Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

PubMed Central

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-01-01

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. PMID:28398222

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

PubMed

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-04-11

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly( γ -glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca 2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

Lactobacillus casei Encapsulated in Soy Protein Isolate and Alginate Microparticles Prepared by Spray Drying

PubMed Central

2017-01-01

Summary This article presents a novel formulation for preparation of Lactobacillus casei 01 encapsulated in soy protein isolate and alginate microparticles using spray drying method. A response surface methodology was used to optimise the formulation and the central composite face-centered design was applied to study the effects of critical material attributes and process parameters on viability of the probiotic after microencapsulation and in simulated gastrointestinal conditions. Spherical microparticles were produced in high yield (64%), narrow size distribution (d50=9.7 µm, span=0.47) and favourable mucoadhesive properties, with viability of the probiotic of 11.67, 10.05, 9.47 and 9.20 log CFU/g after microencapsulation, 3 h in simulated gastric and intestinal conditions and four-month cold storage, respectively. Fourier-transform infrared spectroscopy confirmed the probiotic stability after microencapsulation, while differential scanning calorimetry and thermogravimetry pointed to high thermal stability of the soy protein isolate-alginate microparticles with encapsulated probiotic. These favourable properties of the probiotic microparticles make them suitable for incorporation into functional food or pharmaceutical products. PMID:28867947

Design and characterization of emulsified spray dried alginate microparticles as a carrier for the dually acting drug roflumilast.

PubMed

Mahmoud, Azza A; Elkasabgy, Nermeen A; Abdelkhalek, Abdel Fatah A

2018-06-18

Roflumilast is a selective inhibitor of phosphodiesterase-4 isoenzyme in lung cells. Having psychiatric adverse reactions when administered orally affects negatively the patients' adherence to the drug. This work aimed to prepare emulsified spray dried alginate microparticles for the pulmonary delivery of roflumilast. Sodium alginate was used as microparticle-forming material, isopropyl myristate as an oil, Tween®80 as surfactant and calcium beta-glycerophosphate as cross-linking agent to enhance the mechanical properties of the particles. The prepared particles were evaluated for their encapsulation efficiency, particle size and in-vitro release. From the studied carriers, beta-cyclodextrin (CD) was the best regarding giving formulation smaller particle size and more sustained drug release. The inhalation profile of CD-based microparticles was investigated using Anderson cascade impactor. The aerosolization profile of CD-based microparticles suggested their efficiency to deliver the drug deep in the lung. The CD-based microparticles possessed more inhibitory effects on the viability of A549 cells and on the pro-inflammatory cytokines (TNF-α, IL-6 and IL-10) compared to the pure drug. Hence, CD-based microparticles could regulate the tumorigenesis besides tumor-associated inflammation. Finally, CD-based microparticles showed more sustained bronchodilatation properties in healthy human volunteers when compared to Ventolin®HFA. CD-based microparticles proved to be a promising carrier for inhaled roflumilast in human. Copyright © 2018. Published by Elsevier B.V.

Smart swelling biopolymer microparticles by a microfluidic approach: synthesis, in situ encapsulation and controlled release.

PubMed

Fang, Aiping; Cathala, Bernard

2011-01-01

This paper reports a microfluidic synthesis of biopolymer microparticles aiming at smart swelling. Monodisperse aqueous emulsion droplets comprising biopolymer and its cross-linking agent were formed in mineral oil and solidified in the winding microfluidic channels by in situ chaotic mixing, which resulted in internal chemical gelation for hydrogels. The achievement of pectin microparticles from in situ mixing pectin with its cross-linking agent, calcium ions, successfully demonstrates the reliability of this microfluidic synthesis approach. In order to achieve hydrogels with smart swelling, the following parameters and their impacts on the swelling behaviour, stability and morphology of microparticles were investigated: (1) the type of biopolymers (alginate or mixture of alginate and carboxymethylcellulose, A-CMC); (2) rapid mixing; (3) concentration and type of cross-linking agent. Superabsorbent microparticles were obtained from A-CMC mixture by using ferric chloride as an additional external cross-linking agent. The in situ encapsulation of a model protein, bovine serum albumin (BSA), was also carried out. As a potential protein drug-delivery system, the BSA release behaviours of the biopolymer particles were studied in simulated gastric and intestinal fluids. Compared with alginate and A-CMC microparticles cross-linked with calcium ions, A-CMC microparticles cross-linked with both calcium and ferric ions demonstrate a significantly delayed release. The controllable release profile, the facile encapsulation as well as their biocompatibility, biodegradability, mucoadhesiveness render this microfluidic approach promising in achieving biopolymer microparticles as protein drug carrier for site-specific release. Copyright © 2010 Elsevier B.V. All rights reserved.

Chitosan-Based Nano-Embedded Microparticles: Impact of Nanogel Composition on Physicochemical Properties

PubMed Central

Islam, Paromita; Water, Jorrit J.; Bohr, Adam; Rantanen, Jukka

2016-01-01

Chitosan-based nanogels have been widely applied as drug delivery vehicles. Spray-drying of said nanogels allows for the preparation of dry powder nano-embedded microparticles. In this work, chitosan-based nanogels composed of chitosan, alginate, and/or sodium tri-penta phosphate were investigated, particularly with respect to the impact of composition on the resulting physicochemical properties. Different compositions were obtained as nanogels with sizes ranging from 203 to 561 nm. The addition of alginate and exclusion of sodium tri-penta phosphate led to an increase in nanogel size. The nanogels were subsequently spray-dried to form nano-embedded microparticles with trehalose or mannitol as matrix excipient. The microparticles of different composition were mostly spherical with a smooth surface and a mass median aerodynamic diameter of 6–10 µm. Superior redispersibility was observed for microparticles containing amorphous trehalose. This study demonstrates the potential of nano-embedded microparticles for stabilization and delivery of nanogel-based delivery systems. PMID:28025505

Chitosan-Based Nano-Embedded Microparticles: Impact of Nanogel Composition on Physicochemical Properties.

PubMed

Islam, Paromita; Water, Jorrit J; Bohr, Adam; Rantanen, Jukka

2016-12-22

Chitosan-based nanogels have been widely applied as drug delivery vehicles. Spray-drying of said nanogels allows for the preparation of dry powder nano-embedded microparticles. In this work, chitosan-based nanogels composed of chitosan, alginate, and/or sodium tri-penta phosphate were investigated, particularly with respect to the impact of composition on the resulting physicochemical properties. Different compositions were obtained as nanogels with sizes ranging from 203 to 561 nm. The addition of alginate and exclusion of sodium tri-penta phosphate led to an increase in nanogel size. The nanogels were subsequently spray-dried to form nano-embedded microparticles with trehalose or mannitol as matrix excipient. The microparticles of different composition were mostly spherical with a smooth surface and a mass median aerodynamic diameter of 6-10 µm. Superior redispersibility was observed for microparticles containing amorphous trehalose. This study demonstrates the potential of nano-embedded microparticles for stabilization and delivery of nanogel-based delivery systems.

Methotrexate loaded alginate microparticles and effect of Ca2+ post-crosslinking: An in vitro physicochemical and biological evaluation.

PubMed

Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

2018-04-15

Methotrexate (MTX) loaded alginate microparticles were produced by simple water-in-oil (W/O) emulsion solvent diffusion method with homogenization and then subsequently cross-linked by Ca 2+ . The mean sizes of developed microparticles (bare non-crosslinked, crosslinked, drug-loaded non-crosslinked, and drug-loaded cross-linked) were found to be <11μm. The morphology of bare non-crosslinked and crosslinked microparticles were observed to be spherical with smooth surface morphology. However, MTX loaded non-crosslinked and crosslinked microparticles were found to have an irregular shape with rough surface morphology. The encapsulation efficiency (% EE) and loading capacity (% LC) of MTX loaded non-crosslinked microparticles were estimated to be 92.19±1.85 and 9.35±0.22, respectively. However, in case of cross-linked microparticles, the % EE and % LC values slightly decreased, i.e., 83.26±1.69% and 8.44±0.21%, respectively. Crosslinked microparticles were found to release MTX at a slower rate as compared to non-crosslinked microparticles. The physicochemical characterizations of microparticles by Fourier Transform Infrared Spectroscopy and High-Resolution X-Ray Diffraction have shown that drug encapsulated in the microparticles without chemical interactions has lost its crystalline nature. The biocompatibility and hemocompatibility studies of the microparticles have demonstrated that microparticles are biocompatible and were non-hemolytic at low concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Colon-specific delivery of 5-aminosalicylic acid from chitosan-Ca-alginate microparticles.

PubMed

Mladenovska, K; Raicki, R S; Janevik, E I; Ristoski, T; Pavlova, M J; Kavrakovski, Z; Dodov, M G; Goracinova, K

2007-09-05

Chitosan-Ca-alginate microparticles for colon-specific delivery and controlled release of 5-aminosalicylic acid after peroral administration were prepared using spray drying method followed by ionotropic gelation/polyelectrolyte complexation. Physicochemical characterization pointed to the negatively charged particles with spherical morphology having a mean diameter less than 9 microm. Chitosan was localized dominantly in the particle wall, while for alginate, a homogeneous distribution throughout the particles was observed. (1)H NMR, FTIR, X-ray and DSC studies indicated molecularly dispersed drug within the particles with preserved stability during microencapsulation and in simulated in vivo drug release conditions. In vitro drug release studies carried out in simulated in vivo conditions in respect to pH, enzymatic and salt content confirmed the potential of the particles to release the drug in a controlled manner. The diffusional exponents according to the general exponential release equation indicated anomalous (non-Fickian) transport in 5-ASA release controlled by a polymer relaxation, erosion and degradation. Biodistribution studies of [(131)I]-5-ASA loaded chitosan-Ca-alginate microparticles, carried out within 2 days after peroral administration to Wistar male rats in which TNBS colitis was induced, confirmed the dominant localization of 5-ASA in the colon with low systemic bioavailability.

Design and characterization of calcium alginate microparticles coated with polycations as protein delivery system.

PubMed

Zarate, J; Virdis, L; Orive, G; Igartua, M; Hernández, R M; Pedraz, J L

2011-01-01

Bovine serum albumin (BSA) loaded calcium alginate microparticles (MPs) produced in this study by a w/o emulsification and external gelation method exhibited spherical and fairly smooth and porous morphology with 1.052 ± 0.057 µm modal particle size. The high permeability of the calcium alginate hydrogel lead to a potent burst effect and too fast protein release. To overcome these problems, MPs were coated with polycations, such as chitosan, poly-L-lysine and DEAE-dextran. Our results demonstrated that coated MPs showed slower release and were able to significantly reduce the release of BSA in the first hour. Therefore, this method can be applied to prepare coated alginate MPs which could be an optimal system for the controlled release of biotherapeutic molecules. Nevertheless, further studies are needed to optimize delivery properties which could provide a sustained release of proteins.

Synthesis of Thermogelling Poly(N-isopropylacrylamide)-graft-chondroitin Sulfate Composites with Alginate Microparticles for Tissue Engineering

PubMed Central

Christiani, Thomas R.; Toomer, Katelynn; Sheehan, Joseph; Nitzl, Angelika; Branda, Amanda; England, Elizabeth; Graney, Pamela; Iftode, Cristina; Vernengo, Andrea J.

