by WGM Microspherical Resonators.

    PubMed

    Righini, Giancarlo C; Soria, Silvia

    2016-01-01

    Whispering gallery mode (WGM) microresonators, thanks to their unique properties, have allowed researchers to achieve important results in both fundamental research and engineering applications. Among the various geometries, microspheres are the simplest 3D WGM resonators; the total optical loss in such resonators can be extremely low, and the resulting extraordinarily high Q values of 10⁸-10⁸ lead to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. They can also be coated in order to better control their properties or to increase their functionality. Their very high sensitivity to changes in the surrounding medium has been exploited for several sensing applications: protein adsorption, trace gas detection, impurity detection in liquids, structural health monitoring of composite materials, detection of electric fields, pressure sensing, and so on. In the present paper, after a general introduction to WGM resonators, attention is focused on spherical microresonators, either in bulk or in bubble format, to their fabrication, characterization and functionalization. The state of the art in the area of biosensing is presented, and the perspectives of further developments are discussed. PMID:27322282

  16. Biosensing by WGM Microspherical Resonators.

    PubMed

    Righini, Giancarlo C; Soria, Silvia

    2016-06-17

    Whispering gallery mode (WGM) microresonators, thanks to their unique properties, have allowed researchers to achieve important results in both fundamental research and engineering applications. Among the various geometries, microspheres are the simplest 3D WGM resonators; the total optical loss in such resonators can be extremely low, and the resulting extraordinarily high Q values of 10⁸-10⁸ lead to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. They can also be coated in order to better control their properties or to increase their functionality. Their very high sensitivity to changes in the surrounding medium has been exploited for several sensing applications: protein adsorption, trace gas detection, impurity detection in liquids, structural health monitoring of composite materials, detection of electric fields, pressure sensing, and so on. In the present paper, after a general introduction to WGM resonators, attention is focused on spherical microresonators, either in bulk or in bubble format, to their fabrication, characterization and functionalization. The state of the art in the area of biosensing is presented, and the perspectives of further developments are discussed.

  17. Sonochemical proteinaceous microspheres for wound healing.

    PubMed

    Silva, Raquel; Ferreira, Helena; Vasconcelos, Andreia; Gomes, Andreia C; Cavaco-Paulo, Artur

    2012-01-01

    In this work, we report a novel approach using proteinaceous microspheres of bovine serum albumin (BSA), human serum albumin (HSA) and silk fibroin (SF) containing different organic solvents, namely n-dodecane, mineral oil and vegetable oil, to reduce the activity of human neutrophil elastase (HNE) found in high levels on chronic wounds. The ability of these devices to inhibit HNE was evaluated using porcine pancreatic elastase (PPE) solution as a model of wound exudates. The results obtained indicated that the level of PPE activity can be tuned by changing the organic solvent present on different protein microspheres, thus showing an innovative way of controlling the elastase-antielastase imbalance found in chronic wounds. Furthermore, these proteinaceous microspheres were shown to be important carriers of elastase inhibitors causing no cytotoxicity in human skin fibroblasts in vitro, making them suitable for biomedical applications, such as chronic wounds.

  18. Flow-through ultrasonic emulsification combined with static micromixing for aseptic production of microspheres by solvent extraction.

    PubMed

    Freitas, Sergio; Rudolf, Beat; Merkle, Hans P; Gander, Bruno

    2005-10-01

    Final sterilisation of drug-loaded polymeric microspheres is problematic as dry heat or steam sterilisation are not applicable, and gamma-irradiation may result in radiolytic scission of the polymer chains, and potentially damage the bioactive compound. Therefore, aseptic production is the method of choice to obtain a sterile product. A novel process for the production of microspheres is introduced based on the principle of double emulsion-solvent extraction. The process uses a flow-through ultrasonic cell for the preparation of the primary emulsion, in combination with a static micromixer for the production of the double emulsion. Because of its small scale, the equipment is readily accommodated in a laminar air-flow cabinet or an isolator. Thanks to the low technical complexity and easy handling of the process, only minimal manual interventions is required. Finally, the possibility for in-place cleaning and sterilisation makes the equipment and process well suited for aseptic microsphere preparation. Microspheres were prepared from poly(lactic-co-glycolic acid) (PLGA), and bovine serum albumin (BSA) served as model protein for microencapsulation. The BSA-in-PLGA (w/o) emulsions produced by the ultrasonic flow-through cell exhibited mean droplet sizes of <700 nm. Further processing into microspheres of 15-40 microm mean diameter resulted in approx. 70% BSA encapsulation efficiency. Batch-to-batch reproducibility was excellent. Microsphere batches produced under aseptic conditions to assure product sterility exhibited no microbial contamination when examined by a simplified sterility test. The presented technology offers great potential for aseptic microsphere production for batch-sizes suitable, e.g. for clinical investigations. Complete validation of product sterility would, however, demand more extended tests. PMID:16009542

  19. Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach.

    PubMed

    Gu, Bing; Burgess, Diane J

    2015-11-10

    Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25 kDa) and PLGA9010 (113 kDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration.

  20. Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach.

    PubMed

    Gu, Bing; Burgess, Diane J

    2015-11-10

    Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25 kDa) and PLGA9010 (113 kDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration. PMID:26325309

  1. Redox-responsive alginate microsphere containing cystamine.

    PubMed

    Kwon, Kyeongnan; Kim, Jin-Chul

    2016-10-01

    Redox-responsive microspheres were prepared by solidifying the alginate- and cystamine-containing water droplets of O/W emulsion using calcium ion. Emulsions were prepared using alginate/cystamine mixture solution whose the carboxylic group/the amino group molar ratio was 1:1, 1:2, and 1:3, and whose the total concentration was kept to 2% (w/v). The microspheres on Scanning electron microscopy photographs were almost spherical and they were less than 1 μm in diameter. According to the energy-dispersive X-ray spectroscopy, the sulfur content of the microspheres was found to be 6.1, 11.4, and 14.8% (w/w), respectively, not markedly different from the calculated content. The release degree of blue dextran loaded in the microspheres was higher as the cystamine content was higher. Microspheres released almost the same amount of dye regardless of dithiothreitol (DTT, a reducing agent) concentration when the cystamine content was relatively low (e.g. 14.5% (w/w)), whereas they released dye in DTT concentration-dependent manner when the cystamine content was relatively high (e.g. 27.0 and 35.1% (w/w)). The light scattering intensity of alginate/cystamine mixture solution was stronger at a larger amount of cystamine, indicating that cystamine could cross-link alginate chains. The light scattering intensity decreased with increasing DTT concentration, possibly because of the breakdown of the disulfide bond of cystamine. The breakdown of the disulfide bond could account for why the DTT concentration-dependent release of dye loaded in the microspheres was observed. PMID:27484719

  2. Enhanced visible-light-driven photocatalytic H2-production activity of CdS-loaded TiO2 microspheres with exposed (001) facets

    NASA Astrophysics Data System (ADS)

    Gao, Bifen; Yuan, Xia; Lu, Penghui; Lin, Bizhou; Chen, Yilin

    2015-12-01

    CdS-loaded TiO2 microspheres with highly exposed (001) facets were prepared by hydrothermal treatment of a TiF4-HCl-H2O mixed solution followed by a chemical bath deposition of CdS onto TiO2 microspheres. The crystal structure, surficial micro-structure and photo-absorption property of the samples were characterized by XRD, FE-SEM, TEM and UV-vis diffuse reflectance spectroscopy, etc. The as-prepared samples exhibited superior visible-light-driven photocatalytic H2-production activity from lactic acid aqueous solution in comparison with CdS-sensitized TiO2 nanoparticles, whose surface was dominated by (101) facets. Photoelectrochemical measurement confirmed that (001) facet is beneficial for the transfer of photo-generated electron from CdS to TiO2 microsphere, which led to the unexpected high photocatalytic activity of CdS-loaded TiO2 microspheres.

  3. Monodisperse α-Fe2O3 Mesoporous Microspheres: One-Step NaCl-Assisted Microwave-Solvothermal Preparation, Size Control and Photocatalytic Property

    NASA Astrophysics Data System (ADS)

    Cao, Shao-Wen; Zhu, Ying-Jie

    2011-12-01

    A simple one-step NaCl-assisted microwave-solvothermal method has been developed for the preparation of monodisperse α-Fe2O3 mesoporous microspheres. In this approach, Fe(NO3)3 · 9H2O is used as the iron source, and polyvinylpyrrolidone (PVP) acts as a surfactant in the presence of NaCl in mixed solvents of H2O and ethanol. Under the present experimental conditions, monodisperse α-Fe2O3 mesoporous microspheres can form via oriented attachment of α-Fe2O3 nanocrystals. One of the advantages of this method is that the size of α-Fe2O3 mesoporous microspheres can be adjusted in the range from ca. 170 to ca. 260 nm by changing the experimental parameters. High photocatalytic activities in the degradation of salicylic acid are observed for α-Fe2O3 mesoporous microspheres with different specific surface areas.

  4. Evaluation of protective efficacy using a nonstructural protein NS1 in DNA vaccine–loaded microspheres against dengue 2 virus

    PubMed Central

    Huang, Shih-Shiung; Li, I-Hsun; Hong, Po-da; Yeh, Ming-kung

    2013-01-01

    Dengue virus results in dengue fever or severe dengue hemorrhagic fever/dengue shock syndrome in humans. The purpose of this work was to develop an effective antidengue virus delivery system, by designing poly (dl-lactic-co-glycolic) acid/polyethylene glycol (PLGA/PEG) microspheres using a double-emulsion solvent extraction method, for vaccination therapy based on locally and continuously sustained biological activity. Nonstructural protein 1 (NS1) in deoxyribonucleic acid (DNA) vaccine–loaded PLGA/PEG microspheres exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (39%), the mean particle size 4.8 μm, and a controlled in vitro release profile with a low initial burst (18.5%), lag time (4 days), and continued released protein over 70 days. The distribution of protein on the microspheres surface, outer layer, and core were 3.0%, 28.5%, and 60.7%, respectively. A release rate was noticed to be 1.07 μg protein/mg microspheres/day of protein release, maintained for 42 days. The cumulative release amount at Days 1, 28, and 42 was 18.5, 53.7, and 62.66 μg protein/mg microspheres, respectively. The dengue virus challenge in mice test, in which mice received one dose of 20 μg NS1 protein content of microspheres, in comparison with NS1 protein in Al(OH)3 or PBS solution, was evaluated after intramuscular immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with NS1 protein–loaded PLGA/PEG microspheres (100%). In vivo vaccination studies also demonstrated that NS1 protein–loaded PLGA/PEG microspheres had a protective ability; its steady-state immune protection in rat plasma changed from 4,443 ± 1,384 pg/mL to 10,697 ± 3,197 pg/mL, which was 2.5-fold higher than that observed for dengue virus in Al(OH)3 at 21 days. These findings strongly suggest that NS1 protein–loaded PLGA/PEG microspheres offer a new therapeutic strategy in optimizing the vaccine

  5. Evaluation of protective efficacy using a nonstructural protein NS1 in DNA vaccine-loaded microspheres against dengue 2 virus.

    PubMed

    Huang, Shih-shiung; Li, I-Hsun; Hong, Po-da; Yeh, Ming-kung

    2013-01-01

    Dengue virus results in dengue fever or severe dengue hemorrhagic fever/dengue shock syndrome in humans. The purpose of this work was to develop an effective antidengue virus delivery system, by designing poly (dl-lactic-co-glycolic) acid/polyethylene glycol (PLGA/PEG) microspheres using a double-emulsion solvent extraction method, for vaccination therapy based on locally and continuously sustained biological activity. Nonstructural protein 1 (NS1) in deoxyribonucleic acid (DNA) vaccine-loaded PLGA/PEG microspheres exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (39%), the mean particle size 4.8 μm, and a controlled in vitro release profile with a low initial burst (18.5%), lag time (4 days), and continued released protein over 70 days. The distribution of protein on the microspheres surface, outer layer, and core were 3.0%, 28.5%, and 60.7%, respectively. A release rate was noticed to be 1.07 μg protein/mg microspheres/day of protein release, maintained for 42 days. The cumulative release amount at Days 1, 28, and 42 was 18.5, 53.7, and 62.66 μg protein/mg microspheres, respectively. The dengue virus challenge in mice test, in which mice received one dose of 20 μg NS1 protein content of microspheres, in comparison with NS1 protein in Al(OH)3 or PBS solution, was evaluated after intramuscular immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with NS1 protein-loaded PLGA/PEG microspheres (100%). In vivo vaccination studies also demonstrated that NS1 protein-loaded PLGA/PEG microspheres had a protective ability; its steady-state immune protection in rat plasma changed from 4,443 ± 1,384 pg/mL to 10,697 ± 3,197 pg/mL, which was 2.5-fold higher than that observed for dengue virus in Al(OH)3 at 21 days. These findings strongly suggest that NS1 protein-loaded PLGA/PEG microspheres offer a new therapeutic strategy in optimizing the vaccine incorporation

  6. Comparative study of LbL and crosslinked pH sensitive PEGylated LbL microspheres: synthesis, characterization and biological evaluation.

    PubMed

    Kainourgios, P; Efthimiadou, E K; Tziveleka, L-A; Pappas, G S; Boukos, N; Kordas, G

    2013-04-01

    In this report, the fabrication of hollow, pH-sensitive microspheres using the layer by layer method is being demonstrated. The process is based on the coating of colloidal silica templates with polyelectrolyte layers, followed by dissolution of the core using a buffer system of hydrofluoric acid and ammonium fluoride. With this buffer system, the template can be dissolved in mild pH conditions, where the polymeric layers are still stable. The resulting microspheres show pH dependent properties, where they swell and dissolve at a certain pH value. In order to improve the nanocontainers properties, such as solubility and cytotoxicity a second specimen of microspheres was fabricated by coating the fabricated microspheres with one layer of poly(acrylic acid) and one layer of methoxy-polyethylene glycol amine, and then these additional layers were crosslinked by carbodiimide chemistry. Loading and release properties of the fabricated microspheres have been studied in order to investigate their behavior as a function of pH and ionic strength. These novel microspheres have potential application in the fields of drug delivery, diagnostics and life sciences.

  7. Cell specific, variable density, polymer microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

    1977-01-01

    Biocompatible polymeric microspheres having an average diameter below about 3 microns and having density at least 15% greater or lesser than organic cells and having covalent binding sites are provided in accordance with this invention. The microspheres are obtained by copolymerizing a hydroxy or amine substituted acrylic monomer such as hydroxyethylmethacrylate with a light or dense comonomer such as a fluoromonomer. A lectin or antibody is bound to the hydroxy or amine site of the bead to provide cell specificity. When added to a cell suspension the marked bead will specifically label the cell membrane by binding to specific receptor sites thereon. The labelled membrane can then be separated by density gradient centrifugation.

  8. Quantum Magnetomechanics with Levitating Superconducting Microspheres

    NASA Astrophysics Data System (ADS)

    Romero-Isart, O.; Clemente, L.; Navau, C.; Sanchez, A.; Cirac, J. I.

    2012-10-01

    We show that by magnetically trapping a superconducting microsphere close to a quantum circuit, it is possible to perform ground-state cooling and prepare quantum superpositions of the center-of-mass motion of the microsphere. Due to the absence of clamping losses and time-dependent electromagnetic fields, the mechanical motion of micrometer-sized metallic spheres in the Meissner state is predicted to be very well isolated from the environment. Hence, we propose to combine the technology of magnetic microtraps and superconducting qubits to bring relatively large objects to the quantum regime.

  9. Unusual imaging properties of superresolution microspheres.

    PubMed

    Li, Pin-Yi; Tsao, Yang; Liu, Yun-Ju; Lou, Zong-Xing; Lee, Wei-Li; Chu, Shi-Wei; Chang, Chih-Wei

    2016-07-25

    We employ a self-assembly method to fabricate dielectric microsphere arrays that can be transferred to any desired positions. The arrays not only enable far-field, broad-band, high-speed, large-area, and wide-angle field of views but also achieve superresolution reaching λ/6.4. We also find that many proposed theories are insufficient to explain the imaging properties; including the achieved superresolution, effects of immersion, and unusual size-dependent magnification. The half-immersed microspheres certainly do not behave like any ordinary solid immersion lenses and new mechanisms must be incorporated to explain their unusual imaging properties. PMID:27464101

  10. Study on immobilization of lipase onto magnetic microspheres with epoxy groups

    NASA Astrophysics Data System (ADS)

    Lei, Lin; Bai, Yongxiao; Li, Yanfeng; Yi, Liuxiang; Yang, Yong; Xia, Chungu

    2009-02-01

    Magnetic microspheres were synthesized by the suspension polymerization of glycidyl methacrylate (GMA), methacrylic acid (MAA) and divinyl benzene (DVB) in the presence of oleic acid-coated Fe 3O 4 nanoparticles. Triacylglycerol lipase from porcine pancreas was covalently immobilized on the magnetic microspheres via the active epoxy groups with the activity yield up to 63% (±2.3%) and enzyme loading of 39 (±0.5) mg/g supports. The resulting immobilized lipase had higher optimum temperature compared with those of free lipase and exhibited better thermal, broader pH stability and excellent reusability. Furthermore, the catalyzed capability of immobilized lipase was also investigated by catalyzing synthesis of hexyl acetate and the esterification conversion rate reached to 83% (±2.5%) after 12 h in nonaqueous solvent.

  11. Development, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres as a depot system for parenteral delivery.

    PubMed

    Sinha, Vivek Ranjan; Trehan, Aman

    2008-08-01

    Ketorolac tromethamine, a potent nonnarcotic analgesic agent and 800 times more potent than aspirin, is indicated for the short-term management of moderate to such severe painful states as post operative pain, acute musculoskeletal pain, and dental pain. It Given every 6 hr intramuscularly in patients for acute pain, to avoid frequent dosing and patient inconvenience Ketorolac from ethamine was found suitable for parenteral depot system by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers viz. polycaprolactone, poly-dl-lactide (Resomer) and poly lactic acid (PLA). To tailor the release profile of drug for several days, blends of Resomer and PLA were prepared with polycaprolactone in different ratios. Higher encapsulation efficiency was obtained with microspheres made with pure Resomer. Surface topography was studied by scanning electron microscopy, which showed spherical shape of microspheres. Residual solvent analysis was carried out to determine the residual amount of dichloromethane in microspheres and the content was found within permissible limits. Differential scanning calorimetric studies also were carried out to study any drug polymer interactions. We concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.

  12. Design and evaluation of surface and adjuvant modified PLGA microspheres for uptake by dendritic cells to improve vaccine responses.

    PubMed

    Salvador, Aiala; Sandgren, Kerrie J; Liang, Frank; Thompson, Elizabeth A; Koup, Richard A; Pedraz, José Luis; Hernandez, Rosa Maria; Loré, Karin; Igartua, Manoli

    2015-12-30

    Designing strategies for targeting antigens to dendritic cells is a major goal in vaccinology. Here, PLGA (poly lactic-co-glycolic acid) microspheres and with several surface modifications that affect to their uptake by human blood primary dendritic cells and monocytes have been evaluated. Higher uptake was found by all the cell types when cationic microspheres (PLGA modified with polyethylene imine) were used. These cationic particles were in vivo evaluated in mice. In addition, MPLA(1) or poly(I:C)(2) and α-GalCer(3) were also encapsulated to address their adjuvant effect. All the microspheres were able to produce humoral immune responses, albeit they were higher for cationic microspheres. Moreover, surface charge seemed to have a role on biasing the immune response; cationic microspheres induced higher IFN-γ levels, indicative of Th1 activation, while unmodified ones mainly triggered IL4 and IL17A release, showing Th2 activation. Thus, we have shown here the potential and versatility of these MS, which may be tailored to needs.

  13. One-step fabrication of inorganic/organic hybrid microspheres with tunable surface texture for controlled drug release application.

    PubMed

    Dong, Hua; Tang, Guannan; Ma, Ting; Cao, Xiaodong

    2016-01-01

    In this paper, we report one-step fabrication of poly(lactide-co-glycolic acid)/titanium oxide (PLGA/TiO2) hybrid microspheres with tunable surface texture via droplet-based microfluidics. Surface texture of microspheres can be continuously tuned by changing the mass ratio between titanium tetraisopropoxide (TTIP) and PLGA in the dispersed phase. The fast hydrolysis of TTIP on the droplet surface can generate a thin shell membrane, resulting in a wrinkled surface after extraction of organic solvent. In vitro drug release monitoring of tanshinone IIA-loaded PLGA/TiO2 hybrid microsphere reveals that surface texture can affect the drug release rate to a large extent without sacrificing the drug encapsulation efficiency. Our finding might benefit the sustained drug delivery where variable drug release rate and high drug encapsulation efficiency are both required. PMID:26610930

  14. Optimization of the preparation of nalmefene-loaded sustained-release microspheres using central composite design.

    PubMed

    Wu, Xiang-Gen; Li, Gao; Gao, Yong-Liang

    2006-07-01

    Nalmefene-loaded poly(lactic-co-glycolic acid) microspheres were prepared by O/O emulsification/solvent evaporation method. The central composite design-response surface methodology was used to optimize and predict the preparation microspheres. Effects of three independent variable variables i.e., Span80 concentration in outer phase, poly(lactic-co-glycolic acid) concentration in inner phase and theoretical drug content were evaluated on a number of response variables. Response variables selected in this study were drug content, encapsulation efficiency, mean diameter, diameter span and the cumulative percentage of the drug released in the first day after incubation (marked as F1d, and it was also calculated as the initial burst). Multiple linear regression and second-order polynomial model were fitted to the data, and the resulting equations were used to produce five dimensional response graphs, by which optimal experimental conditions were selected. The results showed that all response variables were greatly dependent on three independent variables, and the optimal conditions were Span80 concentration 1.5%, poly(lactic-co-glycolic acid) concentration 17.5%, and theoretical drug content 6%. According to the optimal conditions, the drug content, encapsulation efficiency, mean diameter, diameter span and F1d of prepared microspheres were 4.37%, 72.8%, 64.1 microm, 1.36 and 8.93%, respectively.