2016-01-01

Injectable biomaterials are defined as implantable materials that can be introduced into the body as a liquid and solidify in situ. Such materials offer the clinical advantages of being implanted minimally invasively and easily forming space-filling solids in irregularly shaped defects. Injectable biomaterials have been widely investigated as scaffolds for tissue engineering. However, for the repair of certain load-bearing areas in the body, such as the intervertebral disc, scaffolds should possess adhesive properties. This will minimize the risk of dislocation during motion and ensure intimate contact with the surrounding tissue, providing adequate transmission of forces. Here, we describe the preparation and characterization of a scaffold composed of thermally sensitive poly(N-isopropylacrylamide)-graft-chondroitin sulfate (PNIPAAM-g-CS) and alginate microparticles. The PNIPAAm-g-CS copolymer forms a viscous solution in water at RT, into which alginate particles are suspended to enhance adhesion. Above the lower critical solution temperature (LCST), around 30 °C, the copolymer forms a solid gel around the microparticles. We have adapted standard biomaterials characterization procedures to take into account the reversible phase transition of PNIPAAm-g-CS. Results indicate that the incorporation of 50 or 75 mg/ml alginate particles into 5% (w/v) PNIPAAm-g-CS solutions quadruple the adhesive tensile strength of PNIPAAm-gCS alone (p<0.05). The incorporation of alginate microparticles also significantly increases swelling capacity of PNIPAAm-g-CS (p<0.05), helping to maintain a space-filling gel within tissue defects. Finally, results of the in vitro toxicology assay kit, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and Live/Dead viability assay indicate that the adhesive is capable of supporting the survival and proliferation of encapsulated Human Embryonic Kidney (HEK) 293 cells over 5 days. PMID:27805604

Alginate/polymethacrylate copolymer microparticles for the intestinal delivery of enzymes.

PubMed

Scocca, Sarah; Faustini, Massimo; Villani, Simona; Munari, Eleonora; Conte, Ubaldo; Russo, Vincenzo; Riccardi, Alessia; Vigo, Daniele; Torre, Maria Luisa

2007-04-01

Proteins administered orally must pass through the gastric environment in order to reach their site of absorption in the intestine. How to protect these exogenously administered proteins from the damaging effects of gastric acid and pepsin proteolytic activity, which often induce irreversible structural and functional alterations to the molecules, is an intriguing challenge. Another problem is the physical and chemical instability of proteins during some technological processes, which often involve the use of organic solvents or high temperatures. In this study we investigated the use of alginate microparticles containing one of two enzymes, an enteric polymer and a lyoprotectant for the intestinal delivery of proteins. The two enzymes tested in this protein delivery system were lactate dehydrogenase and alpha-amylase: the former was chosen because of its sensitivity to denaturation, the latter for its relevance in nutrition and medicine. A sodium alginate aqueous solution containing the enteric polymer, a lyoprotectant and the enzyme was either extruded or sprayed into a calcium chloride solution, with the resultant formation of beads and microspheres which were freeze-dried. About 90% of the enzyme activity was maintained during the process of loading the proteins into the microparticles and the subsequent freeze-drying process. The stability of the encapsulated enzyme in an acid medium and the enzymatic activity in an intestinal environment were then investigated by a dissolution test. This consisted of exposing the microparticles to simulated gastric fluid (pH 1.2) for 2 hours and to simulated intestinal fluid (pH 7.5+/-0.1) for 1 hour. The morphology of the microparticles did not change in the acid environment, whereas they completely dissolved within 3 min in the simulated intestinal fluid. Residual enzymatic activity after the test remained satisfactory for both enzymes. In conclusion, these microparticle systems offer promise for applications in human and veterinary medicine as well as in human and animal nutrition.

Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

PubMed Central

Caetano, Liliana A.; Almeida, António J.; Gonçalves, Lídia M.D.

2016-01-01

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor.

PubMed

Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred; Micera, Silvestro

2009-04-01

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.

Mucoadhesive Microparticles for Gastroretentive Delivery: Preparation, Biodistribution and Targeting Evaluation

PubMed Central

Hou, Jing-Yi; Gao, Li-Na; Meng, Fan-Yun; Cui, Yuan-Lu

2014-01-01

The aim of this research was to prepare and characterize alginate-chitosan mucoadhesive microparticles containing puerarin. The microparticles were prepared by an emulsification-internal gelatin method using a combination of chitosan and Ca2+ as cationic components and alginate as anions. Surface morphology, particle size, drug loading, encapsulation efficiency and swelling ratio, in vitro drug released, in vitro evaluation of mucoadhesiveness and Fluorescence imaging of the gastrointestinal tract were determined. After optimization of the formulation, the encapsulation efficiency was dramatically increased from 70.3% to 99.2%, and a highly swelling ratio was achieved with a change in particle size from 50.3 ± 11.2 μm to 124.7 ± 25.6 μm. In ethanol induced gastric ulcers, administration of puerarin mucoadhesive microparticles at doses of 150 mg/kg, 300 mg/kg, 450 mg/kg and 600 mg/kg body weight prior to ethanol ingestion significantly protected the stomach ulceration. Consequently, significant changes were observed in inflammatory cytokines, such as prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and interleukin1β (IL-1β), in stomach tissues compared with the ethanol control group. In conclusion, core-shell type pH-sensitive mucoadhesive microparticles loaded with puerarin could enhance puerarin bioavailability and have the potential to alleviate ethanol-mediated gastric ulcers. PMID:25470180

Enzymatically cross-linked injectable alginate-g-pyrrole hydrogels for neovascularization.

PubMed

Devolder, Ross; Antoniadou, Eleni; Kong, Hyunjoon

2013-11-28

Microparticles capable of releasing protein drugs are often incorporated into injectable hydrogels to minimize their displacement at an implantation site, reduce initial drug burst, and further control drug release rates over a broader range. However, there is still a need to develop methods for releasing drug molecules over extended periods of time, in order to sustain the bioactivity of drug molecules at an implantation site. In this study, we hypothesized that a hydrogel formed through the cross-linking of pyrrole units linked to a hydrophilic polymer would release protein drugs in a more sustained manner, because of an enhanced association between cross-linked pyrrole groups and the drug molecules. To examine this hypothesis, we prepared hydrogels of alginate substituted with pyrrole groups, alginate-g-pyrrole, through a horse-radish peroxidase (HRP)-activated cross-linking of the pyrrole groups. The hydrogels were encapsulated with poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with vascular endothelial growth factor (VEGF). The resulting hydrogel system released VEGF in a more sustained manner than Ca(2+) alginate or Ca(2+) alginate-g-pyrrole gel systems. Finally, implantations of the VEGF-releasing HRP-activated alginate-g-pyrrole hydrogel system on chicken chorioallantoic membranes resulted in the formation of blood vessels in higher densities and with larger diameters, compared to other control conditions. Overall, the drug releasing system developed in this study will be broadly useful for regulating release rates of a wide array of protein drugs, and further enhance the quality of protein drug-based therapies. © 2013 Elsevier B.V. All rights reserved.

Multitarget sensing of glucose and cholesterol based on Janus hydrogel microparticles.

PubMed

Sun, Xiao-Ting; Zhang, Ying; Zheng, Dong-Hua; Yue, Shuai; Yang, Chun-Guang; Xu, Zhang-Run

2017-06-15

A visualized sensing method for glucose and cholesterol was developed based on the hemispheres of the same Janus hydrogel microparticles. Single-phase and Janus hydrogel microparticles were both generated using a centrifugal microfluidic chip. For glucose sensing, concanavalin A and fluorescein labeled dextran used for competitive binding assay were encapsulated in alginate microparticles, and the fluorescence of the microparticles was positively correlated with glucose concentration. For cholesterol sensing, the microparticles embedded with γ-Fe 2 O 3 nanoparticles were used as catalyst for the oxidation of 3,3',5,5'-Tetramethylbenzidine by H 2 O 2 , an enzymatic hydrolysis product of cholesterol. And the color transition was more sensitive in the microparticles than in solutions, indicating the microparticles are more applicable for visualized determination. Furthermore, Janus microparticles were employed for multitarget sensing in the two hemespheres, and glucose and cholesterol were detected within the same microparticles without obvious interference. Besides, the particles could be manipulated by an external magnetic field. The glucose and cholesterol levels were measured in human serum utilizing the microparticles, which confirmed the potential application of the microparticles in real sample detection. Copyright © 2017 Elsevier B.V. All rights reserved.

Microparticle-Mediated Delivery of BMP4 for Generation of Meiosis-Competent Germ Cells from Embryonic Stem Cells.

PubMed

Esfandiari, Fereshteh; Ashtiani, Mohammad Kazemi; Sharifi-Tabar, Mehdi; Saber, Maryam; Daemi, Hamed; Ghanian, Mohammad Hossein; Shahverdi, Abdolhossein; Baharvand, Hossein

2017-03-01

Producing meiosis-competent germ cells (GCs) from embryonic stem cells (ESCs) is essential for developing advanced therapies for infertility. Here, a novel approach is presented for generation of GCs from ESCs. In this regard, microparticles (MPs) have been developed from alginate sulfate loaded with bone morphogenetic protein 4 (BMP4). The results here show that BMP4 release from alginate sulfate MPs is significantly retarded by the sulfated groups compared to neat alginate. Then, BMP4-laden MPs are incorporated within the aggregates during differentiation of GCs from ESCs. It is observed that BMP4-laden MPs increase GC differentiation from ESCs at least twofold compared to the conventional soluble delivery method. Interestingly, following meiosis induction, Dazl, an intrinsic factor that enables GCs to enter meiosis, and two essential meiosis genes (Stra8 and Smc1b) are upregulated significantly in MP-induced aggregates compared to aggregates, which are formed by the conventional method. Together, these data show that controlled delivery of BMP4 during ESC differentiation into GC establish meiosis-competent GCs which can serve as an attractive GC source for reproductive medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel method for the production of core-shell microparticles by inverse gelation optimized with artificial intelligent tools.

PubMed

Rodríguez-Dorado, Rosalia; Landín, Mariana; Altai, Ayça; Russo, Paola; Aquino, Rita P; Del Gaudio, Pasquale

2018-03-01

Numerous studies have been focused on hydrophobic compounds encapsulation as oils. In fact, oils can provide numerous health benefits as synergic ingredient combined with other hydrophobic active ingredients. However, stable microparticles for pharmaceutical purposes are difficult to achieve when commonly techniques are used. In this work, sunflower oil was encapsulated in calcium-alginate capsules by prilling technique in co-axial configuration. Core-shell beads were produced by inverse gelation directly at the nozzle using a w/o emulsion containing aqueous calcium chloride solution in sunflower oil pumped through the inner nozzle while an aqueous alginate solution, coming out from the annular nozzle, produced the beads shell. To optimize process parameters artificial intelligence tools were proposed to optimize the numerous prilling process variables. Homogeneous and spherical microcapsules with narrow size distribution and a thin alginate shell were obtained when the parameters as w/o constituents, polymer concentrations, flow rates and frequency of vibration were optimized by two commercial software, FormRules® and INForm®, which implement neurofuzzy logic and Artificial Neural Networks together with genetic algorithms, respectively. This technique constitutes an innovative approach for hydrophobic compounds microencapsulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Photo-crosslinked alginate hydrogels support enhanced matrix accumulation by nucleus pulposus cells in vivo.

PubMed

Chou, A I; Akintoye, S O; Nicoll, S B

2009-10-01

Intervertebral disc (IVD) degeneration is a major health concern in the United States. Replacement of the nucleus pulposus (NP) with injectable biomaterials represents a potential treatment strategy for IVD degeneration. The objective of this study was to characterize the extracellular matrix (ECM) assembly and functional properties of NP cell-encapsulated, photo-crosslinked alginate hydrogels in comparison to ionically crosslinked alginate constructs. Methacrylated alginate was synthesized by esterification of hydroxyl groups with methacrylic anhydride. Bovine NP cells were encapsulated in alginate hydrogels by ionic crosslinking using CaCl(2) or through photo-crosslinking upon exposure to long-wave UV light in the presence of a photoinitiator. The hydrogels were evaluated in vitro by gross and histological analysis and in vivo using a murine subcutaneous pouch model. In vivo samples were analyzed for gene expression, ECM localization and accumulation, and equilibrium mechanical properties. Ionically crosslinked hydrogels exhibited inferior proteoglycan accumulation in vitro and were unable to maintain structural integrity in vivo. In further studies, photo-crosslinked alginate hydrogels were implanted for up to 8 weeks to examine NP tissue formation. Photo-crosslinked hydrogels displayed temporal increases in gene expression and assembly of type II collagen and proteoglycans. Additionally, hydrogels remained intact over the duration of the study and the equilibrium Young's modulus increased from 1.24+/-0.09 kPa to 4.31+/-1.39 kPa, indicating the formation of functional matrix with properties comparable to those of the native NP. These findings support the use of photo-crosslinked alginate hydrogels as biomaterial scaffolds for NP replacement.

A novel bio electro active alginate-aniline tetramer/ agarose scaffold for tissue engineering: synthesis, characterization, drug release and cell culture study.

PubMed

Atoufi, Zhale; Zarrintaj, Payam; Motlagh, Ghodratollah Hashemi; Amiri, Anahita; Bagher, Zohreh; Kamrava, Seyed Kamran

2017-10-01

In this study, synthesis of a novel biocompatible stimuli-responsive conducting hydrogel based on agarose/alginate-aniline tetramer with the capability of a tailored electrically controlled drug-release for neuroregeneration is investigated. First, aniline tetramer is synthesized and grafted onto sodium alginate. Then, this material is added to agarose as an electrical conductivity modifier to obtain Agarose/alginate-aniline tetramer hydrogel. The synthesized materials are characterized by H NMR and FTIR. The hydrogels are prepared with varying content of aniline tetramer and their swelling-deswelling and shape memory behavior is evaluated. The electroactivity and ionic conductivity of hydrogels against temperature is measured. The sample with 10% aniline tetramer (AT10) reveals the highest ionic conductivity. In MTT and SEM assays, AT10 shows the best cell viability and cell proliferation due to its highest ionic conductivity highlighting the fact that electrical stimuli cell signaling. Hydrogels also represent great potentials for passive and electro-stimulated dexamethasone release. These results demonstrate that the newly developed conducting hydrogels are promising materials for neuroregenerative medicine.

Matrix polyelectrolyte capsules based on polysaccharide/MnCO₃ hybrid microparticle templates.

PubMed

Wei, Qingrong; Ai, Hua; Gu, Zhongwei

2011-06-15

An efficient strategy for biomacromolecule encapsulation based on spontaneous deposition into polysaccharide matrix-containing capsules is introduced in this study. First, hybrid microparticles composed of manganese carbonate and ionic polysaccharides including sodium hyaluronate (HA), sodium alginate (SA) and dextran sulfate sodium (DS) with narrow size distribution were synthesized to provide monodisperse templates. Incorporation of polysaccharide into the hybrid templates was successful as verified by thermogravimetric analysis (TGA) and confocal laser scanning microscopy (CLSM). Matrix polyelectrolyte microcapsules were fabricated through layer-by-layer (LbL) self-assembly of oppositely charged polyelectrolytes (PEs) onto the hybrid particles, followed by removal of the inorganic part of the cores, leaving polysaccharide matrix inside the capsules. The loading and release properties of the matrix microcapsules were investigated using myoglobin as a model biomacromolecule. Compared to matrix-free capsules, the matrix capsules had a much higher loading capacity up to four times; the driving force is mostly due to electrostatic interactions between myoglobin and the polysaccharide matrix. From our observations, for the same kind of polysaccharide, a higher amount of polysaccharide inside the capsules usually led to better loading capacity. The release behavior of the loaded myoglobin could be readily controlled by altering the environmental pH. These matrix microcapsules may be used as efficient delivery systems for various charged water-soluble macromolecules with applications in biomedical fields. Copyright © 2010 Elsevier B.V. All rights reserved.

In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

PubMed

Zhang, J; Wang, Q; Wang, A

2010-02-01

In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

Bioactive Molecules Release and Cellular Responses of Alginate-Tricalcium Phosphate Particles Hybrid Gel

PubMed Central

Bang, Sumi; Zhang, Shengmin

2017-01-01

In this article, a hybrid gel has been developed using sodium alginate (Alg) and α-tricalcium phosphate (α-TCP) particles through ionic crosslinking process for the application in bone tissue engineering. The effects of pH and composition of the gel on osteoblast cells (MC3T3) response and bioactive molecules release have been evaluated. At first, a slurry of Alg and α-TCP has been prepared using an ultrasonicator for the homogeneous distribution of α-TCP particles in the Alg network and to achieve adequate interfacial interaction between them. After that, CaCl2 solution has been added to the slurry so that ionic crosslinked gel (Alg-α-TCP) is formed. The developed hybrid gel has been physico-chemically characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and a swelling study. The SEM analysis depicted the presence of α-TCP micro-particles on the surface of the hybrid gel, while cross-section images signified that the α-TCP particles are fully embedded in the porous gel network. Different % swelling ratio at pH 4, 7 and 7.4 confirmed the pH responsiveness of the Alg-α-TCP gel. The hybrid gel having lower % α-TCP particles showed higher % swelling at pH 7.4. The hybrid gel demonstrated a faster release rate of bovine serum albumin (BSA), tetracycline (TCN) and dimethyloxalylglycine (DMOG) at pH 7.4 and for the grade having lower % α-TCP particles. The MC3T3 cells are viable inside the hybrid gel, while the rate of cell proliferation is higher at pH 7.4 compared to pH 7. The in vitro cytotoxicity analysis using thiazolyl blue tetrazolium bromide (MTT), bromodeoxyuridine (BrdU) and neutral red assays ascertained that the hybrid gel is non-toxic for MC3T3 cells. The experimental results implied that the non-toxic and biocompatible Alg-α-TCP hybrid gel could be used as scaffold in bone tissue engineering. PMID:29135939

Ionic liquid as a potential solvent for preparation of collagen-alginate-hydroxyapatite beads as bone filler.

PubMed

Iqbal, Bushra; Sarfaraz, Zenab; Muhammad, Nawshad; Ahmad, Pervaiz; Iqbal, Jibran; Khan, Zia Ul Haq; Gonfa, Girma; Iqbal, Farasat; Jamal, Arshad; Rahim, Abdur

2018-07-01

In this study, collagen/alginate/hydroxyapatite beads having different proportions were prepared as bone fillers for the restoration of osteological defects. Ionic liquid was used to dissolve the collagen and subsequently the solution was mixed with sodium alginate solution. Hydroxyapatite was added in different proportions, with the rationale to enhance mechanical as well as biological properties. The prepared solutions were given characteristic bead shapes by dropwise addition into calcium chloride solution. The prepared beads were characterized using FTIR, XRD, TGA and SEM analysis. Microhardness testing was used to evaluate the mechanical properties. The prepared beads were investigated for water adsorption behavior to ascertain its ability for body fluid uptake and adjusted accordingly to the bone cavity. Drug loading and subsequently the antibacterial activity was investigated for the prepared beads. The biocompatibility was assessed using the hemolysis testing and cell proliferation assay. The prepared collagen-alginate-HA beads, having biocompatibility and good mechanical properties, have showed an option of promising biologically active bone fillers for bone regeneration.

Wheat germ agglutinin-conjugated chitosan-Ca-alginate microparticles for local colon delivery of 5-FU: development and in vitro characterization.

PubMed

Glavas Dodov, M; Calis, S; Crcarevska, M S; Geskovski, N; Petrovska, V; Goracinova, K

2009-11-03

The aim of this work was to prepare lectin-conjugated chitosan-Ca-alginate microparticles (MPs) loaded with acid-resistant particles of 5-fluorouracil (5-FU) for efficient local treatment of colon cancer. MPs were prepared by a novel one-step spray-drying technique and after wheat germ agglutinin (WGA) conjugation, they were characterized for size, swelling behavior, surface charge, entrapment efficiency and in vitro drug release. Prepared particles were spherical, with 6.73 microg/mg of WGA conjugated onto their surface. The size and zeta potential increased after conjugation, from 6.6 to 14.7 microm and from 9.6 to 15.3 mV, while drug encapsulation was 75.6 and 72.8%, respectively after conjugation. The swelling behavior of beads was mainly determined by properties of the cross-linked chitosan-alginate network. In vitro drug release studies carried out in simulated in vivo conditions with respect to pH, confirmed the potential of the particles to release the drug in a controlled manner. Also, the drug release was not significantly affected by WGA conjugation. The retention of biorecognitive activity of WGA after covalent coupling to MPs was confirmed by haemagglutination test. Functionalized MPs showed excessive mucoadhesiveness in vitro, due to the positive surface charge, pH-dependent swelling of the matrix and lectin-sugar recognition.

Studies of ciprofloxacin encapsulation on alginate/pectin matrixes and its relationship with biodisponibility.

PubMed

Islan, Germán A; de Verti, Ignacio Pérez; Marchetti, Sergio G; Castro, Guillermo R

2012-07-01

Screening of ciprofloxacin (Cip) with selected biopolymers brings about 90% antibiotic interactions with a coacervate composed of alginate/high metoxylated pectin in 2:1 ratio. Fourier transform infrared spectroscopy analysis provides information about the nature of this interaction, revealing ionic and hydrophobic patterns among the molecules. Alginate/high methoxylated pectin gel microspheres developed by ionic gelation encapsulates 46.8 ± 5.0% Cip. The gel matrix can release Cip in a sustained manner, releasing 42.7 ± 0.2% in 2 h under simulated stomach pH conditions, and 83.3 ± 1.1% Cip release in 80 mM phosphate at pH = 7.40 (intestinal). The increase of sodium chloride from 50 to 200 mM implies a Cip release from 69.0 ± 1.5% to 95.1 ± 3.6% respectively in 2 h. Scanning electron microscopy revealed the cohesive effect of HM pectin over alginate molecules on the microsphere surface. Those results guarantee all Cip contained in the alginate/HM pectin microspheres could be released in an established kinetic profile along the gastrointestinal tract, avoiding the Cip undesirable side effects during absorption.

Development of collagen-hydroxyapatite scaffolds incorporating PLGA and alginate microparticles for the controlled delivery of rhBMP-2 for bone tissue engineering.