  15. Microsphere-based scaffolds encapsulating tricalcium phosphate and hydroxyapatite for bone regeneration.

    PubMed

    Gupta, Vineet; Lyne, Dina V; Barragan, Marilyn; Berkland, Cory J; Detamore, Michael S

    2016-07-01

    Bioceramic mixtures of tricalcium phosphate (TCP) and hydroxyapatite (HAp) are widely used for bone regeneration because of their excellent cytocompatibility, osteoconduction, and osteoinduction. Therefore, we hypothesized that incorporation of a mixture of TCP and HAp in microsphere-based scaffolds would enhance osteogenesis of rat bone marrow stromal cells (rBMSCs) compared to a positive control of scaffolds with encapsulated bone-morphogenic protein-2 (BMP-2). Poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds encapsulating TCP and HAp mixtures in two different ratios (7:3 and 1:1) were fabricated with the same net ceramic content (30 wt%) to evaluate how incorporation of these ceramic mixtures would affect the osteogenesis in rBMSCs. Encapsulation of TCP/HAp mixtures impacted microsphere morphologies and the compressive moduli of the scaffolds. Additionally, TCP/HAp mixtures enhanced the end-point secretion of extracellular matrix components relevant to bone tissue compared to the "blank" (PLGA-only) microsphere-based scaffolds as evidenced by the biochemical, gene expression, histology, and immunohistochemical characterization. Moreover, the TCP/HAp mixture groups even surpassed the BMP-2 positive control group in some instances in terms of matrix synthesis and gene expression. Lastly, gene expression data suggested that the rBMSCs responded differently to different TCP/HAp ratios presented to them. Altogether, it can be concluded that TCP/HAp mixtures stimulated the differentiation of rBMSCs toward an osteoblastic phenotype, and therefore may be beneficial in gradient microsphere-based scaffolds for osteochondral regeneration. PMID:27272903

  16. Stability study of full-length antibody (anti-TNF alpha) loaded PLGA microspheres.

    PubMed

    Marquette, S; Peerboom, C; Yates, A; Denis, L; Langer, I; Amighi, K; Goole, J

    2014-08-15

    Antibodies (Abs) require the development of stable formulations and specific delivery strategies given their susceptibility to a variety of physical and chemical degradation pathways. In this study, the encapsulation of an antibody into polylactide-co-glycolide (PLGA) based microspheres was explored to obtain a controlled-release of the incorporated drug. In order to avoid stability issues, a solid-in-oil-in-water (s/o/w) method was preferred. The solid phase was made of anti-TNF alpha monoclonal antibody (MAb) spray-dried microparticles, and the PLGA microspheres were produced using two different polymers (i.e., Resomer(®) RG505 and Resomer(®) RG755S). The stability of the MAb incorporated into the microspheres was investigated under three conditions (5 ± 3°C, 25 ± 2°C/60% RH and 40 ± 2°C/75% RH) for 12 weeks. During this stability study, it was demonstrated that the MAb loaded PLGA microspheres were stable when stored at 5 ± 3°C and that the Resomer(®) RG755S, composed of 75%(w/w) lactic acid as PLGA, was preferred to preserve the stability of the system. Storage at temperatures higher than 5°C led to antibody stability issues such as aggregation, fragmentation and loss of activity. The release profiles were also altered. Physical ageing of the system associated with changes in the glass transition temperature and enthalpy of relaxation was noticed during the storage of the MAb loaded PLGA microspheres.

  17. Stability study of full-length antibody (anti-TNF alpha) loaded PLGA microspheres.

    PubMed

    Marquette, S; Peerboom, C; Yates, A; Denis, L; Langer, I; Amighi, K; Goole, J

    2014-08-15

    Antibodies (Abs) require the development of stable formulations and specific delivery strategies given their susceptibility to a variety of physical and chemical degradation pathways. In this study, the encapsulation of an antibody into polylactide-co-glycolide (PLGA) based microspheres was explored to obtain a controlled-release of the incorporated drug. In order to avoid stability issues, a solid-in-oil-in-water (s/o/w) method was preferred. The solid phase was made of anti-TNF alpha monoclonal antibody (MAb) spray-dried microparticles, and the PLGA microspheres were produced using two different polymers (i.e., Resomer(®) RG505 and Resomer(®) RG755S). The stability of the MAb incorporated into the microspheres was investigated under three conditions (5 ± 3°C, 25 ± 2°C/60% RH and 40 ± 2°C/75% RH) for 12 weeks. During this stability study, it was demonstrated that the MAb loaded PLGA microspheres were stable when stored at 5 ± 3°C and that the Resomer(®) RG755S, composed of 75%(w/w) lactic acid as PLGA, was preferred to preserve the stability of the system. Storage at temperatures higher than 5°C led to antibody stability issues such as aggregation, fragmentation and loss of activity. The release profiles were also altered. Physical ageing of the system associated with changes in the glass transition temperature and enthalpy of relaxation was noticed during the storage of the MAb loaded PLGA microspheres. PMID:24792974

  18. Active self-healing encapsulation of vaccine antigens in PLGA microspheres

    PubMed Central

    Desai, Kashappa-Goud H.; Schwendeman, Steven P.

    2013-01-01

    Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 μm, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer

  19. Method for introduction of gases into microspheres

    DOEpatents

    Hendricks, C.D.; Koo, J.C.; Rosencwaig, A.

    A method is described for producing small hollow glass spheres filled with a gas by introduction of the gas during formation of the hollow glass spheres. Hollow glass microspheres having a diameter up to about 500..mu.. with both thin walls (0.5 to 4/sub ..mu../) and thick walls (5 to 20/sub ..mu../) that contain various fill gases, such as Ar, Kr, Xe, Br, D, H/sub 2/, DT, He, N/sub 2/, Ne, CO/sub 2/, etc., in the interior thereof, can be produced by the diffusion of the fill gas or gases into the microsphere during the formation thereof from a liquid droplet of glass-form-forming solution. This is accomplished by filling at least a portion of the multiple-zone drop-furnace used in producing hollow microspheres with the gas or gases of interest, and then taking advantage of the high rate of gaseous diffusion of the fill gas through the wall of the gel membrane before it transforms into a glass microsphere as it is processed in the multiple-zone furnace.

  20. Preparation of small bio-compatible microspheres

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping S. (Inventor); Dreyer, William J. (Inventor)

    1979-01-01

    Small, round, bio-compatible microspheres capable of covalently bonding proteins and having a uniform diameter below about 3500 A are prepared by substantially instantaneously initiating polymerization of an aqueous emulsion containing no more than 35% total monomer including an acrylic monomer substituted with a covalently bondable group such a hydroxyl, amino or carboxyl and a minor amount of a cross-linking agent.

  1. Beat-Frequency/Microsphere Medical Ultrasonic Imaging

    NASA Technical Reports Server (NTRS)

    Yost, William T.; Cantrell, John H.; Pretlow, Robert A., III

    1995-01-01

    Medical ultrasonic imaging system designed to provide quantitative data on various flows of blood in chambers, blood vessels, muscles, and tissues of heart. Sensitive enough to yield readings on flows of blood in heart even when microspheres used as ultrasonic contrast agents injected far from heart and diluted by circulation of blood elsewhere in body.

  2. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... within or to an organ. (b) Classification. Class III (premarket approval). (c) Date PMA or notice of completion of a PDP is required. A PMA or notice of completion of a PDP is required to be filed with the Food... other trace microsphere shall have an approved PMA or a declared completed PDP in effect before...

  3. 21 CFR 870.1360 - Trace microsphere.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... within or to an organ. (b) Classification. Class III (premarket approval). (c) Date PMA or notice of completion of a PDP is required. A PMA or notice of completion of a PDP is required to be filed with the Food... other trace microsphere shall have an approved PMA or a declared completed PDP in effect before...

  4. Electrostatic Assembly of Sandwich-like Ag-C@ZnO-C@Ag-C Hybrid Hollow Microspheres with Excellent High-Rate Lithium Storage Properties.

    PubMed

    Xie, Qingshui; Ma, Yating; Wang, Xuanpeng; Zeng, Deqian; Wang, Laisen; Mai, Liqiang; Peng, Dong-Liang

    2016-01-26

    Herein, we introduce a facile electrostatic attraction approach to produce zinc-silver citrate hollow microspheres, followed by thermal heating treatment in argon to ingeniously synthesize sandwich-like Ag-C@ZnO-C@Ag-C hybrid hollow microspheres. The 3D carbon conductive framework in the hybrids derives from the in situ carbonation of carboxylate acid groups in zinc-silver citrate hollow microspheres during heating treatment, and the continuous and homogeneous Ag nanoparticles on the outer and inner surfaces of hybrid hollow microspheres endow the shells with the sandwiched configuration (Ag-C@ZnO-C@Ag-C). When applied as the anode materials for lithium ion batteries, the fabricated hybrid hollow microspheres with sandwich-like shells reveal a very large reversible capacity of 1670 mAh g(-1) after 200 cycles at a current density of 0.2 A g(-1). Even at the very large current densities of 1.6 and 10.0 A g(-1), the high specific capacities of about 1063 and 526 mAh g(-1) can be retained, respectively. The greatly enhanced electrochemical properties of Ag-C@ZnO-C@Ag-C hybrid microspheres are attributed to their special structural features such as the hollow structures, the sandwich-like shells, and the nanometer-sized building blocks.

  5. Formulation, characterization and evaluation of the effect of polymer concentration on the release behavior of insulin-loaded Eudragit®-entrapped mucoadhesive microspheres

    PubMed Central

    Kenechukwu, Franklin C.; Momoh, Mumuni A.

    2016-01-01

    Introduction: The aim of this study was to use Eudragit® RL 100 (pH-independent polymer) and magnesium stearate (a hydrophobic droplet stabilizer) in combination to improve the controlled release effect of insulin-loaded Eudragit® entrapped microspheres prepared by the emulsification-coacervation technique. Materials and Methods: Mucoadhesive insulin-loaded microspheres containing magnesium stearate and varying proportions of Eudragit® RL 100 were prepared by the emulsification-coacervation technique and evaluated for thermal properties, physicochemical performance, and in vitro dissolution in acidic and subsequently basic media. Results: Stable, spherical, brownish, discrete, free-flowing and mucoadhesive insulin-loaded microspheres with size range of 14.20 ± 0.30-19.80 ± 0.60 μm and loading efficiency of 74.55 ± 1.05-75.90 ± 1.94% were formed. After 3 h, microspheres prepared with insulin: Eudragit® RL 100 ratios of 1:4, 1:6, and 1:8 released 73.40 ± 1.38, 66.20 ± 1.59, and 71.30 ± 1.27 (%) of insulin, respectively. Conclusion: The physicochemical and physico-technical properties of the microspheres developed in this study demonstrated the effectiveness of the Eudragit® RL entrapped mucoadhesive microspheres (prepared by the emulsification-coacervation technique using varying polymer concentration) as a carrier system for oral insulin delivery. PMID:27051626

  6. Mechanism of the formation and growth of fine particles clustered polymer microspheres by simple one-step polymerization in aqueous alcohol system

    NASA Astrophysics Data System (ADS)

    Mao, Hui; Wen, Chao; Wu, Shuyao; Liu, Daliang; Zhang, Yu; Song, Xi-Ming

    2016-02-01

    By using the one-step copolymerization of styrene (St) and 1-vinyl-3-ethylimidazolium bromide (VEIB), fine particles clustered (FPC) poly(St-co-VEIB) microspheres have been successfully prepared in the present of sodium dodecylsulfonate (SDS) in aqueous alcohol system. The FPC poly(St-co-VEIB) microspheres are composed of small poly(St-co-VEIB) nanospheres with the average diameter of 40 nm. The formation mechanism of FPC poly(St-co-VEIB) microspheres is proposed by investigating the influence of reaction conditions on their morphologies and observing their growth process. It can be well convinced that VEIB not only acted as a kind of monomers, which participated in the polymerization and provided electropositivity for FPC poly(St-co-VEIB) microspheres, but also acted as emulsifier and reactive stabilizer. The FPC poly(St-co-VEI[SO3CF3]) microspheres, which were obtained by anion-exchange between -SO3CF3 of HSO3CF3 and Br- in FPC poly(St-co-VEIB) microspheres due to the existence of imidazolium groups with electropositivity, showed higher catalytic efficiency for hydration of 1,2-epoxypropane with H2O and esterification between acetic acid and ethanol than that of H2SO4.

  7. A new approach for the one-step synthesis of bioactive PS vs. PMMA silica hybrid microspheres as potential drug delivery systems.

    PubMed

    Angelopoulou, A; Efthimiadou, E K; Boukos, N; Kordas, G

    2014-05-01

    In this work, hybrid microspheres were prepared in a two-step process combining the emulsifier free-emulsion polymerization and the sol-gel coating method. In the first step, polystyrene (St) and poly(methyl methacrylate) (PMMA) microspheres were prepared as sacrificial template and in the second step a silanol shell was fabricated. The functionalized surface of the hybrid microspheres by silane analogs (APTES, TEOS) resulted in enhanced effects. The hollow microspheres were resulted either in an additional step by template dissolution and/or during the coating process. The microspheres' surface interactions and the size distribution were optimized by treatment in simulated body fluids, which resulted in the in vitro prediction of bioactivity. The bioassay test indicated that the induced hydroxyapatite resembled in structure to naturally occurring bone apatite. The drug doxorubicin (DOX) was used as a model entity for the evaluation of drug loading and release. The drug release study was performed in two different pH conditions, at acidic (pH=4.5) close to cancer cell environment and at slightly basic pH (pH=7.4) resembling the orthopedic environment. The results of the present study indicated promising hybrid microspheres for the potential application as drug delivery vehicles, for dual orthopedic functionalities in bone defects, bone inflammation, bone cancer and bone repair.

  8. Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase

    NASA Astrophysics Data System (ADS)

    Xue, Ping; Su, Weiguang; Gu, Yaohua; Liu, Haifeng; Wang, Julan

    2015-03-01

    Magnetic hydrophilic polymeric microspheres containing oxirane groups were prepared by inverse suspension polymerization of glycidyl methacrylate (GMA), N, N‧-methylene bisacrylamide (MBAA) and N-vinyl pyrrolidone (NVP) in the existence of formamide, which were denoted as magnetic poly(GMA-MBAA-NVP) microspheres. The magnetic poly(GMA-MBAA-NVP) microspheres were characterized by scanning electron microscopy (SEM), FT-IR spectroscopy, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and so on. The results showed that poly(GMA-MBAA-NVP) microspheres possessed well spherical shape, narrow size distribution, abundant porous structure, reactive oxirane groups and superparamagnetic properties. Formamide used in the present work served as a modifier, a dispersant and a porogen to form final porous polymer microspheres. The penicillin G acylase (PGA) was covalently immobilized onto the magnetic microspheres through the reaction between the amino groups of enzyme and the oxirane groups on the microspheres for producing 6-aminopenicillanic acid (6-APA). The effects of GMA/NVP ratio and crosslink density on the activity of immobilized PGA were investigated. The highest apparent activity, enzyme loading and coupling yield of immobilized PGA were 821 IU/g, 65.3 mg/g and 42.3% respectively when the mass ratio of GMA/NVP was 1:1 and crosslink density was 60%. Compared with the free PGA, immobilized PGA showed a wider range of pH value and reaction temperature. The relative activity and reaction rate of immobilized PGA remained almost constant after 20 recycles. The magnetic poly(GMA-MBAA-NVP) microspheres would be very promising carriers for immobilizing enzymes in industrial application.

  9. Preparation and evaluation of sustained release loxoprofen loaded microspheres

    PubMed Central

    Venkatesan, P.; Manavalan, R.; Valliappan, K.

    2011-01-01

    The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours PMID:24826017

  10. Method of detecting luminescent target ions with modified magnetic microspheres

    DOEpatents

    Shkrob, Ilya A; Kaminski, Michael D

    2014-05-13

    This invention provides methods of using modified magnetic microspheres to extract target ions from a sample in order to detect their presence in a microfluidic environment. In one or more embodiments, the microspheres are modified with molecules on the surface that allow the target ions in the sample to form complexes with specific ligand molecules on the microsphere surface. In one or more embodiments, the microspheres are modified with molecules that sequester the target ions from the sample, but specific ligand molecules in solution subsequently re-extract the target ions from the microspheres into the solution, where the complexes form independent of the microsphere surface. Once the complexes form, they are exposed to an excitation wavelength light source suitable for exciting the target ion to emit a luminescent signal pattern. Detection of the luminescent signal pattern allows for determination of the presence of the target ions in the sample.

  11. Optically Levitated Microspheres as a Probe for New Interactions

    NASA Astrophysics Data System (ADS)

    Rider, Alexander; Moore, David; Blakemore, Charles; Lu, Marie; Gratta, Giorgio

    2016-03-01

    We are developing novel techniques to probe new interactions at micron distances using optically levitated dielectric microspheres. Levitated microspheres are an ideal probe for short-range interactions because they are suspended using the radiation pressure at the focus of a laser beam, which means that the microspheres can be precisely manipulated and isolated from the surrounding environment at high vacuum. We have performed a search for unknown charged particles bound within the bulk of the microspheres. Currently, we are searching for the presence of a Chameleon field postulated to explain the presence of dark energy in the universe. In the future we plan to use optically levitated microspheres to search for micron length-scale gravity like interactions that could couple between a microsphere and another mass. We will present resent results from these experiments and plans for future searches for new interactions.

  12. Laser-assisted fabrication of highly viscous alginate microsphere

    NASA Astrophysics Data System (ADS)

    Lin, Yafu; Huang, Yong

    2011-04-01

    Encapsulated microspheres have been widely used in various biomedical applications. However, fabrication of encapsulated microspheres from highly viscous materials has always been a manufacturing challenge. The objective of this study is to explore a novel metallic foil-assisted laser-induced forward transfer (LIFT), a laser-assisted fabrication technique, to make encapsulated microspheres using high sodium alginate concentration solutions. The proposed four-layer approach includes a quartz disk, a sacrificial and adhesive layer, a metallic foil, and a transferred suspension layer. It is found that the proposed four-layer modified LIFT approach provides a promising fabrication technology for making of bead-encapsulated microspheres from highly viscous solutions. During the process, the microsphere only can be formed if the direct-writing height is larger than the critical direct-writing height; otherwise, tail structured droplets are formed; and the encapsulated microsphere diameter linearly increases with the laser fluence and decreases with the sodium alginate concentration.

  13. Investigation on the Synthesis and Photoluminescence of CaMoO4:Eu3+ Microspheres.

    PubMed

    Li, Jinping; Zhu, Gangqiang; Zhang, Tingting; Zheng, Hairong

    2016-04-01

    Eu3+ doped CaMoO4 microspheres were synthesized via a facile hydrothermal method assisted by the citric acid additive. The structure and morphology of the samples were examined by X-ray diffractometer (XRD) and scanning electron microscopy (SEM), and the properties of the photoluminescence emission from the samples were investigated with spectroscopic technique. The XRD results revealed that the hydrothermally formed CaMoO4:Eu3+ phosphor has single-phase scheelite-type tetragonal structure. The SEM observation demonstrated that the samples have sphere-like morphologies and their diameters were about 3-4 µm. Meanwhile, the influence of the citric acid on the formation of CaMoO4:Eu3+ was also investigated. The formation mechanism of CaMoO4:Eu3+ microspheres was explored based on the time-dependent experimental observation. The study on the luminescence spectra showed that CaMoO4:Eu3+ microspheres can be effectively excited at 395 nm, and good luminescence emission can be obtained at around 614 nm, which is attributed to the transition of 5D0 --> 7F2 from Eu3+. The current study suggests that CaMoO4:Eu3+ red phosphor is a potential candidate for white light-emitting diodes (WLEDs) application. PMID:27451741

  14. Beat frequency ultrasonic microsphere contrast agent detection system

    NASA Technical Reports Server (NTRS)

    Pretlow, III, Robert A. (Inventor); Yost, William T. (Inventor); Cantrell, Jr., John H. (Inventor)

    1997-01-01

    A system for and method of detecting and measuring concentrations of an ultrasonically-reflective microsphere contrast agent involving detecting non-linear sum and difference beat frequencies produced by the microspheres when two impinging signals with non-identical frequencies are combined by mixing. These beat frequencies can be used for a variety of applications such as detecting the presence of and measuring the flow rates of biological fluids and industrial liquids, including determining the concentration level of microspheres in the myocardium.

  15. (D, L) polylactide microspheres as embolic agent. A preliminary study.