PubMed

Quinlan, Elaine; López-Noriega, Adolfo; Thompson, Emmet; Kelly, Helena M; Cryan, Sally Ann; O'Brien, Fergal J

2015-01-28

The spatiotemporally controlled delivery of the pro-osteogenic factor rhBMP-2 would overcome most of the severe secondary effects linked to the products delivering this protein for bone regeneration. With this in mind, the aim of the present work was to develop a controlled rhBMP-2 release system using collagen-hydroxyapatite (CHA) scaffolds, which had been previously optimized for bone regeneration, as delivery platforms to produce a device with enhanced capacity for bone repair. Spray-drying and emulsion techniques were used to encapsulate bioactive rhBMP-2 in alginate and PLGA microparticles, with a high encapsulation efficiency. After incorporation of these microparticles into the scaffolds, rhBMP-2 was delivered in a sustained fashion for up to 28days. When tested in vitro with osteoblasts, these eluting materials showed an enhanced pro-osteogenic effect. From these results, an optimal rhBMP-2 eluting scaffold composition was selected and implanted in critical-sized calvarial defects in a rat model, where it demonstrated an excellent healing capacity in vivo. These platforms have an immense potential in the field of tissue regeneration; by tuning the specific therapeutic molecule to the tissue of interest and by utilizing different collagen-based scaffolds, similar systems can be developed for enhancing the healing of a diverse range of tissues and organs. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Environmental Stresses and in Vitro Digestion on the Release of Tocotrienols Encapsulated Within Chitosan-Alginate Microcapsules.

PubMed

Tan, Phui Yee; Tan, Tai Boon; Chang, Hon Weng; Tey, Beng Ti; Chan, Eng Seng; Lai, Oi Ming; Sham Baharin, Badlishah; Nehdi, Imededdine Arbi; Tan, Chin Ping

2017-12-06

Considering the health benefits of tocotrienols, continuous works have been done on the encapsulation and delivery of these compounds. In this study, we encapsulated tocotrienols in chitosan-alginate microcapsules and evaluated their release profile. Generally, these tocotrienols microcapsules (TM) displayed high thermal stability. When subjected to pH adjustments (pH 1-9), we observed that the release of tocotrienols was the highest (33.78 ± 0.18%) under basic conditions. The TM were also unstable against the effect of ionic strength, with a high release (70.73 ± 0.04%) of tocotrienols even at a low sodium chloride concentration (50 mM). As for the individual isomers, δ-tocotrienol was the most sensitive to pH and ionic strength. In contrast, β-/γ-tocotrienols were the most ionic-stable isomers but more responsive toward thermal treatment. Simulated gastrointestinal model showed that the chitosan-alginate-based TM could be used to retain tocotrienols in the gastric and subsequently release them in the intestines for possible absorption.

Bio-based barium alginate film: Preparation, flame retardancy and thermal degradation behavior.

PubMed

Liu, Yun; Zhang, Chuan-Jie; Zhao, Jin-Chao; Guo, Yi; Zhu, Ping; Wang, De-Yi

2016-03-30

A bio-based barium alginate film was prepared via a facile ionic exchange and casting approach. Its flammability, thermal degradation and pyrolysis behaviors, thermal degradation mechanism were studied systemically by limiting oxygen index (LOI), vertical burning (UL-94), microscale combustion calorimetry (MCC), thermogravimetric analysis (TGA) coupled with Fourier transform infrared analysis (FTIR) and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). It showed that barium alginate film had much higher LOI value (52.0%) than that of sodium alginate film (24.5%). Moreover, barium alginate film passed the UL-94 V-0 rating, while the sodium alginate film showed no classification. Importantly, peak of heat release rate (PHRR) of barium alginate film in MCC test was much lower than that of sodium alginate film, suggested that introduction of barium ion into alginate film significantly decreased release of combustible gases. TG-FTIR and Py-GC-MS results indicated that barium alginate produced much less flammable products than that of sodium alginate in whole thermal degradation procedure. Finally, a possible degradation mechanism of barium alginate had been proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model.

PubMed

Back, Ja Hoon; Cho, Wan Jin; Kim, Jun Ho; Park, Il Kyu; Kwon, Sung Won

2016-04-01

Postsurgical adhesion formation is a concern in every field of surgery. We evaluated the efficacy of hyaluronic acid/sodium alginate-based microparticle anti-adhesive agents (MP) for the prevention of postsurgical adhesion formation in a standardized rabbit model. To evaluate the anti-adhesion effect, a uterus-abdominal wall abrasion model was created in rabbits. On the surface of the injured uterus, an anti-adhesive agent, Interceed(®) or MP, was applied (positive control and study groups, respectively; n = 10 each). In another group of 10 animals, neither agent was applied (negative control group). The adhesion levels were graded 3 weeks after surgery. Acute and chronic toxicity was also evaluated. The grade of adhesion was significantly lower in the MP group than in the negative control and positive control groups. No evidence of acute or chronic toxicity induced by this material was found in blood and tissue analysis. MP shows potential as an effective novel type of resorbable biomaterial to reduce postoperative adhesion. The easy placement and handling of this material make the MP powder attractive as a tissue adhesion barrier.

Formulation Development, Process Optimization, and In Vitro Characterization of Spray-Dried Lansoprazole Enteric Microparticles

PubMed Central

Vora, Chintan; Patadia, Riddhish; Mittal, Karan; Mashru, Rajashree

2016-01-01

This research focuses on the development of enteric microparticles of lansoprazole in a single step by employing the spray drying technique and studies the effects of variegated formulation/process variables on entrapment efficiency and in vitro gastric resistance. Preliminary trials were undertaken to optimize the type of Eudragit and its various levels. Further trials included the incorporation of plasticizer triethyl citrate and combinations of other polymers with Eudragit S 100. Finally, various process parameters were varied to investigate their effects on microparticle properties. The results revealed Eudragit S 100 as the paramount polymer giving the highest gastric resistance in comparison to Eudragit L 100-55 and L 100 due to its higher pH threshold and its polymeric backbone. Incorporation of plasticizer not only influenced entrapment efficiency, but diminished gastric resistance severely. On the contrary, polymeric combinations reduced entrapment efficiency for both sodium alginate and glyceryl behenate, but significantly influenced gastric resistance for only sodium alginate and not for glyceryl behenate. The optimized process parameters were comprised of an inlet temperature of 150°C, atomizing air pressure of 2 kg/cm2, feed solution concentration of 6% w/w, feed solution spray rate of 3 ml/min, and aspirator volume of 90%. The SEM analysis revealed smooth and spherical shape morphologies. The DSC and PXRD study divulged the amorphous nature of the drug. Regarding stability, the product was found to be stable under 3 months of accelerated and long-term stability conditions as per ICH Q1A(R2) guidelines. Thus, the technique offers a simple means to generate polymeric enteric microparticles that are ready to formulate and can be directly filled into hard gelatin capsules. PMID:27222612

Fabrication of patterned calcium cross-linked alginate hydrogel films and coatings through reductive cation exchange.

PubMed

Bruchet, Marion; Melman, Artem

2015-10-20

Calcium cross-linked alginate hydrogels are widely used in targeted drug delivery, tissue engineering, wound treatment, and other biomedical applications. We developed a method for preparing homogeneous alginate hydrogels cross-linked with Ca(2+) cations using reductive cation exchange in homogeneous iron(III) cross-linked alginate hydrogels. Treatment of iron(III) cross-linked alginate hydrogels with calcium salts and sodium ascorbate results in reduction of iron(III) cations to iron(II) that are instantaneously replaced with Ca(2+) cations, producing homogeneous ionically cross-linking hydrogels. Alternatively, the cation exchange can be performed by photochemical reduction in the presence of calcium chloride using a sacrificial photoreductant. This approach allows fabrication of patterned calcium alginate hydrogels through photochemical patterning of iron(III) cross-linked alginate hydrogel followed by the photochemical reductive exchange of iron cations to calcium. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling the controllable pH-responsive swelling and pore size of networked alginate based biomaterials.

PubMed

Chan, Ariel W; Neufeld, Ronald J

2009-10-01

Semisynthetic network alginate polymer (SNAP), synthesized by acetalization of linear alginate with di-aldehyde, is a pH-responsive tetrafunctionally linked 3D gel network, and has potential application in oral delivery of protein therapeutics and active biologicals, and as tissue bioscaffold for regenerative medicine. A constitutive polyelectrolyte gel model based on non-Gaussian polymer elasticity, Flory-Huggins liquid lattice theory, and non-ideal Donnan membrane equilibria was derived, to describe SNAP gel swelling in dilute and ionic solutions containing uni-univalent, uni-bivalent, bi-univalent or bi-bi-valent electrolyte solutions. Flory-Huggins interaction parameters as a function of ionic strength and characteristic ratio of alginates of various molecular weights were determined experimentally to numerically predict SNAP hydrogel swelling. SNAP hydrogel swells pronouncedly to 1000 times in dilute solution, compared to its compact polymer volume, while behaving as a neutral polymer with limited swelling in high ionic strength or low pH solutions. The derived model accurately describes the pH-responsive swelling of SNAP hydrogel in acid and alkaline solutions of wide range of ionic strength. The pore sizes of the synthesized SNAP hydrogels of various crosslink densities were estimated from the derived model to be in the range of 30-450 nm which were comparable to that measured by thermoporometry, and diffusion of bovine serum albumin. The derived equilibrium swelling model can characterize hydrogel structure such as molecular weight between crosslinks and crosslinking density, or can be used as predictive model for swelling, pore size and mechanical properties if gel structural information is known, and can potentially be applied to other point-link network polyelectrolytes such as hyaluronic acid gel.

Effect on Ammonium Bromide in dielectric behavior based Alginate Solid Biopolymer electrolytes

NASA Astrophysics Data System (ADS)

Fuzlin, A. F.; Rasali, N. M. J.; Samsudin, A. S.

2018-04-01

This paper present the development of solid biopolymer electrolytes (SBEs) system which has been accomplished by incorporating various composition of ionic dopant namely ammonium bromide (NH4Br) with alginate solution casting method. The prepared sample of SBEs has been analyzed via electrical impedance spectroscopy (EIS) showed that the ionic conductivity at room temperature was increased from 4.67 x 10-7 S cm-1 for un-doped sample to optimum value at 4.41 x 10-5 S cm-1 for composition of 20 wt. % NH4Br. The SBEs system was found to obey the Arrhenius characteristics with R2~1where all sample is thermally activated when increasing temperature. The dielectric behavior of the alginate-NH4Br SBEs system were measured using complex permittivity (ε*) and complex electrical modulus (M*) and shown the non-debye behavior where no single relaxation was found for present SBEs system.

Ionic liquids for nano- and microstructures preparation. Part 2: Application in synthesis.