    PubMed

    Flandroy, P; Grandfils, C; Collignon, J; Thibaut, A; Nihant, N; Barbette, S; Jerome, R; Teyssie, P

    1990-01-01

    Owing to their shape, accurately calibrated microspheres appear to be very suitable material for distal embolization. Moreover, the biocompatible (D, L) polyactide (PLA) microspheres possess two other valuable advantages: easy adjustment of their biodegradation rate, and incorporation of chemotherapeutic agents during their production. The authors describe the preparation of these (D, L) PLA microspheres and their clinical applications as a preliminary step to arterial chemoembolization. PMID:2234391

  16. Evaluation of parameters influencing the molecular delivery by biodegradable microsphere-mediated perforation using femtosecond laser

    NASA Astrophysics Data System (ADS)

    Mitsuhashi, Tatsuki; Terakawa, Mitsuhiro

    2014-01-01

    The parameters critically influencing the delivery rate on the biodegradable microsphere-mediated femtosecond (fs) laser perforation are investigated in detail with the aim of developing efficient molecular delivery. Cell membrane was perforated by the irradiation of weakly focused fs laser pulses to the spherical polylactic acid microspheres conjugated to the cell membrane. The delivery of fluorescein isothiocyanate-dextran and fluorescent silica particles to A431 cells is investigated in detail. The increase in the number of irradiated laser pulses had resulted in the increase of delivery rate. The delivery rate depends on the size and functionalization of fluorescent silica particles in which silica particles of 100 nm in diameter were able to be delivered into 20% of the irradiated cells, suggesting that the pore sizes are large enough for the delivery of therapeutic agents into cells. These findings contribute to the development of an efficient and safe phototherapy and drug delivery.

  17. SrCO3:Tb3+ hollow microspheres fabricated via solvothermal process and their optical properties

    NASA Astrophysics Data System (ADS)

    Xue, Yannan; Ren, Xiaolei; Yu, Min

    2012-08-01

    Well-dispersed SrCO3:Tb3+ hollow microspheres have been synthesized in the water-ethanol-ethylene glycol solvent system using oleic acid (OA) as an additive without further annealing treatment. X-ray diffraction (XRD), fourier transform-infrared spectroscopy (FT-IR), and field emission scanning electron microscopy (FE-SEM), as well as photoluminescence spectroscopy (PL) were used to characterize the resulting samples. The dosage of OA and the reaction time play key roles in the formation of the final samples. The possible formation mechanism for SrCO3:Tb3+ hollow microsphere is proposed. The SrCO3:Tb3+ phosphors show strong photoluminescence with green emission 5D4-7F5 (544 nm) as the most prominent group under ultraviolet excitation, which have potential applications in field emission displays. The present synthesis process may be extended to fabricate other inorganic materials with special morphologies and functions.

  18. Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines

    NASA Astrophysics Data System (ADS)

    Wang, Chun; Ge, Qing; Ting, David; Nguyen, David; Shen, Hui-Rong; Chen, Jianzhu; Eisen, Herman N.; Heller, Jorge; Langer, Robert; Putnam, David

    2004-03-01

    Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.

  19. Preparation of uniform magnetic recoverable catalyst microspheres with hierarchically mesoporous structure by using porous polymer microsphere template

    PubMed Central

    2014-01-01

    Merging nanoparticles with different functions into a single microsphere can exhibit profound impact on various applications. However, retaining the unique properties of each component after integration has proven to be a significant challenge. Our previous research demonstrated a facile method to incorporate magnetic nanoparticles into porous silica microspheres. Here, we report the fabrication of porous silica microspheres embedded with magnetic and gold nanoparticles as magnetic recoverable catalysts. The as-prepared multifunctional composite microspheres exhibit excellent magnetic and catalytic properties and a well-defined structure such as uniform size, high surface area, and large pore volume. As a result, the very little composite microspheres show high performance in catalytic reduction of 4-nitrophenol, special convenient magnetic separability, long life, and good reusability. The unique nanostructure makes the microspheres a novel stable and highly efficient catalyst system for various catalytic industry processes. PMID:24708885

  20. Preparation of porous zirconia microspheres by internal gelation method

    SciTech Connect

    Pathak, Sachin S.; Pius, I.C. Bhanushali, R.D.; Rao, T.V. Vittal; Mukerjee, S.K.

    2008-11-03

    A modified internal gelation process for the preparation of porous zirconia microspheres has been developed. The conventional method has been modified by adding a surfactant in the feed broth. The effects of variation of surfactant concentration, washing techniques and temperature of calcination on the pore volume and the surface area of the microspheres have been studied. The conditions were optimized to obtain porous stable microspheres suitable for various applications. The microspheres were characterized by surface area analysis, pore volume analysis, thermogravimetric analysis and X-ray diffraction. The ion exchange behavior was studied using pH titration.

  1. Fluorescent Microspheres as Point Sources: A Localization Study.

    PubMed

    Chao, Jerry; Lee, Taiyoon; Ward, E Sally; Ober, Raimund J

    2015-01-01

    The localization of fluorescent microspheres is often employed for drift correction and image registration in single molecule microscopy, and is commonly carried out by fitting a point spread function to the image of the given microsphere. The mismatch between the point spread function and the image of the microsphere, however, calls into question the suitability of this localization approach. To investigate this issue, we subject both simulated and experimental microsphere image data to a maximum likelihood estimator that localizes a microsphere by fitting an Airy pattern to its image, and assess the suitability of the approach by evaluating the ability of the estimator to recover the true location of the microsphere with the best possible accuracy as determined based on the Cramér-Rao lower bound. Assessing against criteria based on the standard errors of the mean and the variance for an ideal estimator of the microsphere's location, we find that microspheres up to 100 nm in diameter can in general be localized using a fixed width Airy pattern, and that microspheres as large as 1 μm in diameter can in general be localized using a floated width Airy pattern. PMID:26218251

  2. Chitosan microspheres as a delivery system for nasal insufflation.

    PubMed

    Patil, Sanjay B; Sawant, Krutika K

    2011-06-01

    The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres for nasal delivery. The microspheres were prepared by emulsification-crosslinking method and evaluated for morphology, particle size, swelling index, in vitro mucoadhesion and delivery properties from Miat(®) nasal insufflator. The results showed that the microspheres were spherical in shape with smooth surfaces. The particle size of microspheres was found to be dependent on the concentration of the chitosan. The mean particle size was significantly increased when high concentration of chitosan was used. Aqueous to oil phase ratio, stirring rate and dioctyl sodium sulfosuccinate (DOSS) concentration also influenced the particle size distribution of the microspheres. It was found that, as stirring rate was increased, the size of the microspheres was decreased. The volume of glutaraldehyde and crosslinking time had very slight effect on particle size distribution. The % equilibrium water uptake of the microspheres was ranged from 124% to 232% and the mucoadhesive strength from 70.64±2.14 to 86.32±3.96%. The results of powder delivery from the device showed that, almost entire amount was delivered after three puffs. The images of the delivery sequences of microsphere powder clouds demonstrated that microspheres were delivered forming an elongated puff. The core of the clouds was homogeneous which can be expected to provide effective distribution pattern.

  3. Patterning of silica microsphere monolayers with focused femtosecond laser pulses

    SciTech Connect

    Cai Wenjian; Piestun, Rafael

    2006-03-13

    We demonstrate the patterning of monolayer silica microsphere lattices with tightly focused femtosecond laser pulses. We selectively removed microspheres from a lattice and characterized the effect on the lattice and the substrate. The proposed physical mechanism for the patterning process is laser-induced breakdown followed by ablation of material. We show that a microsphere focuses radiation in its interior and in the near field. This effect plays an important role in the patterning process by enhancing resolution and accuracy and by reducing the pulse energy threshold for damage. Microsphere patterning could create controlled defects within self-assembled opal photonic crystals.

  4. The xanthene dyes doped PMMA microspheres for optical sensor applications

    NASA Astrophysics Data System (ADS)

    Miluski, Piotr; Dorosz, Dominik; Kochanowicz, Marcin; Zmojda, Jacek; Dorosz, Jan

    2015-12-01

    The numerous applications of luminescent glass and polymeric microspheres are well known. The polymeric structures are popular as they assure good processability (solid and porous structures) and high doping level. The article presents the suspension polymerization process of polymeric (PMMA) microspheres doped by xanthene dyes: Fluorescein (Fl) and Rhodamine B (RhB). The bright luminescence at wavelengths 510nm 595nm respectively was recorded. The shape and dimension distributions of fabricated microspheres were optically determined. The article presents also potential applications of fabricated luminescent microspheres.

  5. Fiber optic chemical microsensors employing optically active silica microspheres

    NASA Astrophysics Data System (ADS)

    Pope, Edward J. A.

    1995-05-01

    Dye-doped porous silica microspheres can be prepared from liquid solution at temperatures near ambient. Microsphere diameter can be controlled between approximately 5.0 microns to in excess of a millimeter. The resulting microspheres can be attached to the distal end of an optical fiber in which the proximal end is attached to a spectrophotometer. Depending upon the organic species doped into the microsphere, a wide variety of sensing functions are possible. In this paper, the use of microsensors for measuring pH, temperature, and solvent content of aqueous solutions is demonstrated. Potential utility of this type of sensor to heavy metals detection and biomedical diagnostics is also discussed.

  6. Imaging of drug loading distributions in individual microspheres of calcium silicate hydrate - an X-ray spectromicroscopy study

    NASA Astrophysics Data System (ADS)

    Guo, Xiaoxuan; Wang, Zhiqiang; Wu, Jin; Wang, Jian; Zhu, Ying-Jie; Sham, Tsun-Kong

    2015-04-01

    Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere.Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07471h

  7. Design of cationic microspheres based on aminated gelatin for controlled release of peptide and protein drugs.

    PubMed

    Morimoto, Kazuhiro; Chono, Sumio; Kosai, Tadashi; Seki, Toshinobu; Tabata, Yasuhiko

    2008-02-01

    Two different types of cationized microspheres based on a native cationic gelatin (NGMS) and aminated gelatin with ethylendiamine (CGMS) were investigated for the controlled release of three model acidic peptide/protein drugs with different molecular weights (MWs) and isoelectric points (IEPs). Recombinant human (rh)-insulin (MW: 5.8 kDa, IEP: 5.3), bovine milk lactoalbumin, BMLA (MW: 14 kDa, IEP: 4.3), and bovine serum albumin (BSA MW: 67 kDa, IEP: 4.9) were used as model acidic peptide/protein drugs. The in vitro release profiles of these acidic peptide/protein drugs from NGMS and CGMS were compared and different periods of cross-linking were obtained. The slower release of these acidic peptide/protein drugs from CGMS compared with those from NGMS with cross-linking for 48 hr. was caused by the suppression of burst release during the initial phase. The degree of suppression of burst release of the three peptide/protein drugs during the initial phase by CGMS was in the following order: (rh)-insulin > BMLA > BSA. The release of insulin with a lower molecular weight from CGMS was particularly suppressed compared with the other two drugs with higher molecular weights in the initial phase. The control of the release rate of acidic peptide/protein drugs from gelatin microsphere can be achieved by amination of gelatin. Therefore, CGMS is useful for the controlled release of acidic peptide/ protein drugs.

  8. Cell specific, variable density, polymer microspheres

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping S. (Inventor); Rembaum, Alan (Inventor); Molday, Robert S. (Inventor)

    1978-01-01

    Biocompatible polymeric microspheres having an average diameter below about 3 microns and having a density at least 15% greater or lesser than organic cells and having covalent binding sites are provided in accordance with this invention. The microspheres are obtained by copolymerizing a hydroxy or amine substituted acrylic monomer such as hydroxyethylmethacrylate with a light or dense comonomer such as a fluoromonomer. A lectin or antibody is bound to the hydroxy or amine site of the bead to provide cell specificity. When added to a cell suspension the marked bead will specifically label the cell membrane by binding to specific receptor sites thereon. The labelled membrane can then be separated by density gradient centrifugation.

  9. Fluorescence dynamics of microsphere-adsorbed sunscreens

    NASA Astrophysics Data System (ADS)

    Krishnan, R.

    2005-03-01

    Sunscreens are generally oily substances which are prepared in organic solvents, emulsions or dispersions with micro- or nanoparticles. These molecules adsorb to and integrate into skin cells. In order to understand the photophysical properties of the sunscreen, we compare steady-state and time-resolved fluorescence in organic solvent of varying dielectric constant ɛ and adsorbed to polystyrene microspheres and dispersed in water. Steady-state fluorescence is highest and average fluorescence lifetime longest in toluene, the solvent of lowest ɛ. However, there is no uniform dependence on ɛ. Sunscreens PABA and padimate-O show complex emission spectra. Microsphere-adsorbed sunscreens exhibit highly non-exponential decay, illustrative of multiple environments of the adsorbed molecule. The heterogeneous fluorescence dynamics likely characterizes sunscreen adsorbed to cells.

  10. Neutron transmission measurements on hydrogen filled microspheres

    NASA Astrophysics Data System (ADS)

    Dyrnjaja, Eva; Hummel, Stefan; Keding, Marcus; Smolle, Marie-Theres; Gerger, Joachim; Zawisky, Michael

    2014-01-01

    Hollow microspheres are promising candidates for future hydrogen storage technologies. Although the physical process for hydrogen diffusion through glass is well understood, measurements of static quantities (e.q. hydrogen pressure inside the spheres) as well as dynamic properties (e.g. diffusion rate of hydrogen through glass) are still difficult to handle due to the small size of the spheres (d≈15μm). For diffusion rate measurements, the long-term stability of the experiment is also mandatory due to the relatively slow diffusion rate. In this work, we present an accurate and long-term stable measurement technique for static and dynamic properties, using neutron radiography. Furthermore, possible applications for hydrogen filled microspheres within the scope of radiation issues are discussed.

  11. Ultrasound-modulated shape memory and payload release effects in a biodegradable cylindrical rod made of chitosan-functionalized PLGA microspheres.

    PubMed

    Bao, Min; Zhou, Qihui; Dong, Wen; Lou, Xiangxin; Zhang, Yanzhong

    2013-06-10

    Minimally invasive implants and/or scaffolds integrated with multiple functionalities are of interest in the clinical settings. In this paper, chitosan (CTS) functionalized poly(lactic-co-glycolic acid) (PLGA) microspheres containing a model payload, lysozyme (Lyz), were prepared by a water-in-oil-in-water emulsion method, from which cylindrical shaped rod (5 mm in diameter) was fabricated by sintering the composite microspheres in a mold. High-intensity focused ultrasound (HIFU) was then employed as a unique technique to enable shape memory and payload release effects of the three-dimensional (3-D) structure. It was found that incorporation of CTS into PLGA microspheres could regulate the transition temperature Ttrans of the microsphere from 45 to 50 °C and affect shape memory ratio of the fabricated cylindrical rod to some extent. Shape memory test and drug release assay proved that HIFU could modulate the shape recovery process and synchronize the release kinetics of the encapsulated Lyz in the rod in a switchable manner. Moreover, the two processes could be manipulated by varying the acoustic power and insonation duration. Mechanical tests of the microspheres-based rod before and after ultrasound irradiation revealed its compressive properties in the range of trabecular bone. Examination of the degradation behavior indicated that the introduction of CTS into the PLGA microspheres also alleviated acidic degradation characteristic of the PLGA-dominant cylindrical rod. With HIFU, this study thus demonstrated the desired capabilities of shape recovery and payload release effects integrated in one microspheres-based biodegradable cylindrical structure. PMID:23675980

  12. Sputter coating of microspherical substrates by levitation

    DOEpatents

    Lowe, A.T.; Hosford, C.D.

    Microspheres are substantially uniformly coated with metals or nonmetals by simltaneously levitating them and sputter coating them at total chamber pressures less than 1 torr. A collimated hole structure comprising a parallel array of upwardly projecting individual gas outlets is machined out to form a dimple. Glass microballoons,, which are particularly useful in laser fusion applications, can be substantially uniformly coated using the coating method and apparatus.

  13. Sputter coating of microspherical substrates by levitation

    DOEpatents

    Lowe, Arthur T.; Hosford, Charles D.

    1981-01-01

    Microspheres are substantially uniformly coated with metals or nonmetals by simultaneously levitating them and sputter coating them at total chamber pressures less than 1 torr. A collimated hole structure 12 comprising a parallel array of upwardly projecting individual gas outlets 16 is machined out to form a dimple 11. Glass microballoons, which are particularly useful in laser fusion applications, can be substantially uniformly coated using the coating method and apparatus.

  14. Optimization of sustained release aceclofenac microspheres using response surface methodology.

    PubMed

    Deshmukh, Rameshwar K; Naik, Jitendra B

    2015-03-01

    Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14±0.015% to 85.34±0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12h. The optimized microspheres formulation showed E.E. of 84.87±0.005 with small error value (1.39). The low magnitudes of error and the significant value of R(2) in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects.

  15. Pulmonary toxicity of Expancel microspheres in the rat.

    PubMed

    Porter, Dale W; Hubbs, Ann F; Baron, Paul A; Millecchia, Lyndell L; Wolfarth, Michael G; Battelli, Lori A; Schwegler-Berry, Diane E; Beighley, Christopher M; Andrew, Michael E; Castranova, Vincent

    2007-08-01

    Expancel microspheres are thermoplastic microspheres enclosing hydrocarbon. These microspheres expand when heated, producing many applications. Because they have unknown biological persistence and toxicity, we investigated the toxicity of two unexpanded (11.1 and 15.4 micro m mean diameter) and two expanded (3.1 and 5.5 micro m mass median aerodynamic diameter) Expancel microspheres in intratracheally-instilled, male, Sprague-Dawley rats. Pulmonary histopathology was evaluated at 28 days postexposure. Bronchoalveolar lavage fluid was evaluated at days 1, 7, 14, and 28 days postexposure. Crystalline silica was the positive control. By histopathology, both unexpanded and expanded microspheres caused granulomatous bronchopneumonia characterized by macrophages and giants cells, suggesting a persistent foreign body response. Expanded, but not unexpanded microspheres, also caused eosinophilic bronchitis and bronchiolitis, mucous metaplasia of airways and organized granulomatous inflammation with associated fibrosis and frequent airway obstruction. In contrast, alveolar macrophage activation, polymorphonuclear leukocytes, LDH and albumin in bronchoalveolar laveage fluid were initially elevated but returned to near control levels at 28 days, and did not reflect the persistent granulomatous bronchopneumonia caused by Expancel microspheres. These findings emphasize the importance of histopathology for evaluating pulmonary toxicity, suggest that Expancel microspheres are a potential occupational hazard, and indicate a need for additional studies on their potential pulmonary toxicity. [Supplementary materials are available for this article. Go to the publisher's online edition of Toxicology Pathology for the following free supplemental resources: motion within unexpected microspheres in H&E-stained lung (supplementary Figure 1); broncholar epithelium 28 days following exposure to 551 DE 20 microspheres (supplementary Figure 2); membrane ruffling and some instances of

  16. Mucoadhesive Microspheres Containing Amoxicillin for Clearance of Helicobacter pylori

    PubMed Central

    Nagahara, Naoki; Akiyama, Yohko; Nakao, Masafumi; Tada, Mayumi; Kitano, Megumi; Ogawa, Yasuyuki

    1998-01-01

    In an effort to augment the anti-Helicobacter pylori effect of amoxicillin, mucoadhesive microspheres, which have the ability to reside in the gastrointestinal tract for an extended period, were prepared. The microspheres contained the antimicrobial agent and an adhesive polymer (carboxyvinyl polymer) powder dispersed in waxy hydrogenated castor oil. The percentage of amoxicillin remaining in the stomach both 2 and 4 h after oral administration of the mucoadhesive microspheres to Mongolian gerbils under fed conditions was about three times higher than that after administration in the form of a 0.5% methylcellulose suspension. The in vivo clearance of H. pylori following oral administration of the mucoadhesive microspheres and the 0.5% methylcellulose suspension to infected Mongolian gerbils was examined under fed conditions. The mucoadhesive microspheres and the 0.5% methylcellulose suspension both showed anti-H. pylori effects in this experimental model of infection, but the required dose of amoxicillin was effectively reduced by a factor of 10 when the mucoadhesive microspheres were used. In conclusion, the mucoadhesive microspheres more effectively cleared H. pylori from the gastrointestinal tract than the 0.5% methylcellulose suspension due to the prolonged gastrointestinal residence time resulting from mucoadhesion. A dosage form consisting of mucoadhesive microspheres containing an appropriate antimicrobial agent should be useful for the eradication of H. pylori. PMID:9756746

  17. Porous-wall hollow glass microspheres as carriers for biomolecules

    DOEpatents

    Li, Shuyi; Dynan, William S; Wicks, George; Serkiz, Steven

    2013-09-17

    The present invention includes compositions of porous-wall hollow glass microspheres and one or more biomolecules, wherein the one or more biomolecules are positioned within a void location within the hollow glass microsphere, and the use of such compositions for the diagnostic and/or therapeutic delivery of biomolecules.

  18. Characterization of carbon cryogel microspheres as adsorbents for VOC.

    PubMed

    Yamamoto, Takuji; Kataoka, Sho; Ohmori, Takao

    2010-05-15

    Adsorption characteristics of carbon cryogel microspheres (CC microspheres) with controlled porous structure composed of mesopores (2 nmmicrospheres could be changed by varying either the size of the mesopores or the volume of the micropores. The peak temperature of the temperature-programmed desorption profiles of toluene from the CC microspheres was higher than that from granular activated carbon (GAC) with numerous micropores, indicating that toluene is adsorbed more strongly on CC microspheres than on GAC. To permit the practical use of CC microspheres, the adsorption characteristic of moisture on CC microspheres and GAC were evaluated. The effect of adsorption of moisture on the gas permeation property of an adsorption module prepared from the CC microspheres was also examined. PMID:20042276

  19. Fluorescent Microspheres as Point Sources: A Localization Study

    PubMed Central

    Chao, Jerry; Lee, Taiyoon; Ward, E. Sally; Ober, Raimund J.

    2015-01-01

    The localization of fluorescent microspheres is often employed for drift correction and image registration in single molecule microscopy, and is commonly carried out by fitting a point spread function to the image of the given microsphere. The mismatch between the point spread function and the image of the microsphere, however, calls into question the suitability of this localization approach. To investigate this issue, we subject both simulated and experimental microsphere image data to a maximum likelihood estimator that localizes a microsphere by fitting an Airy pattern to its image, and assess the suitability of the approach by evaluating the ability of the estimator to recover the true location of the microsphere with the best possible accuracy as determined based on the Cramér-Rao lower bound. Assessing against criteria based on the standard errors of the mean and the variance for an ideal estimator of the microsphere’s location, we find that microspheres up to 100 nm in diameter can in general be localized using a fixed width Airy pattern, and that microspheres as large as 1 μm in diameter can in general be localized using a floated width Airy pattern. PMID:26218251

  20. Pectin/zein microspheres as a sustained drug delivery system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A series of microspheres were prepared from pectins and corn proteins from various sources in the presence of the divalent ions calcium or zinc. The results showed that the yield of microsphere and the efficiency of drug incorporation were dependent on the type and ratio of biopolymers, the size of ...

  1. Rapid biomimetic mineralization of hydroxyapatite-g-PDLLA hybrid microspheres.

    PubMed

    Du, Ke; Shi, Xudong; Gan, Zhihua

    2013-12-10

    Hydroxyapatite-graft-poly(D,L-lactide) (HA-g-PDLLA) nanoparticles were synthesized here to fabricate hybrid microspheres with diameter in the range of 150-200 μm by emulsion solvent evaporation techniques. The as-obtained microspheres were treated with alkaline solution in order to selectively degrade the PDLLA layer which covered on the surface of hybrid microspheres and instead to generate a dense coating of HA nanoparticles. The hybrid microspheres with enriched HA nanoparticles on the surface were further immersed in simulated body fluid (SBF) solution to evaluate the bone-forming ability of the bioactive hybrid microspheres via the in vitro biomimetic mineralization process. The resultant microspheres were analyzed by using X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) to understand the nucleation and growth of bioactive calcium phosphate (Ca-P) crystals as a function of surface treatment. Results in this work clearly demonstrated that the existing HA nanoparticles on the surface of hybrid microspheres after alkaline treatment greatly affect the growth of the bone-like Ca-P crystals in SBF solutions. The biomimetic hybrid microspheres were found to be excellent candidates for use as injectable scaffolds for bone tissue engineering.

  2. High-capacity anion exchangers based on poly (glycidylmethacrylate-divinylbenzene) microspheres for ion chromatography.

    PubMed

    Liu, Junwei; Wang, Yong; Cheng, Heli; Wang, Nani; Wu, Shuchao; Zhang, Peimin; Zhu, Yan

    2016-10-01

    Poly (glycidylmethacrylate-divinylbenzene) microspheres were prepared by the two-staged swelling and polymerization method and applied to prepare anion exchange stationary phases. Methylamine, dimethylamine, trimethylamine, diethylamine and triethylamine were selected to prepare the quaternary ammonium groups of anion exchangers, respectively. The diameters and surface characteristics of microspheres were measured by scanning electron microscope and nitrogen adsorption-desorption measurements. The anion exchangers were characterized by Fourier transform infrared spectrum, elemental analysis and breakthrough curve methods. The chromatographic performances of anion exchangers were illustrated by separating conventional anions, organic weak acids and carbohydrates. The results indicated that the anion exchange capacities were controllable by changing either the content of glycidylmethacrylate in microspheres or the number of bonded quaternary ammonium layer. Meanwhile, the substituents of quaternary ammonium groups greatly influenced the separation properties of anion exchangers. Finally, the three-layer methylamine-quaternized anion exchanger was successfully applied for the determination of fluoride in tea sample. The content of fluoride was detected to be 0.13mgg(-1) without the interference of acetate and formate. PMID:27474308

  3. Microsphere-Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells.

    PubMed

    Patel, Madhumita; Moon, Hyo Jung; Jung, Bo Kyung; Jeong, Byeongmoon

    2015-07-15

    Neuronal differentiation of tonsil-derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)-poly(l-alanine) aqueous solution to 37 °C through the heat-induced sol-to-gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs. The neuronal growth factors are released over 12-18 d, and the TMSCs in a spherical shape initially undergo multipolar elongation during the 3D culture. Significantly higher expressions of the neuronal biomarkers such as nuclear receptor related protein (Nurr-1), neuron specific enolase, microtubule associated protein-2, neurofilament-M, and glial fibrillary acidic protein are observed in both mRNA level and protein level in the hybrid systems than in the control experiments. This study proves the significance of a controlled drug delivery concept in tissue engineering or regenerative medicine, and a 3D hybrid system with controlled release of growth factors from microspheres in a thermogel can be a very promising tool. PMID:26033880

  4. Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.

    PubMed

    Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

    2015-05-01

    Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules.

  5. Microsphere-Incorporated Hybrid Thermogel for Neuronal Differentiation of Tonsil Derived Mesenchymal Stem Cells.

    PubMed

    Patel, Madhumita; Moon, Hyo Jung; Jung, Bo Kyung; Jeong, Byeongmoon

    2015-07-15

    Neuronal differentiation of tonsil-derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)-poly(l-alanine) aqueous solution to 37 °C through the heat-induced sol-to-gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs. The neuronal growth factors are released over 12-18 d, and the TMSCs in a spherical shape initially undergo multipolar elongation during the 3D culture. Significantly higher expressions of the neuronal biomarkers such as nuclear receptor related protein (Nurr-1), neuron specific enolase, microtubule associated protein-2, neurofilament-M, and glial fibrillary acidic protein are observed in both mRNA level and protein level in the hybrid systems than in the control experiments. This study proves the significance of a controlled drug delivery concept in tissue engineering or regenerative medicine, and a 3D hybrid system with controlled release of growth factors from microspheres in a thermogel can be a very promising tool.

  6. Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules

    PubMed Central

    Carpenedo, Richard L.; Bratt-Leal, Andrés M.; Marklein, Ross A.; Seaman, Scott A.; Bowen, Nathan J.; McDonald, John F.; McDevitt, Todd C.

    2010-01-01

    Cell specification and tissue formation during embryonic development are precisely controlled by the local concentration and temporal presentation of morphogenic factors. Similarly, pluripotent embryonic stem cells can be induced to differentiate in vitro into specific phenotypes in response to morphogen treatment. Embryonic stem cells (ESCs) are commonly differentiated as 3D spheroids referred to as embryoid bodies (EBs); however, differentiation of cells within EBs is typically heterogeneous and disordered. In this study, we demonstrate that in contrast to soluble morphogen treatment, delivery of morphogenic factors directly within EB microenvironments in a spatiotemporally controlled manner using polymer microspheres yields homogeneous, synchronous and organized ESC differentiation. Degradable PLGA microspheres releasing retinoic acid were incorporated directly within EBs and induced the formation of cystic spheroids uniquely resembling the phenotype and structure of early streak mouse embryos (E6.75), with an exterior of FOXA2+ visceral endoderm enveloping an epiblast-like layer of OCT4+ cells. These results demonstrate that controlled morphogen presentation to stem cells using degradable microspheres more efficiently directs cell differentiation and tissue formation than simple soluble delivery methods and presents a unique route to study the spatiotemporal effects of morphogenic factors on embryonic developmental processes in vitro. PMID:19162317

  7. Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings

    PubMed Central

    Shen, Jie; Burgess, Diane J.

    2011-01-01

    Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under “real-time” and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to “real-time” conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict “real-time” release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under “real-time” and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. PMID:22016033

  8. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair.

    PubMed

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei; Tao, Xiaojun; Zhang, Zhihua; Sun, Xiaomin; Zhang, Qiqing

    2016-04-01

    For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration.

  9. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair.

    PubMed

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei; Tao, Xiaojun; Zhang, Zhihua; Sun, Xiaomin; Zhang, Qiqing

    2016-04-01

    For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration. PMID:26838900

  10. Influence of clay particles on microfluidic-based preparation of hydrogel composite microsphere

    NASA Astrophysics Data System (ADS)

    Hong, Joung Sook

    2016-05-01

    For the successful fabrication of a hydrogel composite microsphere, this study aimed to investigate the influence of clay particles on microsphere formation in a microfluidic device which has flow focusing and a 4.5:1 contraction channel. A poly alginic acid solution (2.0 wt.%) with clay particles was used as the dispersed phase to generate drops in an oil medium, which then merged with drops of a CaCl2 solution for gelation. Drop generations were observed with different flow rates and particles types. When the flow rate increased, drop generation was enhanced and drop size decreased by the build-up of more favorable hydrodynamic flow conditions to detach the droplets. The addition of a small amount of particles insignificantly changed the drop generation behavior even though it reduced interfacial tension and increased the viscosity of the solution. Instead, clays particles significantly affected hydro-gelation depending on the hydrophobicity of particles, which produced further heterogeneity in the shape and size of microsphere.

  11. Molecularly imprinted ionic liquid magnetic microspheres for the rapid isolation of organochlorine pesticides in environmental water.

    PubMed

    Qiao, Fengxia; Gao, Mengmeng; Yan, Hongyuan

    2016-04-01

    A new type of molecularly imprinted ionic liquid magnetic microspheres was synthesized by aqueous suspension polymerization, using 4,4'-dichlorobenzhydrol as a dummy template, and 1-allyl-3-ethylimidazolium hexafluorophosphate and methacrylic acid as co-functional monomers. The results of morphology and magnetic property evaluation of the obtained microspheres demonstrated that it was monodispersed spherical, possessed a rough surface, and an outstanding magnetic properties. Binding experiments revealed that it had a substantial adsorption capacity and strong recognition ability to organochlorine pesticides (OCPs) in aqueous solution. Then the microspheres were applied as an adsorbent of magnetic dispersive solid-phase extraction for the selective recognition and rapid determination of OCPs in environmental water. Under the optimum conditions, good linearity of the three types of OCPs (dicofol, tetradifon, and p,p'-dichlorodiphenyldichloroethane) was achieved in the range of 1.0-100 ng/mL (r ≥ 0.9994). The recoveries at three spiking levels ranged from 82.6 to 100.4% with the RSDs less than 6.9%.

  12. One for two: conversion of waste chicken feathers to carbon microspheres and (NH4)HCO3.

    PubMed

    Gao, Lei; Hu, Haibo; Sui, Xuelin; Chen, Changle; Chen, Qianwang

    2014-06-01

    Pyrolysis of 1 g of waste chicken feathers (quills and barbs) in supercritical carbon dioxide (sc-CO2) system at 600 °C for 3 h leads to the formation of 0.25 g well-shaped carbon microspheres with diameters of 1-5 μm and 0.26 g ammonium bicarbonate ((NH4)HCO3). The products were characterized by powder X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Raman spectroscopic, FT-IR spectrum, X-ray electron spectroscopy (XPS), and N2 adsorption/desorption measurements. The obtained carbon microspheres displayed great superhydrophobicity as fabric coatings materials, with the water contact angle of up to 165.2±2.5°. The strategy is simple, efficient, does not require any toxic chemicals or catalysts, and generates two valuable materials at the same time. Moreover, other nitrogen-containing materials (such as nylon and amino acids) can also be converted to carbon microspheres and (NH4)HCO3 in the sc-CO2 system. This provides a simple strategy to extract the nitrogen content from natural and man-made waste materials and generate (NH4)HCO3 as fertilizer.

  13. The Complex Sol-Gel Process for producing small ThO2 microspheres

    NASA Astrophysics Data System (ADS)

    Brykala, Marcin; Rogowski, Marcin

    2016-05-01

    Thorium based fuels offer several benefits compared to uranium based fuels thus they might be an attractive alternative to conventional fuel types. This study is devoted to the synthesis and the characterization of small thorium dioxide microspheres (Ø <50 μm). Their application involves using powder-free process, called the Complex Sol-Gel Process. The source sols used for the processes were prepared by the method where in the starting ascorbic acid solution the solid thorium nitrate was dissolved and partially neutralized by aqueous ammonia under pH control. The microspheres of thorium-ascorbate gel were obtained using the ICHTJ Process (INCT in English). Studies allowed to determine an optimal heat treatment with calcination temperature of 700 °C and temperature rate not higher than 2 °C/min which enabled us to obtain a crack-free surface of microspheres. The main parameters which have a strong influence on the synthesis method and features of the spherical particles of thorium dioxide are described in this article.

  14. Resolution enhancement phase-contrast imaging by microsphere digital holography

    NASA Astrophysics Data System (ADS)

    Wang, Yunxin; Guo, Sha; Wang, Dayong; Lin, Qiaowen; Rong, Lu; Zhao, Jie

    2016-05-01

    Microsphere has shown the superiority of super-resolution imaging in the traditional 2D intensity microscope. Here a microsphere digital holography approach is presented to realize the resolution enhancement phase-contrast imaging. The system is designed by combining the microsphere with the image-plane digital holography. A microsphere very close to the object can increase the resolution by transforming the object wave from the higher frequency to the lower one. The resolution enhancement amplitude and phase images can be retrieved from a single hologram. The experiments are carried on the 1D and 2D gratings, and the results demonstrate that the observed resolution has been improved, meanwhile, the phase-contrast image is obtained. The proposed method can improve the transverse resolution in all directions based on a single exposure. Furthermore, this system has extended the application of the microsphere from the conventional 2D microscopic imaging to 3D phase-contrast microscopic imaging.

  15. Hollow porous-wall glass microspheres for hydrogen storage

    DOEpatents

    Heung, Leung K.; Schumacher, Ray F.; Wicks, George G.

    2010-02-23

    A porous wall hollow glass microsphere is provided having a diameter range of between 1 to 200 microns, a density of between 1.0 to 2.0 gm/cc, a porous-wall structure having wall openings defining an average pore size of between 10 to 1000 angstroms, and which contains therein a hydrogen storage material. The porous-wall structure facilitates the introduction of a hydrogen storage material into the interior of the porous wall hollow glass microsphere. In this manner, the resulting hollow glass microsphere can provide a membrane for the selective transport of hydrogen through the porous walls of the microsphere, the small pore size preventing gaseous or liquid contaminants from entering the interior of the hollow glass microsphere.

  16. Optical cavity modes of a single crystalline zinc oxide microsphere.

    PubMed

    Moirangthem, Rakesh Singh; Cheng, Pi-Ju; Chien, Paul Ching-Hang; Ngo, Buu Trong Huynh; Chang, Shu-Wei; Tien, Chung-Hao; Chang, Yia-Chung

    2013-02-11

    A detailed study on the optical cavity modes of zinc oxide microspheres under the optical excitation is presented. The zinc oxide microspheres with diameters ranging from 1.5 to 3.0 µm are prepared using hydrothermal growth technique. The photoluminescence measurement of a single microsphere shows prominent resonances of whispering gallery modes at room temperature. The experimentally observed whispering gallery modes in the photoluminescence spectrum are compared with theoretical calculations using analytical and finite element methods in order to clarify resonance properties of these modes. The comparison between theoretical analysis and experiment suggests that the dielectric constant of the ZnO microsphere is somewhat different from that for bulk ZnO. The sharp resonances of whispering gallery modes in zinc oxide microspheres cover the entire visible window. They may be utilized in realizations of optical resonators, light emitting devices, and lasers for future chip integrations with micro/nano optoelectronic circuits, and developments of optical biosensors. PMID:23481759

  17. Novel sustained release microspheres for pulmonary drug delivery.

    PubMed

    Cook, Robert O; Pannu, Rupi K; Kellaway, Ian W

    2005-05-01

    A novel process for generating sustained release (SR) particles for pulmonary drug delivery is described. High purity nanoparticles of a hydrophilic, ionised drug are entrapped within hydrophobic microspheres using a spray-drying approach. Sustained release of the model drug, terbutaline sulphate (TS), from the microspheres was found to be proportional to drug loading and phospholipid content. Microspheres with a 33% drug loading exhibited sustained release of 32.7% over 180 min in phosphate buffer. Release was not significantly different in simulated lung fluids. No significant burst release was observed which suggested that nanoparticles were coated effectively during spray-drying. The absence of nanoparticles at the microsphere surface was confirmed with confocal microscopy. The sustained release microspheres were formulated as a carrier-free dry powder for inhalation, and exhibited a favourable Fine Particle Fraction (FPF) of 46.5+/-1.8% and Mass Median Aerodynamic Diameter (MMAD) of 3.93+/-0.12 microm. PMID:15866336

  18. Synthesis and characterization of magnetic poly(glycidyl methacrylate) microspheres

    NASA Astrophysics Data System (ADS)

    Horák, Daniel; Petrovský, Eduard; Kapička, Aleš; Frederichs, Theodor

    2007-04-01

    Magnetic nanoparticles encapsulated in poly(glycidyl methacrylate) microspheres were prepared and their detailed structural and magnetic characteristics given. Iron oxide nanoparticles were obtained by chemical coprecipitation of Fe(II) and Fe(III) salts and stabilized with dextran, (carboxymethyl)dextran or tetramethylammonium hydroxide. The microspheres were prepared by emulsion or dispersion polymerization of glycidyl methacrylate in the presence of ferrofluid. The microspheres were uniform both in shape and usually also in size; their size distribution was narrow. All the magnetic parameters confirm superparamagnetic nature of the microspheres. Blocking temperature was not observed, suggesting the absence of magnetic interactions at low temperatures. This is most probably caused by complete encapsulation and the absence of agglomeration. Such microspheres can be used in biomedical applications.

  19. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate

    PubMed Central

    Gupta, Vineet; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

    2015-01-01

    Extracellular matrix (ECM) components, such as chondroitin sulfate (CS) and tricalcium phosphate, serve as raw materials, and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical, and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds would enhance differentiation of rat bone marrow–derived stromal cells. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized ECM by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG), collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface. PMID:26191526

  20. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate.

    PubMed

    Gupta, Vineet; Mohan, Neethu; Berkland, Cory J; Detamore, Michael S

    2015-01-01

    Extracellular matrix (ECM) components, such as chondroitin sulfate (CS) and tricalcium phosphate, serve as raw materials, and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical, and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(d,l-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds would enhance differentiation of rat bone marrow-derived stromal cells. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized ECM by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG), collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface. PMID:26191526

  1. Development of an electrochemical biosensor methods based on acrylic microsphere for the determination of Arowana DNA hybridization

    NASA Astrophysics Data System (ADS)

    Rahman, Mahbubur; Heng, Lee Yook; Futra, Dedi; Chiang, Chew Poh

    2015-09-01

    An electrochemical method of Arowana DNA determination based of N-acrylosuccinimide (NAS) modified acrylic microsphere was fabricated. Hydrophobic succinimide functional group containing poly(n-butylacrylate-N-acryloxysuccinimide) microspheres were synthesized with a simple one-step photopolymerization pocedure. Aminated DNA probe was covalently bonded to the succinimde functional group of the acrylic microspheres. The hybridization of the immobilized DNA probe with the complementary DNA was determined by the differential pulse voltametry using anthraquninone-2-sulfonic acid monohydrate sodium salt (AQMS) as the electroactive hybridization label. The influences of many factors such as duration of DNA probe immobilization and hybridization, operational temperature and non-complementary DNA on the biosensor performance were evaluated. Under optimized conditions, the DNA microbiosensor demonstrated a wide linear response range to target DNA is 1.0 × 10-16 and 1.0 × 10-8 M with a lower limit of detection (LOD) of 9.46 × 10-17 M (R2 = 0.99) were calculated. This biosensor had improved the overall analytical performance of the resultant DNA microbiosensor when compared with other reported DNA biosensors using other nano-materials for membranes and microspheres as DNA immobilization matrices.

  2. Synthesis of peroxo-titanium decorated H-titanate-nanotube-based hierarchical microspheres with enhanced visible-light photocatalytic activity in degradation of Rhodamine B.

    PubMed

    Qiu, Yong; Li, Xinjun

    2014-10-21

    Peroxo-titanium decorated H-titanate-nanotube-based hierarchical microspheres (PTHM) with a large surface area (368 m(2) g(-1)) and mesoporous structure were prepared by an alkaline hydrothermal method in the presence of H2O2 followed by acid wash, and they exhibited improved activity in degradation of Rhodamine B under visible light irradiation.

  3. Ultrafast microsphere near-field nanostructuring

    NASA Astrophysics Data System (ADS)

    Leitz, K.-H.; Quentin, U.; Hornung, B.; Otto, A.; Alexeev, I.; Schmidt, M.

    2011-03-01

    Due to the steadily advancing miniaturization in all fields of technology nanostructuring becomes increasingly important. Whereas the classical lithographic nanostructuring suffers from both high costs and low flexibility, for many applications in biomedicine and technology laser based nanostructuring approaches, where near-field effects allow a sub-diffraction limited laser focusing, are on the rise. In combination with ultrashort pulsed laser sources, that allow the utilization of non-linear multi-photon absorption effects, a flexible, low-cost laser based nanostructuring with sub-wavelength resolution becomes possible. Among various near-field nanostructuring approaches the microsphere based techniques, which use small microbead particles of the size of the wavelength for a sub-diffraction limited focusing of pulsed laser radiation, are the most promising. Compared to the tip or aperture based techniques this approach is very robust and can be applied both for a large-scale production of periodic arrays of nanostructures and in combination with optical trapping also for a direct-write. Size and shape of the features produced by microsphere near-field nanostructuring strongly depend on the respective processing parameters. In this contribution a basic study of the influence of processing parameters on the microsphere near-field nanostructuring with nano-, pico- and femtosecond laser pulses will be presented. The experimental and numerical results with dielectric and metal nanoparticles on semiconductor and dielectric substrates show the influence of particle size and material, substrate material, pulse duration, laser fluence, number of contributing laser pulses and polarization on the structuring process.