PubMed

Łuczak, Justyna; Paszkiewicz, Marta; Krukowska, Anna; Malankowska, Anna; Zaleska-Medynska, Adriana

2016-01-01

Ionic liquids (ILs) are widely applied to prepare metal nanoparticles and 3D semiconductor microparticles. Generally, they serve as a structuring agent or reaction medium (solvent), however it was also demonstrated that ILs can play a role of a co-solvent, metal precursor, reducing as well as surface modifying agent. The crucial role and possible types of interactions between ILs and growing particles have been presented in the Part 1 of this review paper. Part 2 of the paper gives a comprehensive overview of recent experimental studies dealing with application of ionic liquids for preparation of metal and semiconductor based nano- and microparticles. A wide spectrum of preparation routes using ionic liquids is presented, including precipitation, sol-gel technique, hydrothermal method, nanocasting and ray-mediated methods (microwave, ultrasound, UV-radiation and γ-radiation). It was found that ionic liquids formed of a 1-butyl-3-methylimidazolium [BMIM] combined with tetrafluoroborate [BF4], hexafluorophosphate [PF6], and bis(trifluoromethanesulfonyl)imide [Tf2N] are the most often used ILs in the synthesis of nano- and microparticles, due to their low melting temperature, low viscosity and good transportation properties. Nevertheless, examples of other IL classes with intrinsic nanoparticles stabilizing abilities such as phosphonium and ammonium derivatives are also presented. Experimental data revealed that structure of ILs (both anion and cation type) affects the size and shape of formed metal particles, and in some cases may even determine possibility of particles formation. The nature of the metal precursor determines its affinity to polar or nonpolar domains of ionic liquid, and therefore, the size of the nanoparticles depends on the size of these regions. Ability of ionic liquids to form varied extended interactions with particle precursor as well as other compounds presented in the reaction media (water, organic solvents etc.) provides nano- and microstructures with different morphologies (0D nanoparticles, 1D nanowires, rods, 2D layers, sheets, and 3D features of molecules). ILs interact efficiently with microwave irradiation, thus even small amount of IL can be employed to increase the dielectric constant of nonpolar solvents used in the synthesis. Thus, combining the advantages of ionic liquids and ray-mediated methods resulted in the development of new ionic liquid-assisted synthesis routes. One of the recently proposed approaches of semiconductor particles preparation is based on the adsorption of semiconductor precursor molecules at the surface of micelles built of ionic liquid molecules playing a role of a soft template for growing microparticles. Copyright © 2015 Elsevier B.V. All rights reserved.

In-situ photopolymerization of monodisperse and discoid oxidized methacrylated alginate microgels in a microfluidic channel

DOE PAGES

Wang, Shuo; Jeon, Oju; Shankles, Peter G.; ...

2016-02-03

Here, we present a simple microfluidic technique to in-situ photopolymerize (by 365 nm ultraviolet) monodisperse oxidized methacrylated alginate (OMA) microgels using a photoinitiator (VA-086). By this technique, we generated monodisperse spherical OMA beads and discoid non-spherical beads with better shape consistency than ionic crosslinking methods do. We found that a high monomer concentration (8 w/v %), a high photoinitiator concentration (1.5 w/v %) and absence of oxygen are critical factors to cure OMA microgels. This photopolymerizing method is an alternative to current methods to form alginate microgels and is a simpler approach to generate non-spherical alginate microgels.

Alginate Particles as Platform for Drug Delivery by the Oral Route: State-of-the-Art.

PubMed

Sosnik, Alejandro

2014-01-01

Pharmaceutical research and development aims to design products with ensured safety, quality, and efficacy to treat disease. To make the process more rational, coherent, efficient, and cost-effective, the field of Pharmaceutical Materials Science has emerged as the systematic study of the physicochemical properties and behavior of materials of pharmaceutical interest in relation to product performance. The oral route is the most patient preferred for drug administration. The presence of a mucus layer that covers the entire gastrointestinal tract has been exploited to expand the use of the oral route by developing a mucoadhesive drug delivery system that showed a prolonged residence time. Alginic acid and sodium and potassium alginates have emerged as one of the most extensively explored mucoadhesive biomaterials owing to very good cytocompatibility and biocompatibility, biodegradation, sol-gel transition properties, and chemical versatility that make possible further modifications to tailor their properties. The present review overviews the most relevant applications of alginate microparticles and nanoparticles for drug administration by the oral route and discusses the perspectives of this biomaterial in the future.

An Alginate/Cyclodextrin Spray Drying Matrix to Improve Shelf Life and Antioxidant Efficiency of a Blood Orange By-Product Extract Rich in Polyphenols: MMPs Inhibition and Antiglycation Activity in Dysmetabolic Diseases.

PubMed

Lauro, Maria Rosaria; Crascì, Lucia; Giannone, Virgilio; Ballistreri, Gabriele; Fabroni, Simona; Sansone, Francesca; Rapisarda, Paolo; Panico, Anna Maria; Puglisi, Giovanni

2017-01-01

Alginate and β -cyclodextrin were used to produce easily dosable and spray-dried microsystems of a dried blood orange extract with antidysmetabolic properties, obtained from a by-product fluid extract. The spray-dried applied conditions were able to obtain a concentrate dried extract without the loss of AOA and with TPC and TMA values of 35-40% higher than that of the starting material. They were also effective in producing microparticles with 80-100% of encapsulation efficiency. The 2% sodium alginate was capable of improving the extract shelf life , while the beta-cyclodextrin (1 : 1 molar ratio with dried extract) prolonged the extract antioxidant efficiency by 6 hours. The good inhibition effect of the dried extract on the AGE formation and the MMP-2 and MMP-9 activity is presumably due to a synergic effect exerted by both anthocyanin and bioflavonoid extract compounds and was improved by the use of alginate and cyclodextrin.

An Alginate/Cyclodextrin Spray Drying Matrix to Improve Shelf Life and Antioxidant Efficiency of a Blood Orange By-Product Extract Rich in Polyphenols: MMPs Inhibition and Antiglycation Activity in Dysmetabolic Diseases

PubMed Central

Giannone, Virgilio; Ballistreri, Gabriele; Fabroni, Simona; Rapisarda, Paolo; Panico, Anna Maria; Puglisi, Giovanni

2017-01-01

Alginate and β-cyclodextrin were used to produce easily dosable and spray-dried microsystems of a dried blood orange extract with antidysmetabolic properties, obtained from a by-product fluid extract. The spray-dried applied conditions were able to obtain a concentrate dried extract without the loss of AOA and with TPC and TMA values of 35–40% higher than that of the starting material. They were also effective in producing microparticles with 80–100% of encapsulation efficiency. The 2% sodium alginate was capable of improving the extract shelf life, while the beta-cyclodextrin (1 : 1 molar ratio with dried extract) prolonged the extract antioxidant efficiency by 6 hours. The good inhibition effect of the dried extract on the AGE formation and the MMP-2 and MMP-9 activity is presumably due to a synergic effect exerted by both anthocyanin and bioflavonoid extract compounds and was improved by the use of alginate and cyclodextrin. PMID:29230268

The role of alginate in Pseudomonas aeruginosa EPS adherence, viscoelastic properties and cell attachment.

PubMed

Orgad, Oded; Oren, Yoram; Walker, Sharon L; Herzberg, Moshe

2011-08-01

Among various functions, extracellular polymeric substances (EPS) provide microbial biofilms with mechanical stability and affect initial cell attachment, the first stage in the biofilm formation process. The role of alginate, an abundant polysaccharide in Pseudomonas aeruginosa biofilms, in the viscoelastic properties and adhesion kinetics of EPS was analyzed using a quartz crystal microbalance with dissipation (QCM-D) monitoring technology. EPS was extracted from two P. aeruginosa biofilms, a wild type strain, PAO1, and a mucoid strain, PAOmucA22 that over-expresses alginate production. The higher alginate content in the EPS originating from the mucoid biofilms was clearly shown to increase both the rate and the extent of attachment of the EPS, as well as the layer's thickness. Also, the presence of calcium and elevated ionic strength increased the thickness of the EPS layer. Dynamic light scattering (DLS) showed that the presence of calcium and elevated ionic strength induced intermolecular attractive interactions in the mucoid EPS molecules. For the wild type EPS, in the presence of calcium, an elevated shift in the distribution of the diffusion coefficients was observed with DLS due to a more compacted conformation of the EPS molecules. Moreover, the alginate over-expression effect on EPS adherence was compared to the effect of alginate over-expression on P. aeruginosa cell attachment. In a parallel plate flow cell, under similar hydraulic and aquatic conditions as those applied for the EPS adsorption tests in the QCM-D flow cell, reduced adherence of the mucoid strain was clearly observed compared to the wild type isogenic bacteria. The results suggest that alginate contributes to steric hindrance and shielding of cell surface features and adhesins that are known to promote cell attachment. © 2011 Taylor & Francis

Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

PubMed

Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

2014-02-01

The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

Novel Model-Based Inquiry of Ionic Bonding in Alginate Hydrogels Used in Tissue Engineering for High School Students

ERIC Educational Resources Information Center

Bowles, Robby D.; Saroka, James M.; Archer, Shivaun D.; Bonassar, Lawrence J.

2012-01-01

Because of cost and time, it is difficult to relate to students how fundamental chemical principles are involved in cutting edge biomedical breakthroughs being reported in the national media. The laboratory exercise presented here is aimed at high school chemistry students and uses alginate hydrogels, a common material used in tissue engineering,…

3D Cell Culture in Alginate Hydrogels

PubMed Central

Andersen, Therese; Auk-Emblem, Pia; Dornish, Michael

2015-01-01

This review compiles information regarding the use of alginate, and in particular alginate hydrogels, in culturing cells in 3D. Knowledge of alginate chemical structure and functionality are shown to be important parameters in design of alginate-based matrices for cell culture. Gel elasticity as well as hydrogel stability can be impacted by the type of alginate used, its concentration, the choice of gelation technique (ionic or covalent), and divalent cation chosen as the gel inducing ion. The use of peptide-coupled alginate can control cell–matrix interactions. Gelation of alginate with concomitant immobilization of cells can take various forms. Droplets or beads have been utilized since the 1980s for immobilizing cells. Newer matrices such as macroporous scaffolds are now entering the 3D cell culture product market. Finally, delayed gelling, injectable, alginate systems show utility in the translation of in vitro cell culture to in vivo tissue engineering applications. Alginate has a history and a future in 3D cell culture. Historically, cells were encapsulated in alginate droplets cross-linked with calcium for the development of artificial organs. Now, several commercial products based on alginate are being used as 3D cell culture systems that also demonstrate the possibility of replacing or regenerating tissue. PMID:27600217

Non-invasive endotracheal delivery of paclitaxel-loaded alginate microparticles.

PubMed

Alipour, Shohreh; Montaseri, Hashem; Khalili, Azadeh; Tafaghodi, Mohsen

2016-10-01

Aerosolized chemotherapeutics leads to higher, localized and continuous concentrations of active agents in lung tissue with lower side effects for other organs. The present study was performed on jugular vein cannulated rats which endothracheally received 4 mg/kg of free paclitaxel powder (Free-PTX), paclitaxel-loaded alginate microparticles (PTX-ALG-MPs) and i.v. paclitaxel (Anzatax(®)). Pharmacokinetic parameters for Free-PTX and PTX-ALG-MPs contain higher AUC, mean residence time (MRT),half-life and bioavailability, with lower elimination constant (ke). Statistical analysis showed that the amount of paclitaxel per gram of lung tissue after 0.5, 6 and 24 h after administration of Free-PTX was lower than PTX-ALG-MPs. Lung tissue AUC for Free-PTX was lower than PTX-ALG-MPs. According to the obvious advantages obtained, such as dose lowering and increasing paclitaxel residence time and half-life. It should be noted that cell cytotoxicity test on normal airway cell lines was not examined in this study but due to previous reports on safety of inhaled paclitaxel, it can be suggested that pulmonary delivery of paclitaxel can be a useful non-invasive route of administration compared with i.v administration.

Production of microparticles of molinate degrading biocatalysts using the spray drying technique.

PubMed

Lopes, Ana R; Sousa, Vera M; Estevinho, Berta N; Leite, José P; Moreira, Nuno F F; Gales, Luís; Rocha, Fernando; Nunes, Olga C

2016-10-01

Previous studies demonstrated the capability of mixed culture DC1 to mineralize the thiocarbamate herbicide molinate through the activity of molinate hydrolase (MolA). Because liquid suspensions are not compatible with long-term storage and are not easy to handle when bioremediation strategies are envisaged, in this study spray drying was evaluated as a cost-effective method to store and transport these molinate biocatalysts. Microparticles of mixed culture DC1 (DC1) and of cell free crude extracts containing MolA (MA) were obtained without any carrier polymer, and with calcium alginate (CA) or modified chitosan (MCt) as immobilizing agents. All the DC1 microparticles showed high molinate degrading activity upon storage for 6 months, or after 9 additions of ∼0.4 mM molinate over 1 month. The DC1-MCt microparticles were those with the highest survival rate and lowest heterogeneity. For MA microparticles, only MA-MCt degraded molinate. However, its Vmax was only 1.4% of that of the fresh cell free extract (non spray dried). The feasibility of using the DC1-MCt and MA-MCt microparticles in bioaugmentation processes was assessed in river water microcosms, using mass (g):volume (L) ratios of 1:13 and 1:0.25, respectively. Both type of microparticles removed ∼65-75% of the initial 1.5 mg L(-1) molinate, after 7 days of incubation. However, only DC1-MCt microparticles were able to degrade this environmental concentration of molinate without disturbing the native bacterial community. These results suggest that spray drying can be successfully used to produce DC1-MCt microparticles to remediate molinate polluted sites through a bioaugmentation strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanocomplexes of an insulinotropic drug: optimization, microparticle formation, and antidiabetic activity in rats

PubMed Central

Elmowafy, Enas; Osman, Rihab; El-Shamy, Abdel Hameed; Awad, Gehanne AS

2014-01-01

The aim of the present work was to test the ability of two non-diabetogenic carbohydrates to intranasally deliver the insulinotropic drug repaglinide (REP) for controlling blood glucose level. REP was loaded onto chitosan/alginate nanocomplexes (NCs) suitable for mucosal delivery and uptake. Improved stability and delivery characteristics were obtained by spray drying the selected NCs, yielding microparticles. A statistical experimental design was adopted to investigate the effects of the formulations’ variables on two critical responses: NC size and drug entrapment efficiency. Physicochemical characterizations of the network’s structures were done, and in vitro cytotoxicity and histopathological studies were conducted. The potential of the developed system to prolong the drug effect was tested on diabetic rats. The results showed that to attain particles suitable for nasal delivery, alginate should be used at its lowest level used in this study (0.6 mg/mL). A low level of chitosan (0.5 mg/mL) was needed when the drug was cation-loaded, while the high chitosan level (1 mg/mL) was more suitable when REP was anion-loaded. The best entrapment efficiency was achieved at a theoretical drug loading of 0.025 mg/mL. Discrete NCs could be rapidly recovered from the spray-dried microparticles. The cytotoxicity and histopathological studies indicated that such formulations were well tolerated. The antihyperglycemic activity of the nasally administered formulae was gradual but was significantly sustained over 24 hours, suggesting NC mucosal uptake. Nasal delivery of such dry powders achieved better glycemic control compared with the conventional oral tablets. PMID:25258534

Oral DNA vaccines based on CS-TPP nanoparticles and alginate microparticles confer high protection against infectious pancreatic necrosis virus (IPNV) infection in trout.

PubMed

Ahmadivand, Sohrab; Soltani, Mehdi; Behdani, Mahdi; Evensen, Øystein; Alirahimi, Ehsan; Hassanzadeh, Reza; Soltani, Ellahe

2017-09-01

Infectious pancreatic necrosis virus (IPNV) is the etiological agent of a contagious viral disease causing remarkable mortalities in different fish species. Despite the availability of commercial vaccines against IPN, the disease still constitutes one of the main threats to the aquaculture industry worldwide. In this study, we developed a DNA vaccine encoding the VP2 gene of IPNV and evaluated its ability to induce protective immunity in rainbow trout fry (3 g) at doses of 10 and 25 μg/fish and boosting with the same doses two weeks later through the oral route using chitosan/tripolyphosphate (CS-TPP) nanoparticles and alginate microparticles incorporated into fish feed. The distribution of the administered vaccines in different organs and transcription of VP2 gene were confirmed by RT-PCR assay at day 30 post boost-vaccination. Transcript levels of IFN-1, Mx-1, IgM, IgT and CD4 genes was dependent on vaccine dose and was significantly up-regulated in head kidney of all orally vaccinated fish groups compared to controls (pcDNA3.1). Cumulative mortalities post-challenge with virulent isolate of the virus were lower in the vaccinated fish and a relative percentage survival (RPS) of 59% and 82% were obtained for the 10 and 25 μg/fish pcDNA3.1-VP2 groups, respectively. Vaccination with the same amount of pcDNA3.1-VP2 encapsulated with CS-TPP nanoparticles resulted in RPS of 47 %and 70%, respectively. Detectable anti-IPNV antibodies were shown until 90 days postvaccination. The orally administrated vaccines significantly decreased VP4 transcripts thus contributing to reducing viral load in surviving fish on day 45 post-challenge. In conclusion, these results show good to high protection post-vaccination alongside with significant up-regulation of key immune genes and detectable levels of circulating antibodies after oral administration of the DNA vaccine formulated in CS-TPP nanoparticles and alginate microparticles in fish feed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent progress in biopolymer nanoparticle and microparticle formation by heat-treating electrostatic protein-polysaccharide complexes.

PubMed

Jones, Owen G; McClements, David Julian

2011-09-14

Functional biopolymer nanoparticles or microparticles can be formed by heat treatment of globular protein-ionic polysaccharide electrostatic complexes under appropriate solution conditions. These biopolymer particles can be used as encapsulation and delivery systems, fat mimetics, lightening agents, or texture modifiers. This review highlights recent progress in the design and fabrication of biopolymer particles based on heating globular protein-ionic polysaccharide complexes above the thermal denaturation temperature of the proteins. The influence of biopolymer type, protein-polysaccharide ratio, pH, ionic strength, and thermal history on the characteristics of the biopolymer particles formed is reviewed. Our current understanding of the underlying physicochemical mechanisms of particle formation and properties is given. The information provided in this review should facilitate the rational design of biopolymer particles with specific physicochemical and functional attributes, as well as stimulate further research in identifying the physicochemical origin of particle formation. Copyright © 2010 Elsevier B.V. All rights reserved.

Role of alginate in antibacterial finishing of textiles.

PubMed

Li, Jiwei; He, Jinmei; Huang, Yudong

2017-01-01

Antibacterial finishing of textiles has been introduced as a necessary process for various purposes especially creating a fabric with antimicrobial activities. Currently, the textile industry continues to look for textiles antimicrobial finishing process based on sustainable biopolymers from the viewpoints of environmental friendliness, industrialization, and economic concerns. This paper reviews the role of alginate, a sustainable biopolymer, in the development of antimicrobial textiles, including both basic physicochemical properties of alginate such as preparation, chemical structure, molecular weight, solubility, viscosity, and sol-gel transformation property. Then different processing routes (e.g. nanocomposite coating, ionic cross-linking coating, and Layer-by-Layer coating) for the antibacterial finishing of textiles by using alginate are revised in some detail. The achievements in this area have increased our knowledge of alginate application in the field of textile industry and promoted the development of green textile finishing. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrospray-assisted encapsulation of caffeine in alginate microhydrogels.

PubMed

Nikoo, Alireza Mehregan; Kadkhodaee, Rassoul; Ghorani, Behrouz; Razzaq, Hussam; Tucker, Nick

2018-05-02

One of the major challenges with microencapsulation and delivery of low molecular weight bioactive compounds is their diffusional loss during storage and process conditions as well as under gastric conditions. In an attempt to slow down the release rate of core material, electrospray fabricated calcium alginate microhydrogels were coated with low molecular weight and high molecular weight chitosans. Caffeine as a hydrophilic model compound was used due to its several advantages on human behavior especially increasing consciousness. Mathematical modeling of the caffeine release by fitting the data with Korsmeyer-Peppas model showed that Fick's diffusion law could be the prevalent mechanism of the release. Electrostatic interaction between alginate and chitosan (particularly in the presence of 1% low molecular weight chitosan) provided an effective barrier against caffeine release and significantly reduced swelling of particles compared to control samples. The results of this study demonstrated that calcium alginate microhydrogels coated by chitosan could be used for encapsulation of low molecular compounds. However, more complementary research must be done in this field. In addition, electrospray, by producing monodisperse particles, would be as an alternative method for fabrication of microparticles based on natural polymers. Copyright © 2018. Published by Elsevier B.V.

Development and evaluation of floating alginate microspheres for oral delivery of anthocyanins - A preliminary investigation.

PubMed

Celli, Giovana B; Ghanem, Amyl; Brooks, Marianne S

2017-05-01

The goal of this study was to develop floating microspheres that could be used as gastroretentive systems for the delivery of anthocyanins (ACNs). These compounds are absorbed in the stomach and small intestine, and insufficient residence time in these organs could result in limited absorption and contribute to degradation. The microparticles containing freeze-dried haskap berry extract (321.96 ± 8.35 mg cyanidin 3-glucoside equivalents per g) were prepared by ionotropic gelation of alginate (9%, w/w) with calcium ions (CaCl 2 at 2%, w/v) in the gelation bath, with calcium carbonate as the gas-generating compound (added at different ratios in the alginate/extract mixture). The effect of acetic acid concentration (2 and 10%, v/v) in the gelation medium was investigated. Increasing the carbonate : alginate weigh ratio from 0 to 3:4 resulted in different degrees of floatability, larger particles, higher encapsulation efficiency, and lower amount of ACN released. The power law equation fitted the experimental data well, indicating that release occurred mainly by diffusion. This is the first time floating microspheres are proposed as gastroretentive platforms for the delivery of ACNs.

Composite microparticles of halloysite clay nanotubes bound by calcium carbonate.

PubMed

Jin, Yi; Yendluri, Raghuvara; Chen, Bin; Wang, Jingbo; Lvov, Yuri

2016-03-15

Natural halloysite clay nanotubes with 15 nm inner and 75 nm outer diameters have been used as vehicles for sustained release of drugs in composite hollow microparticles "glued" with CaCO3. We used a layer-by layer assembly accomplished alginate binding with Ca(2+) followed by CO2 bubbling to prepare the composite microspheres of CaCO3 and polyelectrolytes (PE) modified halloysite nanotubes (HNTs-PE2/CaCO3) with the diameter of about 5-10 μm. These microparticles have empty spherical structure and abundant pore distributions with maxima at 2.5, 3.9, 6.0 and 13.3 nm, and higher surface area of 82.3 m(2) g(-1) as characterized by SEM and BET test. We loaded drugs in these micro-nano carriers of tight piles of halloysite nanotube with end clogged with CaCO3. The sustained release of Nifedipine drug from HNTs-PE2/CaCO3 composite microspheres was slower than for pristine halloysite nanotubes. Copyright © 2015 Elsevier Inc. All rights reserved.