  4. Core-shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate: synthesis using adenosine 5'-triphosphate and application in pH-responsive drug delivery.

    PubMed

    Lu, Bing-Qiang; Zhu, Ying-Jie; Chen, Feng; Qi, Chao; Zhao, Xin-Yu; Zhao, Jing

    2014-10-01

    Drug nanocarriers with magnetic targeting and pH-responsive drug-release behavior are promising for applications in controlled drug delivery. Magnetic iron oxides show excellent magnetism, but their application in drug delivery is limited by low drug-loading capacity and poor control over drug release. Herein, core-shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate (MIO@ACP) were prepared and investigated as magnetic, pH-responsive drug nanocarriers. Hollow microspheres of magnetic iron oxide (HMIOs) were prepared by etching solid MIO microspheres in hydrochloric acid/ethanol solution. After loading a drug into the HMIOs, the drug-loaded HMIOs were coated with a protective layer of ACP by using adenosine 5'-triphosphate (ATP) disodium salt (Na2 ATP) as stabilizer, and drug-loaded core-shell hollow microspheres of MIO@ACP (HMIOs/drug/ACP) were obtained. The as-prepared HMIOs/drug/ACP drug-delivery system exhibits superparamagnetism and pH-responsive drug-release behavior. In a medium with pH 7.4, drug release was slow, but it was significantly accelerated at pH 4.5 due to dissolution of the ACP shell. Docetaxel-loaded core-shell hollow microspheres of MIO@ACP exhibited high anticancer activity.

  5. Measurements of extrinsic fluorescence in Intralipid and polystyrene microspheres

    PubMed Central

    Du Le, Vinh Nguyen; Nie, Zhaojun; Hayward, Joseph E.; Farrell, Thomas J.; Fang, Qiyin

    2014-01-01

    The fluorescence of Intralipid and polystyrene microspheres with sphere diameter of 1 µm at a representative lipid and microsphere concentration for simulation of mucosal tissue scattering has not been a subject of extensive experimental study. In order to elucidate the quantitative relationship between lipid and microsphere concentration and the respective fluorescent intensity, the extrinsic fluorescence spectra between 360 nm and 650 nm (step size of 5 nm) were measured at different lipid concentrations (from 0.25% to 5%) and different microsphere concentrations (0.00364, 0.0073, 0.0131 spheres per cubic micrometer) using laser excitation at 355 nm with pulse energy of 2.8 µJ. Current findings indicated that Intralipid has a broadband emission between 360 and 650 nm with a primary peak at 500 nm and a secondary peak at 450 nm while polystyrene microspheres have a single peak at 500 nm. In addition, for similar scattering properties the fluorescence of Intralipid solutions is approximately three-fold stronger than that of the microsphere solutions. Furthermore, Intralipid phantoms with lipid concentrations ~2% (simulating the bottom layer of mucosa) produce up to seven times stronger fluorescent emission than phantoms with lipid concentration ~0.25% (simulating the top layer of mucosa). The fluoresence decays of Intralipid and microsphere solutions were also recorded for estimation of fluorescence lifetime. PMID:25136497

  6. Measurement of thermal diffusivity of depleted uranium metal microspheres

    NASA Astrophysics Data System (ADS)

    Humrickhouse-Helmreich, Carissa J.; Corbin, Rob; McDeavitt, Sean M.

    2014-03-01

    The high void space of nuclear fuels composed of homogeneous uranium metal microspheres may allow them to achieve ultra-high burnup by accommodating fuel swelling and reducing fuel/cladding interactions; however, the relatively low thermal conductivity of microsphere nuclear fuels may limit their application. To support the development of microsphere nuclear fuels, an apparatus was designed in a glovebox and used to measure the apparent thermal diffusivity of a packed bed of depleted uranium (DU) microspheres with argon fill in the void spaces. The developed Crucible Heater Test Assembly (CHTA) recorded radial temperature changes due to an initial heat pulse from a central thin-diameter cartridge heater. Using thermocouple positions and time-temperature data, the apparent thermal diffusivity was calculated. The thermal conductivity of the DU microspheres was calculated based on the thermal diffusivity from the CHTA, known material densities and specific heat capacities, and an assumed 70% packing density based on prior measurements. Results indicate that DU metal microspheres have very low thermal conductivity, relative to solid uranium metal, and rapidly form an oxidation layer even in a low oxygen environment. At 500 °C, the thermal conductivity of the DU metal microsphere bed was 0.431 ± 0.0560 W/m-K compared to the literature value of approximately 32 W/m-K for solid uranium metal.

  7. Insulin delivery through nasal route using thiolated microspheres.

    PubMed

    Nema, Tarang; Jain, Ashish; Jain, Aviral; Shilpi, Satish; Gulbake, Arvind; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93 µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62 ± 2.4% and 78.85 ± 3.1% in 6 h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23 ± 2.12% and 75.25 ± 0.93% blood glucose of initial BGL were observed at 6 h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.

  8. Magnetic poly(glycidyl methacrylate) microspheres for protein capture.

    PubMed

    Koubková, Jana; Müller, Petr; Hlídková, Helena; Plichta, Zdeněk; Proks, Vladimír; Vojtěšek, Bořivoj; Horák, Daniel

    2014-09-25

    The efficient isolation and concentration of protein antigens from complex biological samples is a critical step in several analytical methods, such as mass spectrometry, flow cytometry and immunochemistry. These techniques take advantage of magnetic microspheres as immunosorbents. The focus of this study was on the development of new superparamagnetic polymer microspheres for the specific isolation of the tumor suppressor protein p53. Monodisperse macroporous poly(glycidyl methacrylate) (PGMA) microspheres measuring approximately 5 μm and containing carboxyl groups were prepared by multistep swelling polymerization of glycidyl methacrylate (GMA), 2-[(methoxycarbonyl)methoxy]ethyl methacrylate (MCMEMA) and ethylene dimethylacrylate (EDMA) as a crosslinker in the presence of cyclohexyl acetate as a porogen. To render the microspheres magnetic, iron oxide was precipitated within their pores; the Fe content in the particles received ∼18 wt%. Nonspecific interactions between the magnetic particles and biological media were minimized by coating the microspheres with poly(ethylene glycol) (PEG) terminated by carboxyl groups. The carboxyl groups of the magnetic PGMA microspheres were conjugated with primary amino groups of mouse monoclonal DO-1 antibody using conventional carbodiimide chemistry. The efficiency of protein p53 capture and the degree of nonspecific adsorption on neat and PEG-coated magnetic microspheres were determined by western blot analysis.

  9. Ultra-sensitive force measurement using optically levitated microspheres

    NASA Astrophysics Data System (ADS)

    Rider, Alexander; Moore, David; Gratta, Giorgio

    2015-04-01

    We have demonstrated a novel technique for measuring microscopic forces acting on optically levitated dielectric microspheres. The radiation field at the focus of a laser beam is used to levitate a microsphere in a harmonic trap where its displacement can be determined by the pattern of scattered light. Optical levitation isolates the microsphere from the surrounding environment at high vacuum, making thermal noise negligible. We have demonstrated a preliminary sensitivity of 5 ×10-17NHz - 1 / 2 for forces acting on 5 μm microspheres and expect to be able to improve this by several orders of magnitude once non-fundamental sources of noise are eliminated. The electric charge of a microsphere can be determined by applying an electric field and measuring the resulting force. We have demonstrated the ability to discharge the microspheres with single electron precision, which eliminates the most significant electrostatic backgrounds from force measurements. As a demonstration of this technique we have searched for the presence of unknown charged particles with charge > 5 ×10-5 e bound in our microspheres. Here we discuss the apparatus, the charged particle search, and outline our plans for future measurements including gravity at μm length scales.

  10. The affinity of magnetic microspheres for Schistosoma eggs.

    PubMed

    Candido, Renata R F; Favero, Vivian; Duke, Mary; Karl, Stephan; Gutiérrez, Lucía; Woodward, Robert C; Graeff-Teixeira, Carlos; Jones, Malcolm K; St Pierre, Timothy G

    2015-01-01

    Schistosomiasis is a chronic parasitic disease of humans, with two species primarily causing the intestinal infection: Schistosoma mansoni and Schistosoma japonicum. Traditionally, diagnosis of schistosomiasis is achieved through direct visualisation of eggs in faeces using techniques that lack the sensitivity required to detect all infections, especially in areas of low endemicity. A recently developed method termed Helmintex™ is a very sensitive technique for detection of Schistosoma eggs and exhibits 100% sensitivity at 1.3 eggs per gram of faeces, enough to detect even low-level infections. The Helminthex™ method is based on the interaction of magnetic microspheres and schistosome eggs. Further understanding the underlying egg-microsphere interactions would enable a targeted optimisation of egg-particle binding and may thus enable a significant improvement of the Helmintex™ method and diagnostic sensitivity in areas with low infection rates. We investigated the magnetic properties of S. mansoni and S. japonicum eggs and their interactions with microspheres with different magnetic properties and surface functionalization. Eggs of both species exhibited higher binding affinity to the magnetic microspheres than the non-magnetic microspheres. Binding efficiency was further enhanced if the particles were coated with streptavidin. Schistosoma japonicum eggs bound more microspheres compared with S. mansoni. However, distinct differences within eggs of each species were also observed when the distribution of the number of microspheres bound per egg was modelled with double Poisson distributions. Using this approach, both S. japonicum and S. mansoni eggs fell into two groups, one having greater affinity for magnetic microspheres than the other, indicating that not all eggs of a species exhibit the same binding affinity. Our observations suggest that interaction between the microspheres and eggs is more likely to be related to surface charge-based electrostatic

  11. The affinity of magnetic microspheres for Schistosoma eggs.

    PubMed

    Candido, Renata R F; Favero, Vivian; Duke, Mary; Karl, Stephan; Gutiérrez, Lucía; Woodward, Robert C; Graeff-Teixeira, Carlos; Jones, Malcolm K; St Pierre, Timothy G

    2015-01-01

    Schistosomiasis is a chronic parasitic disease of humans, with two species primarily causing the intestinal infection: Schistosoma mansoni and Schistosoma japonicum. Traditionally, diagnosis of schistosomiasis is achieved through direct visualisation of eggs in faeces using techniques that lack the sensitivity required to detect all infections, especially in areas of low endemicity. A recently developed method termed Helmintex™ is a very sensitive technique for detection of Schistosoma eggs and exhibits 100% sensitivity at 1.3 eggs per gram of faeces, enough to detect even low-level infections. The Helminthex™ method is based on the interaction of magnetic microspheres and schistosome eggs. Further understanding the underlying egg-microsphere interactions would enable a targeted optimisation of egg-particle binding and may thus enable a significant improvement of the Helmintex™ method and diagnostic sensitivity in areas with low infection rates. We investigated the magnetic properties of S. mansoni and S. japonicum eggs and their interactions with microspheres with different magnetic properties and surface functionalization. Eggs of both species exhibited higher binding affinity to the magnetic microspheres than the non-magnetic microspheres. Binding efficiency was further enhanced if the particles were coated with streptavidin. Schistosoma japonicum eggs bound more microspheres compared with S. mansoni. However, distinct differences within eggs of each species were also observed when the distribution of the number of microspheres bound per egg was modelled with double Poisson distributions. Using this approach, both S. japonicum and S. mansoni eggs fell into two groups, one having greater affinity for magnetic microspheres than the other, indicating that not all eggs of a species exhibit the same binding affinity. Our observations suggest that interaction between the microspheres and eggs is more likely to be related to surface charge-based electrostatic

  12. The in vivo performance of CaP/PLGA composites with varied PLGA microsphere sizes and inorganic compositions.

    PubMed

    Hoekstra, Jan Willem M; Ma, Jinling; Plachokova, Adelina S; Bronkhorst, Ewald M; Bohner, Marc; Pan, Juli; Meijer, Gert J; Jansen, John A; van den Beucken, Jeroen J J P

    2013-07-01

    Enrichment of calcium phosphate (CaP) bone substitutes with poly(lactic-co-glycolic acid) (PLGA) microspheres to create porosity overcomes the problem of poor CaP degradation. The degradation of CaP-PLGA composites can be customized by changing the physical and chemical properties of PLGA and/or CaP. However, the effect of the size of dense (solid rather than hollow) PLGA microspheres in CaP has not previously been described. The present study aimed at determining the effect of different dense (i.e. solid) PLGA microsphere sizes (small (S) ~20μm vs. large (L) ~130μm) and of CaP composition (CaP with either anhydrous dicalcium phosphate (DCP) or calcium sulphate dihydrate (CSD)) on CaP scaffold biodegradability and subsequent bone in-growth. To this end mandibular defects in minipigs were filled with pre-set CaP-PLGA implants, with autologous bone being used as a control. After 4weeks the autologous bone group outperformed all CaP-PLGA groups in terms of the amount of bone present at the defect site. On the other hand, at 12weeks substantial bone formation was observed for all CaP-PLGA groups (ranging from 47±25% to 62±15%), showing equal amounts of bone compared with the autologous bone group (82±9%), except for CaP with DCP and large PLGA microspheres (47±25%). It was concluded that in the current study design the difference in PLGA microsphere size and CaP composition led to similar results with respect to scaffold degradation and subsequent bone in-growth. Further, after 12weeks all CaP-PLGA composites proved to be effective for bone substitution.

  13. Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth.

    PubMed

    Zhuang, Hai; Bu, Shoushan; Hua, Lei; Darabi, Mohammad A; Cao, Xiaojian; Xing, Malcolm

    2016-01-01

    In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide(®)). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable

  14. Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

    PubMed Central

    Zhuang, Hai; Bu, Shoushan; Hua, Lei; Darabi, Mohammad A; Cao, Xiaojian; Xing, Malcolm

    2016-01-01

    In this study, we fabricated glial cell-line derived neurotrophic factor (GDNF)-loaded microspheres, then seeded the microspheres in gelatin-methacrylamide hydrogel, which was finally integrated with the commercial bilayer collagen membrane (Bio-Gide®). The novel composite of nerve conduit was employed to bridge a 10 mm long sciatic nerve defect in a rat. GDNF-loaded gelatin microspheres had a smooth surface with an average diameter of 3.9±1.8 μm. Scanning electron microscopy showed that microspheres were uniformly distributed in both the GelMA gel and the layered structure. Using enzyme-linked immunosorbent assay, in vitro release studies (pH 7.4) of GDNF from microspheres exhibited an initial burst release during the first 3 days (18.0%±1.3%), and then, a prolonged-release profile extended to 32 days. However, in an acidic condition (pH 2.5), the initial release percentage of GDNF was up to 91.2%±0.9% within 4 hours and the cumulative release percentage of GDNF was 99.2%±0.2% at 48 hours. Then the composite conduct was implanted in a 10 mm critical defect gap of sciatic nerve in a rat. We found that the nerve was regenerated in both conduit and autograft (AG) groups. A combination of electrophysiological assessment and histomorphometry analysis of regenerated nerves showed that axonal regeneration and functional recovery in collagen tube filled with GDNF-loaded microspheres (GM + CT) group were similar to AG group (P>0.05). Most myelinated nerves were matured and arranged densely with a uniform structure of myelin in a neat pattern along the long axis in the AG and GM + CT groups, however, regenerated nerve was absent in the BLANK group, left the 10 mm gap empty after resection, and the nerve fiber exhibited a disordered arrangement in the collagen tube group. These results indicated that the hybrid system of bilayer collagen conduit and GDNF-loaded gelatin microspheres combined with gelatin-methacrylamide hydrogels could serve as a new biodegradable

  15. Development of packaged silica microspheres coupled with tapered optical microfibres

    NASA Astrophysics Data System (ADS)

    Wang, Pengfei; Madugani, Ramgopal; Zhao, Haoyu; Ward, Jonathan; Yang, Yong; Farrell, Gerald; Brambilla, Gilberto; Nic Chormaic, Síle

    2016-03-01

    In this research, we present a packaged add-drop filter composed of a silica microsphere resonator and a strongly coupled optical microfiber coupler. A one-step fabrication process using UV curable epoxy is shown to stabilize the microsphere resonator coupled to the microfiber coupler, which is used as add and drop ports. A high Q-factor of 3×107 is obtained at around 780 nm from the packaged microspheres coupled with the microfiber coupler in the add-drop configuration.

  16. Observation of whispering gallery modes in microtube-microspheres system

    NASA Astrophysics Data System (ADS)

    Li, Hanyang; Hao, Sue; Qiang, Liangsheng; Li, Jin; Zhang, Yundong

    2013-06-01

    We proposed that a fluorescent microsphere with diameter of 6 μm was manipulated into a microtube with inner diameter of 6.2 μm. The whispering gallery modes (WGMs) of fluorescence resonance were observed by 532 nm laser pumping the microspheres-mircotube system. Another microsphere with the same diameter was manipulated into the microtube and mode splitting in the system of two spheres in contact in the mircotube was demonstrated. We also discussed relationship between WGMs peak intensity and the excitation power. The scheme will bring more insight into the applications of WGMs for biomedical diagnostics and microfluidics.

  17. Development of prilling process for biodegradable microspheres through experimental designs.

    PubMed

    Fabien, Violet; Minh-Quan, Le; Michelle, Sergent; Guillaume, Bastiat; Van-Thanh, Tran; Marie-Claire, Venier-Julienne

    2016-02-10

    The prilling process proposes a microparticle formulation easily transferable to the pharmaceutical production, leading to monodispersed and highly controllable microspheres. PLGA microspheres were used for carrying an encapsulated protein and adhered stem cells on its surface, proposing a tool for regeneration therapy against injured tissue. This work focused on the development of the production of PLGA microspheres by the prilling process without toxic solvent. The required production quality needed a complete optimization of the process. Seventeen parameters were studied through experimental designs and led to an acceptable production. The key parameters and mechanisms of formation were highlighted. PMID:26656302

  18. Packaged chalcogenide microsphere resonator with high Q-factor

    NASA Astrophysics Data System (ADS)

    Wang, Pengfei; Ding, Ming; Lee, Timothy; Senthil Murugan, Ganapathy; Bo, Lin; Semenova, Yuliya; Wu, Qiang; Hewak, Dan; Brambilla, Gilberto; Farrell, Gerald

    2013-04-01

    The fabrication and characterization of a packaged As2S3 microsphere resonator coupled to a tapered fiber using a low refractive index UV-curable polymer are reported. Embedding provides an efficient means to remove the highest order whispering gallery modes in the microsphere resonator, thus cleaning the resonator spectrum. At wavelengths near 1549.5 nm, high-Q modes up to 1.8 × 105 can be efficiently excited in a 110 μm diameter chalcogenide microsphere via evanescent coupling from a 2 μm diameter tapered silica fiber. The device photosensitivity, useful for tuning, is still present and useable after the packaging process.

  19. Effect of size of silica microspheres on photonic band gap

    SciTech Connect

    Dhiman, N. Sharma, A. Gathania, A. K.; Singh, B. P.

    2014-04-24

    In present work photonic crystals of different size of silica microspheres have been fabricated. The optical properties of these developed photonic crystals have been studied using UV-visible spectroscopy. UV-visible spectroscopy shows that they have photonic band gap that can be tuned in visible and infrared regime by changing the size of silica microspheres. The photonic band gap structures of these photonic crystals have been calculated using MIT photonic band gap package. It also reveals that with the increase in size of silica microspheres the photonic band gap shifts to lower energy region.

  20. Protein specific fluorescent microspheres for labelling a protein

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1982-01-01

    Highly fluorescent, stable and biocompatible microspheres are obtained by copolymerizing an acrylic monomer containing a covalent bonding group such as hydroxyl, amine or carboxyl, for example, hydroxyethylmethacrylate, with an addition polymerizable fluorescent comonomer such as dansyl allyl amine. A lectin or antibody is bound to the covalent site to provide cell specificity. When the microspheres are added to a cell suspension the marked microspheres will specifically label a cell membrane by binding to a specific receptor site thereon. The labeled membrane can then be detected by fluorescence of the fluorescent monomer.

  1. Gas-generating TPGS-PLGA microspheres loaded with nanoparticles (NIMPS) for co-delivery of minicircle DNA and anti-tumoral drugs.

    PubMed

    Gaspar, Vítor M; Moreira, André F; Costa, Elisabete C; Queiroz, João A; Sousa, Fani; Pichon, Chantal; Correia, Ilídio J

    2015-10-01

    Drug-DNA combination therapies are receiving an ever growing focus due to their potential for improving cancer treatment. However, such approaches are still limited by the lack of multipurpose delivery systems that encapsulate drugs and condense DNA simultaneously. In this study, we describe the successful formulation of gas-generating pH-responsive D-α-tocopherol PEG succinate-poly(D,L-lactic-co-glycolic acid) (TPGS-PLGA) hollow microspheres loaded with both Doxorubicin (Dox) and minicircle DNA (mcDNA) nanoparticles as a strategy to co-deliver these therapeutics. For this study mcDNA vectors were chosen due to their increased therapeutic efficiency in comparison to standard plasmid DNA. The results demonstrate that TPGS-PLGA microcarriers can encapsulate Dox and chitosan nanoparticles completely condense mcDNA. The loading of mcDNA-nanoparticles into microspheres was confirmed by 3D confocal microscopy and co-localization analysis. The resulting TPGS-PLGA-Dox-mcDNA nanoparticle-in-microsphere hybrid carriers exhibit a well-defined spherical shape and neutral surface charge. Microcarriers incubation in acidic pH produced a gas-mediated Dox release, corroborating the microcarriers stimuli-responsive character. Also, the dual-loaded TPGS-PLGA particles achieved 5.2-fold higher cellular internalization in comparison with non-pegylated microspheres. This increased intracellular concentration resulted in a higher cytotoxic effect. Successful transgene expression was obtained after nanoparticle-mcDNA co-delivery in the microspheres. Overall these findings support the concept of using nanoparticle-microsphere multipart systems to achieve efficient co-delivery of various drug-mcDNA combinations.

  2. Preparation and properties of polyvinyl alcohol microspheres

    SciTech Connect

    Campbell, J.H.; Grens, J.Z.; Poco, J.F.; Ives, B.H.

    1986-06-01

    Polyvinyl alcohol (PVA) microspheres, having a size range of approx.150- to 250-..mu..m diameter with 1- to 5-..mu..m wall thickness, have been fabricated using a solution droplet technique. The spheres were developed for possible use on the Lawrence Livermore National Laboratory (LLNL) Inertial Confinement Fusion (ICF) Program. PVA, a polymer chosen based on earlier survey work carried out at KMS Fusion, Inc., has good strength, low hydrogen permeability, is optically transparent, and water soluble. The latter property makes it safe and easy to use in our droplet generator system. A unique dual-orifice droplet generator was used to prepare the spheres. The droplet generator operating conditions and the column processing parameters were chosen using results from our 1-D model calculations as a guide. The polymer microsphere model is an extension of the model we developed to support the glass sphere production. After preparation, the spheres were physically characterized for surface quality, sphericity, wall thickness (and uniformity), and size. We also determined the buckling pressure for both uncoated and CH-coated spheres. Radiation stability to beta decay (from tritium) was evaluated by exposing the spheres to a 7-keV electron beam. The results from these and other physical property measurements are presented in this report.

  3. Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

    PubMed

    Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

    2015-12-30

    Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms.

  4. Polycrystalline metasurface perfect absorbers fabricated using microsphere photolithography.

    PubMed

    Qu, Chuang; Kinzel, Edward C

    2016-08-01

    Microsphere photolithography (MPL) is a practical, cost-effective nanofabrication technique. It uses self-assembled microspheres in contact with the photoresist as microlenses. The microspheres focus incident light to a sub-diffraction limited array of photonic jets in the photoresist. This Letter explores the MPL technique to pattern metal-insulator-metal metasurfaces with near-perfect absorption at mid-wave infrared (MWIR) frequencies. Experimental results are compared to electromagnetic simulations of both the exposure process and the metasurface response. The microsphere self-assembly technique results in a polycrystalline metasurface; however, the metal-insulator-metal structure is shown to be defect tolerant. While the MPL approach imposes geometric constraints on the metasurface design, once understood, the technique can be used to create functional devices. In particular, the ability to tune the resonant wavelength with the exposure dose raises the potential of hierarchical structures.

  5. Super-focusing of center-covered engineered microsphere.

    PubMed

    Wu, Mengxue; Chen, Rui; Soh, Jiahao; Shen, Yue; Jiao, Lishi; Wu, Jianfeng; Chen, Xudong; Ji, Rong; Hong, Minghui

    2016-01-01

    Engineered microsphere possesses the advantage of strong light manipulation at sub-wavelength scale and emerges as a promising candidate to shrink the focal spot size. Here we demonstrated a center-covered engineered microsphere which can adjust the transverse component of the incident beam and achieve a sharp photonic nanojet. Modification of the beam width and working distance of the photonic nanojet were achieved by tuning the cover ratio of the engineered microsphere, leading to a sharp spot size which exceeded the optical diffraction limit. At a wavelength of 633 nm, a focal spot of 245 nm (0.387 λ) was achieved experimentally under plane wave illumination. Strong localized field with Bessel-like distribution was demonstrated by employing the linearly polarized beam and a center-covered mask being engineered on the microsphere. PMID:27528093

  6. Super-focusing of center-covered engineered microsphere.

    PubMed

    Wu, Mengxue; Chen, Rui; Soh, Jiahao; Shen, Yue; Jiao, Lishi; Wu, Jianfeng; Chen, Xudong; Ji, Rong; Hong, Minghui

    2016-01-01

    Engineered microsphere possesses the advantage of strong light manipulation at sub-wavelength scale and emerges as a promising candidate to shrink the focal spot size. Here we demonstrated a center-covered engineered microsphere which can adjust the transverse component of the incident beam and achieve a sharp photonic nanojet. Modification of the beam width and working distance of the photonic nanojet were achieved by tuning the cover ratio of the engineered microsphere, leading to a sharp spot size which exceeded the optical diffraction limit. At a wavelength of 633 nm, a focal spot of 245 nm (0.387 λ) was achieved experimentally under plane wave illumination. Strong localized field with Bessel-like distribution was demonstrated by employing the linearly polarized beam and a center-covered mask being engineered on the microsphere.

  7. Super-focusing of center-covered engineered microsphere

    NASA Astrophysics Data System (ADS)

    Wu, Mengxue; Chen, Rui; Soh, Jiahao; Shen, Yue; Jiao, Lishi; Wu, Jianfeng; Chen, Xudong; Ji, Rong; Hong, Minghui

    2016-08-01

    Engineered microsphere possesses the advantage of strong light manipulation at sub-wavelength scale and emerges as a promising candidate to shrink the focal spot size. Here we demonstrated a center-covered engineered microsphere which can adjust the transverse component of the incident beam and achieve a sharp photonic nanojet. Modification of the beam width and working distance of the photonic nanojet were achieved by tuning the cover ratio of the engineered microsphere, leading to a sharp spot size which exceeded the optical diffraction limit. At a wavelength of 633 nm, a focal spot of 245 nm (0.387 λ) was achieved experimentally under plane wave illumination. Strong localized field with Bessel-like distribution was demonstrated by employing the linearly polarized beam and a center-covered mask being engineered on the microsphere.

  8. Super-focusing of center-covered engineered microsphere

    PubMed Central

    Wu, Mengxue; Chen, Rui; Soh, Jiahao; Shen, Yue; Jiao, Lishi; Wu, Jianfeng; Chen, Xudong; Ji, Rong; Hong, Minghui

    2016-01-01

    Engineered microsphere possesses the advantage of strong light manipulation at sub-wavelength scale and emerges as a promising candidate to shrink the focal spot size. Here we demonstrated a center-covered engineered microsphere which can adjust the transverse component of the incident beam and achieve a sharp photonic nanojet. Modification of the beam width and working distance of the photonic nanojet were achieved by tuning the cover ratio of the engineered microsphere, leading to a sharp spot size which exceeded the optical diffraction limit. At a wavelength of 633 nm, a focal spot of 245 nm (0.387 λ) was achieved experimentally under plane wave illumination. Strong localized field with Bessel-like distribution was demonstrated by employing the linearly polarized beam and a center-covered mask being engineered on the microsphere. PMID:27528093

  9. Polycrystalline metasurface perfect absorbers fabricated using microsphere photolithography.

    PubMed

    Qu, Chuang; Kinzel, Edward C

    2016-08-01

    Microsphere photolithography (MPL) is a practical, cost-effective nanofabrication technique. It uses self-assembled microspheres in contact with the photoresist as microlenses. The microspheres focus incident light to a sub-diffraction limited array of photonic jets in the photoresist. This Letter explores the MPL technique to pattern metal-insulator-metal metasurfaces with near-perfect absorption at mid-wave infrared (MWIR) frequencies. Experimental results are compared to electromagnetic simulations of both the exposure process and the metasurface response. The microsphere self-assembly technique results in a polycrystalline metasurface; however, the metal-insulator-metal structure is shown to be defect tolerant. While the MPL approach imposes geometric constraints on the metasurface design, once understood, the technique can be used to create functional devices. In particular, the ability to tune the resonant wavelength with the exposure dose raises the potential of hierarchical structures. PMID:27472578

  10. Preparation of microspheres by an emulsification-complexation method.

    PubMed

    Kim, Jin-Chul; Song, Myeong-Eun; Lee, Eun-Joo; Park, Seung-Kyu; Rang, Moon-Jeong; Ahn, Ho-Jeong

    2002-04-01

    Microspheres were prepared by complexation of a cationic polymer, polyquaternium-24, and an anionic surfactant, sodium lauryl sulfate (SLS). The cationic polymer solution was emulsified in dimethylsiloxane to give water in silicone emulsion (W/Si), and it was used as a template for the formation of microspheres. The emulsion was dispersed into the SLS solution. In this process, two kinds of droplets, silicone dropletes and microspheres composed of the cationic polymer and SLS, were formed, evidenced by X-ray energy dispersive spectra. The mean diameter of the microspheres was reduced from 105.7 to 64.8 mum as the stirring rate for W/Si preparation increased from 300 to 1000 rpm. It is believed that water droplets in W/Si emulsion, when exposed to SLS solution, could be solidified by the complexation of the cationic polymer and the anionic surfactant.

  11. Super-Resolution Real Imaging in Microsphere-Assisted Microscopy

    PubMed Central

    Wang, Feifei; Li, Yi; Jia, Boliang; Liu, Lianqing; Li, Wen Jung

    2016-01-01

    Microsphere-assisted microscopy has received a lot of attention recently due to its simplicity and its capability to surpass the diffraction limit. However, to date, sub-diffraction-limit features have only been observed in virtual images formed through the microspheres. We show that it is possible to form real, super-resolution images using high-refractive index microspheres. Also, we report on how changes to a microsphere’s refractive index and size affect image formation and planes. The relationship between the focus position and the additional magnification factor is also investigated using experimental and theoretical methods. We demonstrate that such a real imaging mode, combined with the use of larger microspheres, can enlarge sub-diffraction-limit features up to 10 times that of wide-field microscopy’s magnification with a field-of-view diameter of up to 9 μm. PMID:27768774

  12. Preparation of microspheres by an emulsification-complexation method.

    PubMed

    Kim, Jin-Chul; Song, Myeong-Eun; Lee, Eun-Joo; Park, Seung-Kyu; Rang, Moon-Jeong; Ahn, Ho-Jeong

    2002-04-01

    Microspheres were prepared by complexation of a cationic polymer, polyquaternium-24, and an anionic surfactant, sodium lauryl sulfate (SLS). The cationic polymer solution was emulsified in dimethylsiloxane to give water in silicone emulsion (W/Si), and it was used as a template for the formation of microspheres. The emulsion was dispersed into the SLS solution. In this process, two kinds of droplets, silicone dropletes and microspheres composed of the cationic polymer and SLS, were formed, evidenced by X-ray energy dispersive spectra. The mean diameter of the microspheres was reduced from 105.7 to 64.8 mum as the stirring rate for W/Si preparation increased from 300 to 1000 rpm. It is believed that water droplets in W/Si emulsion, when exposed to SLS solution, could be solidified by the complexation of the cationic polymer and the anionic surfactant. PMID:16290495

  13. BIOCOMPATIBLE FLUORESCENT MICROSPHERES: SAFE PARTICLES FOR MATERIAL PENETRATION STUDIES

    SciTech Connect

    Farquar, G; Leif, R

    2009-07-15

    Biocompatible polymers with hydrolyzable chemical bonds have been used to produce safe, non-toxic fluorescent microspheres for material penetration studies. The selection of polymeric materials depends on both biocompatibility and processability, with tailored fluorescent properties depending on specific applications. Microspheres are composed of USFDA-approved biodegradable polymers and non-toxic fluorophores and are therefore suitable for tests where human exposure is possible. Micropheres were produced which contain unique fluorophores to enable discrimination from background aerosol particles. Characteristics that affect dispersion and adhesion can be modified depending on use. Several different microsphere preparation methods are possible, including the use of a vibrating orifice aerosol generator (VOAG), a Sono-Tek atomizer, an emulsion technique, and inkjet printhead. Applications for the fluorescent microspheres include challenges for biodefense system testing, calibrants for biofluorescence sensors, and particles for air dispersion model validation studies.

  14. X- And y-axis driver for rotating microspheres

    DOEpatents

    Weinstein, Berthold W.

    1979-01-01

    Apparatus for precise control of the motion and position of microspheres for examination of their interior and/or exterior. The apparatus includes an x- and y-axis driver mechanism controlled, for example, by a minicomputer for selectively rotating microspheres retained between a pair of manipulator arms having flat, smooth end surfaces. The driver mechanism includes an apertured plate and ball arrangement which provided for coupled equal and opposite movement of the manipulator arms in two perpendicular directions.

  15. Hierarchical {001}-faceted BiOBr microspheres as a novel biomimetic catalyst: dark catalysis towards colorimetric biosensing and pollutant degradation

    NASA Astrophysics Data System (ADS)

    Li, Lili; Ai, Lunhong; Zhang, Caihong; Jiang, Jing

    2014-04-01

    In recent years, considerable effort has been devoted to finding novel enzyme mimetics with improved catalytic activities. However, the insightful understanding of such catalytic process is still elusive. In this paper, we report for the first time a typical photoactive layer-structured BiOBr as a novel biomimetic catalyst possessing highly efficient intrinsic peroxidase-like activity. Moreover, we have experimentally achieved high dark peroxidase-like catalytic activity in BiOBr microspheres and provided some new insights into the light-enhanced peroxidase-like catalytic property. On the basis of a typical color reaction derived from catalytic oxidation of peroxidase substrates over BiOBr microspheres with H2O2, the simple and sensitive colorimetric assays for detection of H2O2, glucose and ascorbic acid were successfully established. More interestingly, the BiOBr microspheres showed strong ability towards activation of H2O2, displaying excellent dark catalytic activity for the degradation of organic dye. It is therefore believed that our findings in this study could open up the possibility of utilizing BiOBr as enzymatic mimics in biotechnology and environmental remediation.In recent years, considerable effort has been devoted to finding novel enzyme mimetics with improved catalytic activities. However, the insightful understanding of such catalytic process is still elusive. In this paper, we report for the first time a typical photoactive layer-structured BiOBr as a novel biomimetic catalyst possessing highly efficient intrinsic peroxidase-like activity. Moreover, we have experimentally achieved high dark peroxidase-like catalytic activity in BiOBr microspheres and provided some new insights into the light-enhanced peroxidase-like catalytic property. On the basis of a typical color reaction derived from catalytic oxidation of peroxidase substrates over BiOBr microspheres with H2O2, the simple and sensitive colorimetric assays for detection of H2O2, glucose and

  16. Benzoboroxole-functionalized magnetic core/shell microspheres for highly specific enrichment of glycoproteins under physiological conditions.

    PubMed

    Zhang, Yuting; Ma, Wanfu; Li, Dian; Yu, Meng; Guo, Jia; Wang, Changchun

    2014-04-01

    Efficient enrichment of specific glycoproteins from complex biological samples is of great importance towards the discovery of disease biomarkers in biological systems. Recently, phenylboronic acid-based functional materials have been widely used for enrichment of glycoproteins. However, such enrichment was mainly carried out under alkaline conditions, which is different to the status of glycoproteins in neutral physiological conditions and may cause some unpredictable degradation. In this study, on-demand neutral enrichment of glycoproteins from crude biological samples is accomplished by utilizing the reversible interaction between the cis-diols of glycoproteins and benzoboroxole-functionalized magnetic composite microspheres (Fe3O4/PAA-AOPB). The Fe3O4/PAA-AOPB composite microspheres are deliberately designed and constructed with a high-magnetic-response magnetic supraparticle (MSP) core and a crosslinked poly(acrylic acid) (PAA) shell anchoring abundant benzoboroxole functional groups on the surface. These nanocomposites possessed many merits, such as large enrichment capacity (93.9 mg/g, protein/beads), low non-specific adsorption, quick enrichment process (10 min) and magnetic separation speed (20 s), and high recovery efficiency. Furthermore, the as-prepared Fe3O4/PAA-AOPB microspheres display high selectivity to glycoproteins even in the E. coli lysate or fetal bovine serum, showing great potential in the identify of low-abundance glycoproteins as biomarkers in real complex biological systems for clinical diagnoses.

  17. Development and characterization of fast responding pressure sensitive microspheres.

    PubMed

    Kimura, Fletcher; Rodriguez, Miguel; McCann, Jesse; Carlson, Brenden; Dabiri, Dana; Khalil, Gamal E; Callis, James B; Xia, Younan; Gouterman, Martin

    2008-07-01

    The response times of pressure sensitive paint (PSP) and pressure sensitive microspheres to passing shockwaves were measured to investigate their ability to accurately determine pressure changes in unsteady flows. The PSPs tested used platinum tetra(pentafluorophenyl)porphine (PtTFPP), platinum octaethylporphine (PtOEP), and a novel set of osmium-based organometallic complexes as pressure sensitive luminophors incorporated into polymer matrices of dimethylsiloxane bisphenol A-polycarbonate block copolymer or polystyrene. Two types of pressure sensitive microspheres were used, the first being PtOEP-doped polystyrene microspheres (PSBeads) and the second being porous silicon dioxide microspheres containing the novel, pressure sensitive osmium complexes. Response times for the platinum-based PSPs ranged from 47.2 to 53.0 micros, while the osmium-based PSPs ranged between 37.6 and 58.9 micros. For the microspheres, 2.5 microm diameter PSBeads showed a response time of 3.15 ms, while the osmium-based silicon dioxide microspheres showed a response time ranging between 13.6 and 18.9 micros.

  18. Fractionating Polymer Microspheres as Highly Accurate Density Standards.

    PubMed

    Bloxham, William H; Hennek, Jonathan W; Kumar, Ashok A; Whitesides, George M

    2015-07-21

    This paper describes a method of isolating small, highly accurate density-standard beads and characterizing their densities using accurate and experimentally traceable techniques. Density standards have a variety of applications, including the characterization of density gradients, which are used to separate objects in a variety of fields. Glass density-standard beads can be very accurate (±0.0001 g cm(-3)) but are too large (3-7 mm in diameter) for many applications. When smaller density standards are needed, commercial polymer microspheres are often used. These microspheres have standard deviations in density ranging from 0.006 to 0.021 g cm(-3); these distributions in density make these microspheres impractical for applications demanding small steps in density. In this paper, commercial microspheres are fractionated using aqueous multiphase systems (AMPS), aqueous mixture of polymers and salts that spontaneously separate into phases having molecularly sharp steps in density, to isolate microspheres having much narrower distributions in density (standard deviations from 0.0003 to 0.0008 g cm(-3)) than the original microspheres. By reducing the heterogeneity in densities, this method reduces the uncertainty in the density of any specific bead and, therefore, improves the accuracy within the limits of the calibration standards used to characterize the distributions in density.

  19. Imaging of drug loading distributions in individual microspheres of calcium silicate hydrate--an X-ray spectromicroscopy study.

    PubMed

    Guo, Xiaoxuan; Wang, Zhiqiang; Wu, Jin; Wang, Jian; Zhu, Ying-Jie; Sham, Tsun-Kong

    2015-04-21

    Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere.

  20. One pot preparation of silver nanoparticles decorated TiO2 mesoporous microspheres with enhanced antibacterial activity.

    PubMed

    Chen, Yuemei; Deng, Yuanming; Pu, Yitao; Tang, Bijun; Su, Yikun; Tang, Jiaoning

    2016-08-01

    We report a simple "one-pot" solvothermal preparation of silver nanoparticles (Ag NPs) decorated mesoporous titania (TiO2) microspheres as an effective antibacterial agent. TBOT as Ti source was hydrolyzed and crystallized in media composed of acetic acid and ethanol, in which esterification catalyzed by TBOT occurred for in-situ "controlled water release". AgNO3 as Ag source was reduced by ethanol to form Ag NPs embedded in the TiO2 microspheres. The effect of AgNO3 and HAc on the morphology of Ag/TiO2 was investigated. The Ag/TiO2 with various Ag content showed excellent antibacterial activities with extremely low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Escherichia coli and Staphylococcus aureus when compared with colloidal Ag NPs. PMID:27157724

  1. Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate.

    PubMed

    Anande, Nalini M; Jain, Sunil K; Jain, Narendra K

    2008-07-01

    The aim of the research work was to develop cyst-targeted novel concanavalin-A (Con-A) conjugated mucoadhesive microspheres of diloxanide furoate (DF) for the effective treatment of amoebiasis. Eudragit microspheres of DF were prepared using emulsification-solvent evaporation method. Formulations were characterized for particle size and size distribution, % drug entrapment, surface morphology and in vitro drug release in simulated gastrointestinal (GI) fluids. Eudragit microspheres of DF were conjugated with Con-A. IR spectroscopy and DSC were used to confirm successful conjugation of Con-A to Eudragit microspheres while Con-A conjugated microspheres were further characterized using the parameters of zeta potential, mucoadhesiveness to colonic mucosa and Con-A conjugation efficiency with microspheres. IR studies confirmed the attachment of Con-A with Eudragit microspheres. All the microsphere formulations showed good % drug entrapment (78+/-5%). Zeta potential of Eudragit microspheres and Con-A conjugated Eudragit microspheres were found to be 3.12+/-0.7mV and 16.12+/-0.5mV, respectively. Attachment of lectin to the Eudragit microspheres significantly increases the mucoadhesiveness and also controls the release of DF in simulated GI fluids. Gamma scintigraphy study suggested that Eudragit S100 coated gelatin capsule retarded the release of Con-A conjugated microspheres at low pH and released microspheres slowly at pH 7.4 in the colon.