A Microparticle/Hydrogel Combination Drug-Delivery System for Sustained Release of Retinoids

PubMed Central

Gao, Song-Qi; Maeda, Tadao; Okano, Kiichiro; Palczewski, Krzysztof

2012-01-01

Purpose. To design and develop a drug-delivery system containing a combination of poly(d,l-lactide-co-glycolide) (PLGA) microparticles and alginate hydrogel for sustained release of retinoids to treat retinal blinding diseases that result from an inadequate supply of retinol and generation of 11-cis-retinal. Methods. To study drug release in vivo, either the drug-loaded microparticle–hydrogel combination was injected subcutaneously or drug-loaded microparticles were injected intravitreally into Lrat−/− mice. Orally administered 9-cis-retinoids were used for comparison and drug concentrations in plasma were determined by HPLC. Electroretinography (ERG) and both chemical and histologic analyses were used to evaluate drug effects on visual function and morphology. Results. Lrat−/− mice demonstrated sustained drug release from the microparticle/hydrogel combination that lasted 4 weeks after subcutaneous injection. Drug concentrations in plasma of the control group treated with the same oral dose rose to higher levels for 6−7 hours but then dropped markedly by 24 hours. Significantly increased ERG responses and a markedly improved retinal pigmented epithelium (RPE)–rod outer segment (ROS) interface were observed after subcutaneous injection of the drug-loaded delivery combination. Intravitreal injection of just 2% of the systemic dose of drug-loaded microparticles provided comparable therapeutic efficacy. Conclusions. Sustained release of therapeutic levels of 9-cis-retinoids was achieved in Lrat−/− mice by subcutaneous injection in a microparticle/hydrogel drug-delivery system. Both subcutaneous and intravitreal injections of drug-loaded microparticles into Lrat−/− mice improved visual function and retinal structure. PMID:22918645

Comparison of ionic and non-ionic drug release from multi-membrane spherical aerogels.

PubMed

Veronovski, Anja; Knez, Zeljko; Novak, Zoran

2013-09-15

The presented research was oriented towards the preparation of dry biodegradable alginate aerogels with multi-membranes using a multi-step sol-gel process with potential applications as carriers during oral drug delivery. First alginate spherical hydrogels were formed in CaCl2 or BaCl2 solutions by ionic cross-linking. These cores were further immersed into alginate sodium solution, filtered through a sieve, and dropped into the salt solution again. Multi-membrane hydrogels were obtained by repeating the above process. They were further converted into aerogels by supercritical drying. The effect of the number of membranes was investigated regarding the loading and release of the model drugs nicotinic acid and theophylline. Moreover, the efficiencies of Ba(2+) and Ca(2+) metal ions for forming tridimensional networks that retain and extend drug release were also investigated. Nicotinic acid release was prolonged by adding membranes around the core and using Ca(2+) for cross-linking. However, retarded theophylline release was only obtained by using Ba(2+) for cross-linking. Namely, by increasing the number of membranes and BaCl2 concentration drug release became linear versus time in all studied cases. In the case of nicotinic acid loading increased by adding membranes around the core, however, for theophylline the opposite results were obtained due to the different nature of the model drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

Deformable microparticles with multiple functions for drug delivery and device testing

NASA Astrophysics Data System (ADS)

Thula, Taili T.

Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of bioactive agents for the proposed delivery system.

In Situ Forming, Cytocompatible, and Self-Recoverable Tough Hydrogels Based on Dual Ionic and Click Cross-Linked Alginate.

PubMed

Ghanian, Mohammad Hossein; Mirzadeh, Hamid; Baharvand, Hossein

2018-05-14

A dual cross-linking strategy was developed to answer the urgent need for fatigue-resistant, cytocompatible, and in situ forming tough hydrogels. Clickable, yet calcium-binding derivatives of alginate were synthesized by partial substitution of its carboxyl functionalities with furan, which could come into Diels-Alder click reaction with maleimide end groups of a four arm poly(ethylene glycol) cross-linker. Tuning the cooperative viscoelastic action of transient ionic and permanent click cross-links within the single network of alginate provided a soft tough hydrogel with a set of interesting features: (i) immediate self-recovery under cyclic loading, (ii) highly efficient and autonomous self-healing upon fracture, (iii) in situ forming ability for molding and minimally invasive injection, (iv) capability for viable cell encapsulation, and (v) reactivity for on-demand biomolecule conjugation. The facile strategy is applicable to a wide range of natural and synthetic polymers by introducing the calcium binding and click reacting functional groups and can broaden the use of tough hydrogels in load-bearing, cell-laden applications such as soft tissue engineering and bioactuators.

Thermo-controlled rheology of electro-assembled polyanionic polysaccharide (alginate) and polycationic thermo-sensitive polymers.

PubMed

Niang, Pape Momar; Huang, Zhiwei; Dulong, Virginie; Souguir, Zied; Le Cerf, Didier; Picton, Luc

2016-03-30

Several thermo-sensitive polyelectrolyte complexes were prepared by ionic self-association between an anionic polysaccharide (alginate) and a monocationic copolymer (polyether amine, Jeffamine®-M2005) with a 'Low Critical Solubility Temperature' (LCST). We show that electro-association must be established below the aggregation temperature of the free Jeffamine®, after which the organization of the system is controlled by the thermo-association of Jeffamine® that was previously electro-associated with the alginate. Evidence for this comes primarily from the rheology in the semi-dilute region. Electro- and thermo-associative behaviours are optimal at a pH corresponding to maximum ionization of both compounds (around pH 7). High ionic strength could prevent the electro-association. The reversibility of the transition is possible only at temperatures lower than the LCST of Jeffamine®. Similar behaviour has been obtained with carboxymethyl cellulose (CMC), which suggests that this behaviour can be observed using a range of anionic polyelectrolytes. In contrast, no specific properties have been found for pullulan, which is a neutral polysaccharide. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microencapsulation of rifampicin: A technique to preserve the mechanical properties of bone cement.

PubMed

Sanz-Ruiz, Pablo; Carbó-Laso, Esther; Del Real-Romero, Juan Carlos; Arán-Ais, Francisca; Ballesteros-Iglesias, Yolanda; Paz-Jiménez, Eva; Sánchez-Navarro, Magdalena; Pérez-Limiñana, María Ángeles; Vaquero-Martín, Javier

2018-01-01

Two-stage exchange with antibiotic-loaded bone cement spacers remains the gold standard for chronic periprosthetic joint infection (PJI). Rifampicin is highly efficient on stationary-phase staphylococci in biofilm; however, its addition to PMMA to manufacture spacers prevents polymerization and reduces mechanical properties. Isolation of rifampicin during polymerization by microencapsulation could allow manufacturing rifampicin-loaded bone cement maintaining elution and mechanical properties. Microcapsules of rifampicin with alginate, polyhydroxybutyratehydroxyvalerate (PHBV), ethylcellulose and stearic acid (SA) were synthesized. Alginate and PHBV microcapsules were added to bone cement and elution, compression, bending, hardness, setting time and microbiological tests were performed. Repeated measures ANOVA and Bonferroni post-hoc test were performed, considering a p < 0.05 as statistical significance. Bone cement specimens containing alginate microcapsules eluted more rifampicin than PHBV microcapsules or non-encapsulated rifampicin over time (p < 0.012). Microencapsulation of rifampicin allowed PMMA to preserve mechanical properties in compression and bending tests. Cement with alginate microcapsules showed similar behavior in hardness tests to control cement over the study period (73 ± 1.68H D ). PMMA with alginate microcapsules exhibited the largest zones of inhibition in microbiological tests. Statistically significant differences in mean diameters of zones of inhibition between PMMA loaded with alginate-rifampicin (p = 0.0001) and alginate-PHBV microcapsules (p = 0.0001) were detected. Rifampicin microencapsulation with alginate is the best choice to introduce rifampicin in PMMA preserving mechanical properties, setting time, elution, and antimicrobial properties. The main applicability of this study is the opportunity for obtaining rifampicin-loaded PMMA by microencapsulation of rifampicin in alginate microparticles, achieving high doses of rifampicin in infected tissues, increasing the successful of PJI treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:459-466, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Molecular interactions in self-assembled nano-structures of chitosan-sodium alginate based polyelectrolyte complexes.

PubMed

Wasupalli, Geeta Kumari; Verma, Devendra

2018-03-16

We report here the self-assembled structures of polyelectrolyte complexes (PECs) of polyanionic sodium alginate with the polycationic chitosan at room temperature. The PECs prepared at different pH values exhibited two distinct morphologies. The chitosan-alginate PECs self-assembled into the fibrous structure in a low pH range of pH3 to 7. The PECs obtained at high pH series around pH8 and above resulted in the formation of colloidal nanoparticles in the range of 120±9.48nm to 46.02±16.66nm. The zeta potential measurement showed that PECs prepared at lower pH (pH<6) exhibited nearly neutral surface charge, whereas PECs prepared at higher pH than 6 exhibited highly negative surface charge. The molecular interactions in nano-colloids and fibers were evaluated using FTIR analysis. The results attest that the ionic state of the chitosan and alginate plays an important role controlling the morphologies of the PECS. The present study has identified the enormous potential of the polyelectrolytes complexes to exploit shape by the alteration of ionic strength. These findings might be useful in the development of novel biomaterial. The produced fibers and nanocolloids could be applied as a biomaterial for tissue engineering and drug delivery. Copyright © 2017. Published by Elsevier B.V.

Diffusion Control in the in Situ Synthesis of Iconic Metal-Organic Frameworks within an Ionic Polymer Matrix.

PubMed

Lim, Jungho; Lee, Eun Ji; Choi, Jae Sun; Jeong, Nak Cheon

2018-01-31

Ionic polymers that possess ion-exchangeable sites have been shown to be a greatly useful platform to fabricate mixed matrices (MMs) where metal-organic frameworks (MOFs) can be in situ synthesized, although the in situ synthesis of MOF has been rarely studied. In this study, alginate (ALG), an anionic green polymer that possesses metal-ion-exchangeable sites, is employed as a platform of MMs for the in situ synthesis of iconic MOFs, HKUST-1, and MOF-74(Zn). We demonstrate for the first time that the sequential order of supplying MOF ingredients (metal ion and deprotonated ligand) into the alginate matrix leads to substantially different results because of a difference in the diffusion of the MOF components. For the examples examined, whereas the infusion of BTC 3- ligand into Cu 2+ -exchanged ALG engendered the eggshell-shaped HKUST-1 layers on the surface of MM spheres, the infusion of Cu 2+ ions into BTC 3- -included alginate engendered the high dispersivity and junction contact of HKUST-1 crystals in the alginate matrix. This fundamental property has been exploited to fabricate a flexible MOF-containing mixed matrix membrane by coincorporating poly(vinyl alcohol). Using two molecular dyes, namely, methylene blue and rhodamine 6G, further, we show that this in situ strategy is suitable for fabricating an MOF-MM that exhibits size-selective molecular uptake.