  2. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye. PMID:26501994

  3. Microspheres and Nanotechnology for Drug Delivery.

    PubMed

    Jóhannesson, Gauti; Stefánsson, Einar; Loftsson, Thorsteinn

    2016-01-01

    Ocular drug delivery to the posterior segment of the eye can be accomplished by invasive drug injections into different tissues of the eye and noninvasive topical treatment. Invasive treatment involves the risks of surgical trauma and infection, and conventional topical treatments are ineffective in delivering drugs to the posterior segment of the eye. In recent years, nanotechnology has become an ever-increasing part of ocular drug delivery. In the following, we briefly review microspheres and nanotechnology for drug delivery to the eye, including different forms of nanotechnology such as nanoparticles, microparticles, liposomes, microemulsions and micromachines. The permeation barriers and anatomical considerations linked to ocular drug delivery are discussed and a theoretical overview on drug delivery through biological membranes is given. Finally, in vitro, in vivo and human studies of x03B3;-cyclodextrin nanoparticle eyedrop suspensions are discussed as an example of nanotechnology used for drug delivery to the eye.

  4. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  5. Microsphere size influences the foreign body reaction.

    PubMed

    Zandstra, J; Hiemstra, C; Petersen, A H; Zuidema, J; van Beuge, M M; Rodriguez, S; Lathuile, A A; Veldhuis, G J; Steendam, R; Bank, R A; Popa, E R

    2014-01-01

    Biodegradable poly-(DL-lactide-co-glycolide) (PLGA) microspheres (MSP) are attractive candidate vehicles for site-specific or systemic sustained release of therapeutic compounds. This release may be altered by the host's foreign body reaction (FBR), which is dependent on the characteristics of the implant, e.g. chemistry, shape or size. In this study, we focused on the characterisation of the influence of MSP size on the FBR. To this end we injected monodisperse MSP of defined size (small 5.8 µm, coefficient of variance (CV) 14 % and large 29.8 µm, CV 4 %) and polydisperse MSP (average diameter 34.1 µm, CV 51 %) under the skin of rats. MSP implants were retrieved at day 7, 14 and 28 after transplantation. The FBR was studied in terms of macrophage infiltration, implant encapsulation, vascularisation and extracellular matrix deposition. Although PLGA MSP of all different sizes demonstrated excellent in vitro and in vivo biocompatibility, significant differences were found in the characteristics of the FBR. Small MSP were phagocytosed, while large MSP were not. Large MSP occasionally elicited giant cell formation, which was not observed after implantation of small MSP. Cellular and macrophage influx and collagen deposition were increased in small MSP implants compared to large MSP. We conclude that the MSP size influences the FBR and thus might influence clinical outcome when using MSP as a drug delivery device. We propose that a rational choice of MSP size can aid in optimising the therapeutic efficacy of microsphere-based therapies in vivo. PMID:25350249

  6. Effect of Polymer Porosity on Aqueous Self-Healing Encapsulation of Proteins in PLGA Microspheres

    PubMed Central

    Reinhold, Samuel E.

    2014-01-01

    Self-healing (SH) poly(lactic-co-glycolic acid) (PLGA) microspheres are a unique class of functional biomaterials capable of microencapsulating process-sensitive proteins by simple mixing and heating the drug-free polymer in aqueous protein solution. Drug-free SH microspheres of PLGA 50/50 with percolating pore networks of varying porosity (ε = 0.49–73) encapsulate increasing lysozyme (~1–10% w/w) with increasing ε, with typically ~20–25% pores estimated assessible to entry by the enzyme from the external solution. Release kinetics of lysozyme under physiological conditions is continuous over > 2 weeks and most strongly influenced by ε and protein loading before reaching a lag phase until 28 days at the study completion. Recovered enzyme after release is typically predominantly monomeric and active. Formulations containing acid-neutralizing MgCO3 at >4.3% exhibit >97% monomeric and active protein after the release with full mass balance recovery. Hence, control of SH polymer ε is a key parameter to development of this new class of biomaterials. PMID:24285573

  7. Biodiesel production using lipase immobilized on epoxychloropropane-modified Fe3O4 sub-microspheres.

    PubMed

    Zhang, Qian; Zheng, Zhong; Liu, Changxia; Liu, Chunqiao; Tan, Tianwei

    2016-04-01

    Superparamagnetic Fe3O4 sub-microspheres with diameters of approximately 200 nm were prepared via a solvothermal method, and then modified with epoxychloropropane. Lipase was immobilized on the modified sub-microspheres. The immobilized lipase was used in the production of biodiesel fatty acid methyl esters (FAMEs) from acidified waste cooking oil (AWCO). The effects of the reaction conditions on the biodiesel yield were investigated using a combination of response surface methodology and three-level/three-factor Box-Behnken design (BBD). The optimum synthetic conditions, which were identified using Ridge max analysis, were as follows: immobilized lipase:AWCO mass ratio 0.02:1, fatty acid:methanol molar ratio 1:1.10, hexane:AWCO ratio 1.33:1 (mL/g), and temperature 40 °C. A 97.11% yield was obtained under these conditions. The BBD and experimental data showed that the immobilized lipase could generate biodiesel over a wide temperature range, from 0 to 40 °C. Consistently high FAME yields, in excess of 80%, were obtained when the immobilized lipase was reused in six replicate trials at 10 and 20 °C. PMID:26803008

  8. Development of Recombinant Human Growth Hormone (rhGH) sustained-release microspheres by a low temperature aqueous phase/aqueous phase emulsion method.

    PubMed

    Kang, Jian; Wu, Fei; Cai, Yunpeng; Xu, Mingxin; He, Mu; Yuan, Weien

    2014-10-01

    A novel method has been developed to protect Recombinant Human Growth Hormone (rhGH) in poly (lactic-co-glycolic acid) (PLGA) microspheres using an aqueous phase/aqueous phase emulsion and S/O/W multi-emulsion method. This method develops a novel rhGH sustained-release system, which is based on the combination of rhGH-loaded dextran microparticles and PLGA microspheres. The process to fabricate rhGH-loaded dextran microparticles involves an aqueous phase/aqueous phase emulsion system formed at the reduced temperature. RhGH was first dissolved in water together with dextran and polyethylene glycol, followed by stirring at the speed of 2000 rpm for 20-30s at 0°C, and then a freezing process could enable the dextran phase to separate from the continuous PEG phase and rhGH could preferentially be loaded with dextran. The sample after freezing and phase separation was then lyophilized to powder and washed with dichloromethane to remove the PEG. Once loaded in the dextran microparticles (1-4 μm in diameter), rhGH gained resistance to interface tensions and was encapsulated into PLGA microspheres without aggregation thereafter. RhGH released from PLGA microspheres was in a sustained manner with minimal burst and maximally reduced incomplete release in vitro. Single subcutaneous injection of rhGH-loaded PLGA microspheres to rats resulted in a stable plasma concentration for 30 days avoiding the drug concentration fluctuations after multiple injections of protein solutions. In a hypophysectomized rat model, the IGF-1 and bodyweight results showed that there were higher than the levels obtained for the sustained release formulation by W/O/W for 40 days. These results suggest that the microsphere delivery system had the potential to be an injectable depot for sustained-release of the biocompatible protein of rhGH.

  9. Effect of lecithin and MgCO3 as additives on the enzymatic activity of carbonic anhydrase encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres.

    PubMed

    Sandor, Maryellen; Riechel, Alex; Kaplan, Ian; Mathiowitz, Edith

    2002-02-15

    A model enzyme, carbonic anhydrase, was encapsulated and released from poly(lactide-co-glycolide) (PLGA) microspheres (1-3 microm) made by a novel phase inversion technique. Lecithin was used as a surfactant in the encapsulation process and was incorporated in either the organic phase, aqueous phase, both phases, or not at all. Additional microspheres were also made with lecithin incorporated in the aqueous phase and a basic salt, MgCO3, in the polymeric phase. Released carbonic anhydrase, protein extracted from microspheres, or enzyme incubated with lecithin and PLGA were analyzed via HPLC and activity assay to determine the effect of these additives on protein integrity and activity. Lecithin in the aqueous phase appeared to increase the fraction of enzyme in monomeric form as well as its activity for both extracted protein and released protein as compared to the other formulations without MgCO3. Incubation of enzyme with PLGA degradation products indicated that the acidic environment within the microspheres aids in the irreversible inactivation of the encapsulated protein. Addition of MgCO3 further increased the amount of monomer in both the extracted and released protein by decreasing the amount of acid-induced cleavage and noncovalent aggregation, but still greatly decreased the activity of the enzyme. PMID:11960690

  10. Comparative activity of TiO2 microspheres and P25 powder for organic degradation: Implicative importance of structural defects and organic adsorption

    NASA Astrophysics Data System (ADS)

    Wang, Chuan; Liu, Hong; Liu, Yuan; He, Guang'an; Jiang, Chengchun

    2014-11-01

    TiO2 microspheres have been employed as a promisingly new photocatalyst for water and wastewater treatment. P25 TiO2 is commonly employed and its properties are well established as photocatalyst. In this study, photocatalytic activities of the two TiO2 samples are compared by degrading sulfosalicylic acid (SSA), phenol, and 2,4-Dichlorophenoxyacetic acid (2,4-D) under 365 nm UV illumination in a suspension system at neutral pH and associated optimized TiO2 dosages. The results showed that the three organic compounds unexceptionally degraded more rapidly on P25 than on TiO2 microspheres in terms of the concentration-time curves and total organic carbon removals at 120 min. This might me attributed the presence of oxygen vacancies and Ti(III) defects already present on P25 as determined by electron paramagnetic resonance, implying that the defects played an important role for the enhancement of the charge transfer step as rate-determining step. The degradations of three organic compounds on P25 and TiO2 microspheres could be well described by the first-order rate equation, while the degradation kinetics of SSA on TiO2 microspheres was quite different. The difference was ascribed to the medium adsorption ability of SSA on the TiO2 surface.

  11. Effect of surface roughness of chitosan-based microspheres on cell adhesion

    NASA Astrophysics Data System (ADS)

    Zan, Qingfeng; Wang, Chen; Dong, Limin; Cheng, Peng; Tian, Jiemo

    2008-11-01

    Microspheres are novel candidate materials for microcarriers and tissue-engineering scaffolds. Chitosan microspheres were selected as the base materials because of their excellent properties for biomedical applications. But their smooth surfaces were not adapted for cell attachment. Hence, in order to improve the roughness of chitosan microspheres, β-TCP/chitosan composite microspheres were developed. From SEM photographs, the coarse surfaces of composite microspheres were observed, there were some ceramic particles standing out of the chitosan matrix. And their roughness measured by profilometers was about 2.0 μm. Mouse MC3T3-E1 osteoblasts were seeded on the microspheres for evaluating the attachment interaction between cells and materials. According to the ESEM photographs and MTT assay, the adherence and proliferation of osteoblasts on the surfaces of modified microspheres were better than those on the chitosan microspheres, which were mainly attributed to the improved roughness of surface.

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

    PubMed

    Zhao, C; Liu, X D; Nomizu, M; Nishi, N

    2004-05-01

    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.

  13. Encapsulation of catalase in polyelectrolyte microspheres composed of melamine formaldehyde, dextran sulfate, and protamine.

    PubMed

    Balabushevich, N G; Zimina, E P; Larionova, N I

    2004-07-01

    Immobilization of catalase (molecular weight 240,000 daltons) in polyelectrolyte microspheres was studied. The microspheres were obtained by alternating adsorption of dextran sulfate and protamine on commercially available melamine formaldehyde cores followed by the core hydrolysis at pH 1.7. As the interior of the microspheres was filled with homogeneous matrix, the catalase distribution inside the microspheres was uniform. The quantity of entrapped catalase was dependent on the initial concentration of the enzyme and pH of solution, and the peak value was 10(8)-10(9) molecules per microsphere. It was demonstrated that catalase was entrapped in the microspheres via electrostatic and hydrophobic interactions. The catalase activity inside the microspheres increased as the quantity of enzyme decreased, which was due to the switch between diffusion and kinetic regimes of the enzymatic reaction. The microspheres could be applied for separation and concentration of high molecular weight proteins.

  14. Apparatus for washing particulate material. [Removal of silicone oil from microspheres by trichloroethylene

    DOEpatents

    Rivera, A.L.; Fowler, V.L.; Justice, G.V.

    1983-12-29

    Transport of nuclear fuel microspheres through a wash liquid is facilitated by feeding a slurry containing the microspheres into the wash liquid via a column having a vibrating tubular screen located under its lower end.

  15. Mineralization, biodegradation, and drug release behavior of gelatin/apatite composite microspheres for bone regeneration.

    PubMed

    Leeuwenburgh, Sander C G; Jo, Junichiro; Wang, Huanan; Yamamoto, Masaya; Jansen, John A; Tabata, Yasuhiko

    2010-10-11

    Gelatin microspheres are well-known for their capacity to release growth factors in a controlled manner, but gelatin microspheres do not calcify in the absence of so-called bioactive substances that induce deposition of calcium phosphate (CaP) bone mineral. This study has investigated if CaP nanocrystals can be incorporated into gelatin microspheres to render these inert microspheres bioactive without compromising the drug releasing properties of gelatin microspheres. Incorporation of CaP nanocrystals into gelatin microspheres resulted into reduced biodegradation and drug release rates, whereas their calcifying capacity increased strongly compared to inert gelatin microspheres. The reduced drug release rate was correlated to the reduced degradation rate as caused by a physical cross-linking effect of CaP nanocrystals dispersed in the gelatin matrix. Consequently, these composite microspheres combine beneficial drug-releasing properties of organic gelatin with the calcifying capacity of a dispersed CaP phase. PMID:20804200

  16. Physicochemical characterization of camptothecin membrane binding properties and polymeric microsphere formulations

    NASA Astrophysics Data System (ADS)

    Selvi, Bilge

    acidic media CPT-loaded microspheres were prepared in a 10 N HCl-methylene chloride mixture using the H-series of poly(D,L-lactide-co-glycolide) (H-PLGA). The system was then compared with a standard microsphere formation method and the results were evaluated with respect to particle morphology and drug release profile. Rough surface of the particles were obtained from the preparation method where a 10 N HCl solution was used. The release pattern of CPT was biphasic comprising a first burst effect followed by zero order release for all the formulations. However, the release of the drug was slightly faster from the microspheres formed with the modified method compared to the standard. Until now clinical application of CPT has been highly restricted by the insolubility and instability of the drug in its active lactone form, resulting in less antitumor potency and poor bioavailability. The pH-dependent release of the CPT-loaded microspheres was also compared and faster initial release (burst phase) was found at neutral pH, whereas at low pH the release was zero order for all the formulations. The results indicate that the stabilization and sustained release of CPT from H-PLGA microspheres might reduce local toxicity while simultaneously prolonging efficiency, suggesting new perspectives in CPT chemotherapy.

  17. Three dimensional confocal microscopy of fluorescent microspheres: imaging and size determination

    NASA Astrophysics Data System (ADS)

    Rakovich, Y. P.; Yang, L.; Taylor, C. M.; Dunbar, L. A.; Mac Raighne, Aaron; Donegan, J. F.; McCabe, Eithne M.

    2005-06-01

    In this paper, we experimentally studied both the bright-field and fluorescence images of microspheres by conventional and confocal scanning polarization microscopes. A qualitative analysis have been given to show a physical picture on the imaging of the microspheres. Emission spectra from melamine formaldehyde microspheres stained with Ethidium Bromide or covered by thin shell of CdTe nanocrystals have been experimentally studied. We adopted analytical expressions describing the resonance spacing in order to determine the size of the microspheres.

  18. Microencapsulation of bacteriophage felix O1 into chitosan-alginate microspheres for oral delivery.

    PubMed

    Ma, Yongsheng; Pacan, Jennifer C; Wang, Qi; Xu, Yongping; Huang, Xiaoqing; Korenevsky, Anton; Sabour, Parviz M

    2008-08-01

    This paper reports the development of microencapsulated bacteriophage Felix O1 for oral delivery using a chitosan-alginate-CaCl(2) system. In vitro studies were used to determine the effects of simulated gastric fluid (SGF) and bile salts on the viability of free and encapsulated phage. Free phage Felix O1 was found to be extremely sensitive to acidic environments and was not detectable after a 5-min exposure to pHs below 3.7. In contrast, the number of microencapsulated phage decreased by 0.67 log units only, even at pH 2.4, for the same period of incubation. The viable count of microencapsulated phage decreased only 2.58 log units during a 1-h exposure to SGF with pepsin at pH 2.4. After 3 h of incubation in 1 and 2% bile solutions, the free phage count decreased by 1.29 and 1.67 log units, respectively, while the viability of encapsulated phage was fully maintained. Encapsulated phage was completely released from the microspheres upon exposure to simulated intestinal fluid (pH 6.8) within 6 h. The encapsulated phage in wet microspheres retained full viability when stored at 4 degrees C for the duration of the testing period (6 weeks). With the use of trehalose as a stabilizing agent, the microencapsulated phage in dried form had a 12.6% survival rate after storage for 6 weeks. The current encapsulation technique enables a large proportion of bacteriophage Felix O1 to remain bioactive in a simulated gastrointestinal tract environment, which indicates that these microspheres may facilitate delivery of therapeutic phage to the gut. PMID:18515488

  19. PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

    PubMed

    Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

    2015-08-01

    In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the

  20. In situ one-pot preparation of superparamagnetic hydrophilic porous microspheres for covalently immobilizing penicillin G acylase to synthesize amoxicillin

    NASA Astrophysics Data System (ADS)

    Xue, Ping; Gu, Yaohua; Su, Weiguang; Shuai, Huihui; Wang, Julan

    2016-01-01

    Magnetic hydrophilic porous microspheres were successfully one-pot synthesized for the first time via in situ inverse suspension polymerization of glycidyl methacrylate, N,N‧-methylene bisacrylamide and 2-hydroxyethyl methacrylate in the presence of Fe3+ and Fe2+ dispersed in formamide, which were denoted as magnetic Fe3O4-GMH microspheres. The morphology and properties of magnetic Fe3O4-GMH microspheres were characterized by SEM, VSM, XRD, FTIR, and so on. The formamide content had an important influence on the morphology of Fe3O4-GMH, and nearly perfectly spherical Fe3O4-GMH particles were formed when the amount of formamide was 15 ml. The diameters of the microspheres were in the range of 100-200 μm and Fe3O4-GMH exhibited superparamagnetic behavior with the saturation magnetization of 5.44 emu/g. The specific surface area of microspheres was 138.7 m2/g, the average pore diameter and pore volume were 15.1 nm and 0.60 cm3/g, respectively. The content of oxirane groups on Fe3O4-GMH was 0.40 mmol/g. After penicillin G acylase (PGA) was covalently immobilized on Fe3O4-GMH microspheres, the catalytic performance for amoxicillin synthesis by 6-aminopenicillanic acid and D-hydroxyphenylglycine methyl ester was largely improved. As a result, 90.1% amoxicillin yield and 1.18 of the synthesis/hydrolysis (S/H) ratio were achieved on PGA/Fe3O4-GMH with ethylene glycol as solvent, but only 62.6% amoxicillin yield and 0.37 of the S/H ratio were obtained on free PGA under the same reaction conditions. Furthermore, the amoxicillin yield and S/H ratio were still kept at 88.2% and 1.06, respectively after the immobilized PGA was magnetically separated and recycled for 10 times, indicating that PGA/Fe3O4-GMH had a very good reusability.

  1. Tetracycline-HCl-loaded poly(DL-lactide-co-glycolide) microspheres prepared by a spray drying technique: influence of gamma-irradiation on radical formation and polymer degradation.

    PubMed

    Bittner, B; Mäder, K; Kroll, C; Borchert, H H; Kissel, T

    1999-05-01

    produced hydrophilic spin adducts of PBN and monomeric radicals of lactic or glycolic acid. These degradation products were not detected by EPR. This result is confirmed by the observation that possible diamagnetic reaction products of low molecular weight, consisting of TEMPOL and lactide or glycolide monomers, could not be detected by GC-MS. While an irradiation dose-dependent decrease in molecular weight of PLGA could be verified in agreement with the literature, TCH content of the microspheres was not affected by the exposure to gamma-rays. It can be concluded that EPR spectroscopy in combination with GPC, DSC, and HPLC allows a detailed characterization of the impact of gamma-sterilization on biodegradable parenteral drug delivery systems. PMID:10210719

  2. Mixed uranium dicarbide and uranium dioxide microspheres and process of making same

    DOEpatents

    Stinton, David P.

    1983-01-01

    Nuclear fuel microspheres are made by sintering microspheres containing uranium dioxide and uncombined carbon in a 1 mole percent carbon monoxide/99 mole percent argon atmosphere at 1550.degree. C. and then sintering the microspheres in a 3 mole percent carbon monoxide/97 mole percent argon atmosphere at the same temperature.

  3. Novel hollow Pt-ZnO nanocomposite microspheres with hierarchical structure and enhanced photocatalytic activity and stability

    NASA Astrophysics Data System (ADS)

    Yu, Changlin; Yang, Kai; Xie, Yu; Fan, Qizhe; Yu, Jimmy C.; Shu, Qing; Wang, Chunying

    2013-02-01

    Noble metal/semiconductor nanocomposites play an important role in high efficient photocatalysis. Herein, we demonstrate a facile strategy for fabrication of hollow Pt-ZnO nanocomposite microspheres with hierarchical structure under mild solvothermal conditions using Zn (CH3COO)2.2H2O and HPtCl4 as the precursors, and polyethylene glycol-6000 (PEG-6000) and ethylene glycol as the reducing agent and solvent, respectively. The as-synthesized ZnO and Pt-ZnO composite nanocrystals were well characterized by powder X-ray diffraction (XRD), nitrogen-physical adsorption, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectra (DRS), and photoluminescence (PL) emission spectroscopy. It was found that Pt content greatly influences the morphology of Pt-ZnO composite nanocrystals. Suitable concentration of HPtCl4 in the reaction solution system can produce well hierarchically hollow Pt-ZnO nanocomposite microspheres, which are composed of an assembly of fine Pt-ZnO nanocrystals. Photocatalytic tests of the Pt-ZnO microspheres for the degradation of the dye acid orange II revealed extremely high photocatalytic activity and stability compared with those of pure ZnO and corresponding Pt deposited ZnO. The remarkable photocatalytic performance of hollow Pt-ZnO microspheres mainly originated from their unique nanostructures and the low recombination rate of the e-/h+ pairs by the platinum nanoparticles embedded in ZnO nanocrystals.Noble metal/semiconductor nanocomposites play an important role in high efficient photocatalysis. Herein, we demonstrate a facile strategy for fabrication of hollow Pt-ZnO nanocomposite microspheres with hierarchical structure under mild solvothermal conditions using Zn (CH3COO)2.2H2O and HPtCl4 as the precursors, and polyethylene glycol-6000 (PEG-6000) and ethylene glycol as the reducing agent and solvent, respectively. The as

  4. Thermal expansion of an epoxy-glass microsphere composite

    NASA Technical Reports Server (NTRS)

    Price, H. L.; Burks, H. D.

    1977-01-01

    The thermal expansion of a composite of epoxy (diglycidyl ether of bisphenol A) and solid glass microspheres was investigated. The microspheres had surfaces which were either untreated or treated with a silicone release agent, an epoxy coupling agent, or a general purpose silane coupling agent. Both room temperature (about 300 K) and elevated temperature (about 475 K) cures were used for the epoxy. Two microsphere size ranges were used, about 50 microns, which is applicable in filled moldings, and about 125 microns, which is applicable as bond line spacers. The thermal expansion of the composites was measured from 300 to 350 K or from 300 to 500 K, depending on the epoxy cure temperature. Measurements were made on composites containing up to .6 volume fraction microspheres. Two predictive models, which required only the values of thermal expansion of the polymer and glass and their specific gravities, were tested against the experimental data. A finite element analysis was made of the thermal strain of a composite cell containing a single microsphere surrounded by a finite-thickness interface.

  5. Iron Nanoparticles-Encapsulating Silica Microspheres for Arterial Embolization Hyperthermia

    NASA Astrophysics Data System (ADS)

    Li, Z.; Kawashita, M.

    2011-10-01

    We attempted to prepare α-Fe-encapsulating silica (αFeSi) microspheres by a sol-gel process using tetramethoxysilane (TMOS) in water-in-oil emulsion. The effect of preparation conditions on the structure, magnetic and heating properties of resultant products were investigated. Oil phase consisted of kerosene with 32 wt% of surfactants (sorbitan monooleate / sorbitan monostearate in 3:1 weight ratio). Water phase consisted of TMOS, ethanol (CH2CH3OH), water and iron nitrate (Fe(NO3)3·9H2O) with TMOS / CH2CH3OH/H2O/Fe3+ in 1:7.4:16.2:0.4~1.2 molar ratio. Fe3+-containing silica gel (FeSiG) microspheres 5 to 30 μm in size were successfully obtained by adding the water phase into the oil phase at 60 °C under stirring of 1500 rpm for 100 min. αFeSi microspheres was obtained by heating the FeSiG microspheres at 850°C in argon atmosphere. The obtained αFeSi microspheres have a saturation magnetization (Ms) up to 21 emu g-1 and a coercive force (Hc) of 133 Oe. The in vitro heating generation was evaluated under an alternating current (AC) magnetic field of 300 Oe and 100 kHz.

  6. Modelling heating of liver tumours with heterogeneous magnetic microsphere deposition.

    PubMed

    Tsafnat, N; Tsafnat, G; Lambert, T D; Jones, S K

    2005-06-21

    Ferromagnetic embolization hyperthermia (FEH) is a novel treatment for liver cancer. Magnetic microspheres are injected into the hepatic artery and cluster in the periphery of tumours and are heated with externally applied magnetic fields. In order to more accurately simulate FEH, we modelled a three-dimensional heterogeneous distribution of heat sources. We constructed a fractal model of the vasculature in the periphery of a tumour. We used this model to compute the spatial distribution of the microspheres that lodge in capillaries. We used the distribution model as input to a finite-element heat transfer model of the FEH treatment. The overall appearance of the vascular tree is subjectively similar to that of the disorganized vascular network which encapsulates tumours. The microspheres are distributed in the tumour periphery in similar patterns to experimental observations. We expect the vasculature and microsphere deposition models to also be of interest to researchers of any targeted cancer therapies such as localized intra-arterial chemotherapy and selective internal radiotherapy. Our results show that heterogeneous microsphere distributions give significantly different results to those for a homogeneous model and thus are preferable when accurate results are required.

  7. Modelling heating of liver tumours with heterogeneous magnetic microsphere deposition

    NASA Astrophysics Data System (ADS)

    Tsafnat, N.; Tsafnat, G.; Lambert, T. D.; Jones, S. K.

    2005-06-01

    Ferromagnetic embolization hyperthermia (FEH) is a novel treatment for liver cancer. Magnetic microspheres are injected into the hepatic artery and cluster in the periphery of tumours and are heated with externally applied magnetic fields. In order to more accurately simulate FEH, we modelled a three-dimensional heterogeneous distribution of heat sources. We constructed a fractal model of the vasculature in the periphery of a tumour. We used this model to compute the spatial distribution of the microspheres that lodge in capillaries. We used the distribution model as input to a finite-element heat transfer model of the FEH treatment. The overall appearance of the vascular tree is subjectively similar to that of the disorganized vascular network which encapsulates tumours. The microspheres are distributed in the tumour periphery in similar patterns to experimental observations. We expect the vasculature and microsphere deposition models to also be of interest to researchers of any targeted cancer therapies such as localized intra-arterial chemotherapy and selective internal radiotherapy. Our results show that heterogeneous microsphere distributions give significantly different results to those for a homogeneous model and thus are preferable when accurate results are required.

  8. Controlling silk fibroin microspheres via molecular weight distribution.

    PubMed

    Zeng, Dong-Mei; Pan, Jue-Jing; Wang, Qun; Liu, Xin-Fang; Wang, Hui; Zhang, Ke-Qin

    2015-05-01

    Silk fibroin (SF) microspheres were produced by salting out SF solution via the addition of potassium phosphate buffer solution (K2HPO4-KH2PO4). The morphology, size and polydispersity of SF microspheres were adjusted by changing the molecular weight (MW) distribution and concentration of SF, as well as the ionic strength and pH of the buffer solution. Changing the conditions under which the SF fiber dissolved in the Lithium Boride (LiBr) solution resulted in altering the MW distribution of SF solution. Under optimal salting-out conditions (ionic strength>0.7 M and pH>7) and using a smaller and narrower SF MW distribution, SF microspheres with smoother shapes and more uniform sizes were produced. Meanwhile, the size and polydispersity of the microspheres increased when the SF concentration was increased from 0.25 mg/mL to 20 mg/mL. The improved SF microspheres, obtained by altering the distribution of molecular weight, have potential in drug and gene delivery applications.

  9. Poly(ester amide) blend microspheres for oral insulin delivery.

    PubMed

    He, Pan; Liu, Huaiyu; Tang, Zhaohui; Deng, Mingxiao; Yang, Yan; Pang, Xuan; Chen, Xuesi

    2013-10-15

    This study developed a novel oral insulin formulation centered on microspheres consisting of a blend of biodegradable poly(ester amide) (PEA). In the formulation, L-lysine-/L-leucine-based PEA with pendant COOH groups (PEA-COOH) was used as a pH-responsive material for the protection of insulin from the harsh environmental conditions of the stomach. Arginine-based PEA (Arg-PEA) was introduced to improve the intestinal absorption of the drug. The influence of both the hydrophobicity of PEA-COOH and the content of Arg-PEA was investigated in detail on microsphere surface morphology, drug loading, and the in vitro release profile of insulin. The PEA-COOH/Arg-PEA blend microspheres protected the loaded insulin in simulated gastric fluid and released insulin in a fast and sustained manner in simulated intestinal fluid. The in vivo test demonstrated that the oral administration of insulin-loaded PEA blend microspheres could effectively suppress the blood glucose level in diabetic rats for 10h, and the oral bioavailability was improved to 5.89+1.84% in healthy rats. These results indicate that the PEA blend microspheres are promising vehicles for the oral delivery of insulin.

  10. Pharmacodynamics of diclofenac from novel Eudragit entrapped microspheres.

    PubMed

    Momoh, M A; Kenechukwu, F C; Adedokun, M O; Odo, C E; Attama, A A

    2014-05-01

    Effective clinical utilization of non-steroidal anti-inflammatory drugs such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration, thus necessitating the need for a better carrier to minimize these obvious limitations. The objective of this study was to evaluate Eudragit® RS100/RL100 microspheres formulated by the solvent-evaporation technique for improved delivery of diclofenac. Three batches of (DF1, DF2 and DF3) microspheres were prepared using different ratios of Eudragit RS-100 and RL-100 polymers based on the solvent-evaporation method. The microspheres were characterized based on morphological properties, particle size analysis and encapsulation efficiency (EE%). In vitro release of DS was investigated in both 0.1 N HCl (pH 1.2) and phosphate-buffered saline (pH 7.4), while anti-inflammatory studies were evaluated in the rat model. Maximum EE% of 86.61 ± 0.11, 88.14 ± 0.16 and 85.50 ± 0.21 was obtained for DF1, DF2 and DF3, respectively. Discrete, smooth and brownish microspheres of size range 437 ± 0.01-479 ± 0.21 µm were obtained. Release of DS from the formulation depends on the polymer ratio. All the batches exhibited good anti-inflammatory activities. Microsphere formulations based on Eudragit® polymers would likely offer a reliable and alternative means of delivering DS orally.

  11. Surface characterization by atomic force microscopy of sterilized PLGA microspheres.

    PubMed

    Dorati, Rossella; Patrini, Maddalena; Perugini, Paola; Pavanetto, Franca; Stella, Angiolino; Modena, Tiziana; Genta, Ida; Conti, Bice

    2006-03-01

    Atomic force microscopy (AFM) is recognized a suitable and powerful technique for surface and morphological analysis. Even if until now this technique has not been frequently used in the pharmaceutical field, it can contribute to an accurate morphologic characterization of microspheres and nanospheres. In this work, atomic force microscopy has been used to perform the surface characterization of sterilized microspheres. The aim is to investigate the morphologic modifications induced by gamma irradiation on poly(lactide-co-glycolide) microspheres loaded with ovalbumin and to compare the results obtained by AFM to those obtained by scanning electron microscopy (SEM). The results obtained show that, with respect to SEM, AFM can give some additional information regarding the modifications induced by gamma-irradiation on microspheres surface morphology. The significant changes in surface roughness after irradiation are indicative of damage due to gamma-irradiation. The unchanged surface roughness values calculated for microspheres containing PEG in their matrix, suggest that this polymer exerts a protective effect towards gamma-irradiation. PMID:16754370

  12. Solvent/Non-Solvent Sintering To Make Microsphere Scaffolds

    NASA Technical Reports Server (NTRS)

    Laurencin, Cato T.; Brown, Justin L.; Nair, Lakshmi

    2011-01-01

    A solvent/non-solvent sintering technique has been devised for joining polymeric microspheres to make porous matrices for use as drug-delivery devices or scaffolds that could be seeded with cells for growing tissues. Unlike traditional sintering at elevated temperature and pressure, this technique is practiced at room temperature and pressure and, therefore, does not cause thermal degradation of any drug, protein, or other biochemical with which the microspheres might be loaded to impart properties desired in a specific application. Also, properties of scaffolds made by this technique are more reproducible than are properties of comparable scaffolds made by traditional sintering. The technique involves the use of two miscible organic liquids: one that is and one that is not a solvent for the affected polymer. The polymeric microspheres are placed in a mold having the size and shape of the desired scaffold, then the solvent/non-solvent mixture is poured into the mold to fill the void volume between the microspheres, then the liquid mixture is allowed to evaporate. Some of the properties of the resulting scaffold can be tailored through choice of the proportions of the liquids and the diameter of the microspheres.

  13. Amino-functionalized core-shell magnetic mesoporous composite microspheres for Pb(II) and Cd(II) removal.

    PubMed

    Tang, Yulin; Liang, Song; Wang, Juntao; Yu, Shuili; Wang, Yilong

    2013-04-01

    Amino-functionalized Fe3O4@mesoporous SiO2 core-shell composite microspheres NH2-MS in created in multiple synthesis steps have been investigated for Pb(II) and Cd(II) adsorption. The microspheres were characterized by transmission electron microscope (TEM), scanning electron microscope (SEM), N2 adsorption-desorption, zeta potential measurements and vibrating sample magnetometer. Batch adsorption tests indicated that NH2-MS exhibited higher adsorption affinity toward Pb(II) and Cd(II) than MS did. The Langmuir model could fit the adsorption isotherm very well with maximum adsorption capacity of 128.21 and 51.81 mg/g for Pb(II) and Cd(II), respectively, implying that adsorption processes involved monolayer adsorption. Pb(II) and Cd(II) adsorption could be well described by the pseudo second-order kinetics model, and was found to be strongly dependent on pH and humic acid. The Pb(II)- and Cd(II)-loaded microspheres were effectively desorbed using 0.01 mol/L HCl or EDTA solution. NH2-MS have promise for use as adsorbents in the removal of Pb(II) and Cd(II) in wastewater treatment processes. PMID:23923794

  14. Hierarchical {001}-faceted BiOBr microspheres as a novel biomimetic catalyst: dark catalysis towards colorimetric biosensing and pollutant degradation.

    PubMed

    Li, Lili; Ai, Lunhong; Zhang, Caihong; Jiang, Jing

    2014-05-01

    In recent years, considerable effort has been devoted to finding novel enzyme mimetics with improved catalytic activities. However, the insightful understanding of such catalytic process is still elusive. In this paper, we report for the first time a typical photoactive layer-structured BiOBr as a novel biomimetic catalyst possessing highly efficient intrinsic peroxidase-like activity. Moreover, we have experimentally achieved high dark peroxidase-like catalytic activity in BiOBr microspheres and provided some new insights into the light-enhanced peroxidase-like catalytic property. On the basis of a typical color reaction derived from catalytic oxidation of peroxidase substrates over BiOBr microspheres with H2O2, the simple and sensitive colorimetric assays for detection of H2O2, glucose and ascorbic acid were successfully established. More interestingly, the BiOBr microspheres showed strong ability towards activation of H2O2, displaying excellent dark catalytic activity for the degradation of organic dye. It is therefore believed that our findings in this study could open up the possibility of utilizing BiOBr as enzymatic mimics in biotechnology and environmental remediation. PMID:24637562

  15. Synthesis of hydrophilic intra-articular microspheres conjugated to ibuprofen and evaluation of anti-inflammatory activity on articular explants.

    PubMed

    Bédouet, Laurent; Moine, Laurence; Pascale, Florentina; Nguyen, Van-Nga; Labarre, Denis; Laurent, Alexandre

    2014-01-01

    The main limitation of current microspheres for intra-articular delivery of non-steroidal anti-inflammatory drugs (NSAIDs) is a significant initial burst release, which prevents a long-term drug delivery. In order to get a sustained delivery of NSAIDs without burst, hydrogel degradable microspheres were prepared by co-polymerization of a methacrylic derivative of ibuprofen with oligo(ethylene-glycol) methacrylate and poly(PLGA-PEG) dimethacrylate as degradable crosslinker. Microspheres (40-100 μm) gave a low yield of ibuprofen release in saline buffer (≈2% after 3 months). Mass spectrometry analysis confirmed that intact ibuprofen was regenerated indicating that ester hydrolysis occurred at the carboxylic acid position of ibuprofen. Dialysis of release medium followed by alkaline hydrolysis show that in saline buffer ester hydrolysis occurred at other positions in the polymer matrix leading to the release of water-soluble polymers (>6-8000 Da) conjugated with ibuprofen showing that degradation and drug release are simultaneous. By considering the free and conjugated ibuprofen, 13% of the drug is released in 3 months. In vitro, ibuprofen-loaded MS inhibited the synthesis of prostaglandin E2 in articular cartilage and capsule explants challenged with lipopolysaccharides. Covalent attachment of ibuprofen to PEG-hydrogel MS suppresses the burst release and allows a slow drug delivery for months and the cyclooxygenase-inhibition property of regenerated ibuprofen is preserved.

  16. Ex vivo human trabecular bone model for biocompatibility evaluation of calcium phosphate composites modified with spray dried biodegradable microspheres.

    PubMed

    Schnieders, Julia; Gbureck, Uwe; Germershaus, Oliver; Kratz, Marita; Jones, David B; Kissel, Thomas

    2013-10-01

    Our aim was to study the suitability of the ex-vivo human trabecular bone bioreactor ZetOS to test the biocompatibility of calcium phosphate bone cement composites modified with spray dried, drug loaded microspheres. We hypothesized, that this bone bioreactor could be a promising alternative to in vivo assessment of biocompatibility in living human bone over a defined time period. Composites consisting of tetracycline loaded poly(lactic-co-glycolic acid) microspheres and calcium phosphate bone cement, were inserted into in vitro cultured human femora head trabecular bone and incubated over 30 days at 37°C in the incubation system. Different biocompatibility parameters, such as lactate dehydrogenase activity, alkaline phosphatase release and the expression of relevant cytokines, IL-1β, IL-6, and TNF-α, were measured in the incubation medium. No significant differences in alkaline phosphatase, osteocalcin, and lactate dehydrogenase activity were measured compared to control samples. Tetracycline was released from the microspheres, delivered and incorporated into newly formed bone. In this study we demonstrated that ex vivo biocompatibility testing using human trabecular bone in a bioreactor is a potential alternative to animal experiments since bone metabolism is still maintained in a physiological environment ex vivo.

  17. Hydrothermal synthesis of NiS nanobelts and NiS{sub 2} microspheres constructed of cuboids architectures

    SciTech Connect

    Wang Lili; Zhu Yongchun; Li Haibo; Li Qianwen; Qian Yitai

    2010-01-15

    NiS nanobelts of hexagonal phase have been hydrothermally synthesized starting from Ni(CH{sub 3}COO){sub 2}.4H{sub 2}O and Na{sub 2}S{sub 2}O{sub 3}.5H{sub 2}O at 200 deg. C for 12 h. The as-prepared nanobelts were 50 nm thick, 70-200 nm wide and more than 10 {mu}m long. As ethylenediaminetetraacetic acid (EDTA) added, in similar condition, 2 {mu}m NiS{sub 2} microspheres of cubic phase were prepared. However, as Ni{sup 2+}/S{sub 2}O{sub 3}{sup 2-} ratio was 1:1 and the temperature was decreased to 160 deg. C, 5 {mu}m NiS{sub 2} microspheres constructed of cuboids were formed. - Graphical abstract: Hexagonal NiS nanobelts and cubic NiS{sub 2} microspheres were hydrothermally synthesized in the reaction of Ni(CH{sub 3}COO){sub 2}.4H{sub 2}O and Na{sub 2}S{sub 2}O{sub 3}.5H{sub 2}O.

  18. Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

    PubMed Central

    Ye, Zhuo; Ji, Yan-Li; Ma, Xiang; Wen, Jian-Guo; Wei, Wei; Huang, Shu-Man

    2015-01-01

    AIM To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid) (PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form. METHODS Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection. RESULTS The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form. CONCLUSION The result of this study

  19. An in-vitro evaluation of three types of drug-eluting microspheres loaded with irinotecan.

    PubMed

    Pereira, Philippe L; Plotkin, Stephen; Yu, Renee; Sutter, Allison; Wu, Yue; Sommer, Christof M; Cruise, Gregory M

    2016-10-01

    To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100-300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified using validated high-performance liquid chromatography methods. In-vitro elution was performed over 24 h using a USP 4 dissolution apparatus. Diameter measurements were performed using light microscopy. Time in suspension was considered as the time required for the microspheres to vacate 1/3 of the volume. All three microsphere types rapidly loaded irinotecan, with more than 95% loading at 1 h. In-vitro elution of irinotecan was rapid for LifePearl and DC Bead microspheres, with more than 98% elution at 1 h, and delayed for Tandem microspheres, with about 70% elution at 6 h. After loading with irinotecan, the average diameter of LifePearl and DC Bead microspheres was reduced by 9 and 18%, respectively, and was unchanged for Tandem microspheres. All three microsphere types lost 4-6% of the loaded irinotecan almost immediately upon placement in contrast: water and contrast: 5% dextrose, but further losses were minimal over 2 weeks. LifePearl microspheres remained longer in suspension (392±23 s) compared with DC Bead (154±13 s, P<0.001) and Tandem (198±19 s, P<0.001) microspheres. All three microsphere types lo