Enhancement of thermal transport in Gel Polymer Electrolytes with embedded BN/Al2O3 nano- and micro-particles

NASA Astrophysics Data System (ADS)

Vishwakarma, Vivek; Jain, Ankur

2017-09-01

While Gel Polymer Electrolytes (GPEs) have been widely investigated for use in next-generation Li-ion cells due to the potential for improved thermal safety, thermal transport within a GPE is still poorly understood. Among all materials in a Li-ion cell, the GPE has the lowest thermal conductivity, and hence determines the overall rate of heat flow in a Li-ion cell. This makes it critical to measure and understand thermal transport in a GPE and investigate trade-offs between thermal and ionic transport. This paper presents measurements of thermal and ionic conductivities in a PVdF-based GPE. The effect of incorporating BN/Al2O3 ceramic nano/microparticles in the GPE on thermal and ionic transport is characterized. Measurements indicate up to 2.5X improvement in thermal conductivity of activated GPE membranes, with relatively minor effect on electrochemical performance of GPE-based single-layer cells. The measured enhancement in thermal conductivity is in very good agreement with theoretical calculations based on the effective medium theory that accounts for thermal transport in a dispersed, two-phase medium such as a GPE. The fundamental insights gained in this work on thermal transport in a GPE and the role of nano/microparticle inclusions may facilitate thermal-electrochemical optimization and design of GPEs for safe, high-performance Li-ion cells.

Fabrication and characterization of carboxymethyl cellulose novel microparticles for bone tissue engineering.

PubMed

Gaihre, Bipin; Jayasuriya, Ambalangodage C

2016-12-01

In this study we developed carboxymethyl cellulose (CMC) microparticles through ionic crosslinking with the aqueous ion complex of zirconium (Zr) and further complexing with chitosan (CS) and determined the physio-chemical and biological properties of these novel microparticles. In order to assess the role of Zr, microparticles were prepared in 5% and 10% (w/v) zirconium tetrachloride solution. Scanning electron microscopy (SEM) with energy dispersive X-ray spectrometer (EDS) results showed that Zr was uniformly distributed on the surface of the microparticles as a result of which uniform groovy surface was obtained. We found that Zr enhances the surface roughness of the microparticles and stability studies showed that it also increases the stability of microparticles in phosphate buffered saline. The crosslinking of anionic CMC with cationic Zr and CS was confirmed by Fourier transform infrared spectroscopy (FTIR) results. The response of murine pre-osteoblasts (OB-6) when cultured with microparticles was investigated. Live/dead cell assay showed that microparticles did not induce any cytotoxic effects as cells were attaching and proliferating on the well plate as well as along the surface of microparticles. In addition, SEM images showed that microparticles support the attachment of cells and they appeared to be directly interacting with the surface of microparticle. Within 10days of culture most of the top surface of microparticles was covered with a layer of cells indicating that they were proliferating well throughout the surface of microparticles. We observed that Zr enhances the cell attachment and proliferation as more cells were present on microparticles with 10% Zr. These promising results show the potential applications of CMC-Zr microparticles in bone tissue engineering. Copyright © 2016 Elsevier B.V. All rights reserved.

Which iodinated contrast media is the least cytotoxic to human disc cells?

PubMed

Kim, Kyung-Hyun; Park, Jeong-Yoon; Park, Hyo-Suk; Kuh, Sung-Uk; Chin, Dong-Kyu; Kim, Keun-Su; Cho, Yong-Eun

2015-05-01

Iodinated contrast media (CM) is commonly used for various intradiscal injections such as in discography and endoscopic spinal surgery. However, CM has been shown to be toxic to renal tissue due to its ionic strength and osmolarity and as a result of iodine-induced cytotoxicity, which has raised concern over whether there are similar negative effects on disc cells. This in vitro study was designed to identify the least cytotoxic iodinated CM to the human disc cell among four different physiochemical iodinated contrast dyes. In vitro laboratory study. Intervertebral disc tissue was obtained by discectomy from a total of 10 lumbar disc patients undergoing surgery and disc cells were isolated. The human disc cells were grown in 3D alginate bead culture with 0, 0.1, 10, and 100 mg/mL CM solutions (ionic dimer, ionic monomer, non-ionic dimer, and non-ionic monomer) and mannitol as a control for 2 days. The living cells were analyzed with trypan blue staining. Fluorescence-activated cell sorting analysis was performed using Annexin V and propidium iodide (PI) and 3D alginate bead immunostaining to identify live, apoptotic, and necrotic cells. Human disc cell death was time- and dose-dependent in response to CM and more necrosis was observed than apoptosis. In addition, non-ionic dimeric CM (iodixanol) showed the least toxic effect on human disc cells, followed by non-ionic monomeric (iopromide), ionic dimeric (ioxaglate), and ionic monomeric CM (ioxithalamate). Contrast media is cytotoxic to human disc cells in a dose- and time-dependent manner. This in vitro study revealed that, among four different CM preparations, non-ionic dimeric CM is the least detrimental to human disc cell viability. Careful attention should be paid to the type of CM chosen for discography and endoscopic spinal surgery. It is also necessary to investigate the detrimental effects of CM on disc cells and disc degeneration in further in vivo studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Fabrication of monodispersive nanoscale alginate-chitosan core-shell particulate systems for controlled release studies

NASA Astrophysics Data System (ADS)

Körpe, Didem Aksoy; Malekghasemi, Soheil; Aydın, Uğur; Duman, Memed

2014-12-01

Biopolymers such as chitosan and alginate are widely used for controlled drug delivery systems. The present work aimed to develop a new protocol for preparation of monodisperse alginate-coated chitosan nanoparticles at nanoscale. Modifications of preparation protocol contain changing the pH of polymer solutions and adding extra centrifugation steps into the procedure. While chitosan nanoparticles were synthesized by ionic gelation method, they were coated with alginate by electrostatic interaction. The size, morphology, charge, and structural characterization of prepared core-shell nanoparticulated system were performed by AFM, Zeta sizer, and FTIR. BSA and DOX were loaded as test biomolecules to core and shell part of the nanoparticle, respectively. Release profiles of BSA and DOX were determined by spectrophotometry. The sizes of both chitosan and alginate-coated chitosan nanoparticles which were prepared by modified protocol were measured to be 50 ± 10 and 60 ± 3 nm, respectively. After loading BSA and DOX, the average size of the particles increased to 80 ± 7 nm. Moreover, while the zeta potential of chitosan nanoparticles was positive value, the value was inverted to negative after alginate coating. Release profile measurements of BSA and DOX were determined during 57 and 2 days, respectively. Our results demonstrated that monodisperse alginate-coated nanoparticles were synthesized and loaded successfully using our modified protocol.

Particle self-assembly at ionic liquid-based interfaces.

PubMed

Frost, Denzil S; Nofen, Elizabeth M; Dai, Lenore L

2014-04-01

This review presents an overview of the nature of ionic liquid (IL)-based interfaces and self-assembled particle morphologies of IL-in-water, oil- and water-in-IL, and novel IL-in-IL Pickering emulsions with emphasis on their unique phenomena, by means of experimental and computational studies. In IL-in-water Pickering emulsions, particles formed monolayers at ionic liquid-water interfaces and were close-packed on fully covered emulsion droplets or aggregated on partially covered droplets. Interestingly, other than equilibrating at the ionic liquid-water interfaces, microparticles with certain surface chemistries were extracted into the ionic liquid phase with a high efficiency. These experimental findings were supported by potential of mean force calculations, which showed large energy drops as hydrophobic particles crossed the interface into the IL phase. In the oil- and water-in-IL Pickering emulsions, microparticles with acidic surface chemistries formed monolayer bridges between the internal phase droplets rather than residing at the oil/water-ionic liquid interfaces, a significant deviation from traditional Pickering emulsion morphology. Molecular dynamics simulations revealed aspects of the mechanism behind this bridging phenomenon, including the role of the droplet phase, surface chemistry, and inter-particle film. Novel IL-in-IL Pickering emulsions exhibited an array of self-assembled morphologies including the previously observed particle absorption and bridging phenomena. The appearance of these morphologies depended on the particle surface chemistry as well as the ILs used. The incorporation of particle self-assembly with ionic liquid science allows for new applications at the intersection of these two fields, and have the potential to be numerous due to the tunability of the ionic liquids and particles incorporated, as well as the particle morphology by combining certain groups of particle surface chemistry, IL type (protic or aprotic), and whether oil or water is incorporated. © 2013.

Micro-Encapsulated Porphyrins and Phthalocyanines - New Formulations in Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Ion, R. M.

2017-06-01

Photodynamic therapy (PDT), as an innovative method for cancer tretament is based on a concerted action of some drugs, called sensitizers, which generate reactive oxygen species via a photochemical mechanism, leading to cellular necrosis or apoptosis. The present work aims at loading some sensitizers, as porphyrins (P) and phthalocyanines (Pc) into alginate particles. Particles were prepared by dropping alginate into an aqueous solution containing P or Pc and CaCl2, which allows the formation of particles through ionic crosslinking. It was obtained P or Pc loaded alginate beads with an average diameter of about 100 μm. For these systems, this paper analyses the spectroscopic properties, encapsulation into microcapsules, controlled releasing action and their photosensitizer capacity (singlet oxygen generation).

Development of alginate microspheres containing thyme essential oil using ionic gelation.

PubMed

Benavides, Sergio; Cortés, Pablo; Parada, Javier; Franco, Wendy

2016-08-01

Essential oils are a good antimicrobial and antioxidant agent alternative in human or animal feed. However, their direct use has several disadvantages such as volatilization or oxidation. The development of essential oil microspheres may help to avoid these problems. The objective of the present research was to microencapsulate thyme essential oil by generating emulsions with different dispersion degrees. The emulsions were encapsulated in calcium-alginate microspheres by ionic gelation. The microspheres were evaluated regarding size, shape, encapsulation efficiency, loading capacity and antimicrobial properties. The results indicate that encapsulation efficiency and loading capacity are dependent on concentration and degree of dispersion. The best encapsulation conditions were obtained at 2% v/v of thyme essential oil with a high dispersion degree (18,000rpm/5min), which was achieved with an efficiency of 85%. Finally, the microspheres obtained showed significant antimicrobial effect, especially in gram-positive bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improvement of stability of oil-in-water emulsions containing caseinate-coated droplets by addition of sodium alginate.

PubMed

Pallandre, S; Decker, E A; McClements, D J

2007-11-01

The potential of sodium alginate for improving the stability of emulsions containing caseinate-coated droplets was investigated. One wt% corn oil-in-water emulsions containing anionic caseinate-coated droplets (0.15 wt% sodium caseinate) and anionic sodium alginate (0 to 1 wt%) were prepared at pH 7. The pH of these emulsions was then adjusted to 3.5, so that the anionic alginate molecules adsorbed to the cationic caseinate-coated droplets. Extensive droplet aggregation occurred when there was insufficient alginate to completely saturate the droplet surfaces due to bridging flocculation, and when the nonadsorbed alginate concentration was high enough to induce depletion flocculation. Emulsions with relatively small particle sizes could be formed over a range of alginate concentrations (0.1 to 0.4 wt%). The influence of pHs (3 to 7) and sodium chloride (0 to 500 mM) on the properties of primary (0 wt% alginate) and secondary (0.15 wt% alginate) emulsions was studied. Alginate adsorbed to the droplet surfaces at pHs 3, 4, and 5, but not at pHs 6 and 7, due to electrostatic attraction between anionic groups on the alginate and cationic groups on the adsorbed caseinate. Secondary emulsions had better stability than primary emulsions at pH values near caseinate's isoelectric point (pHs 4 and 5). In addition, secondary emulsions were stable up to higher ionic strengths (< 300 mM) than primary emulsions (<50 mM). The controlled electrostatic deposition method utilized in this study could be used to extend the range of application of dairy protein emulsifiers in the food industry.

Chelators influenced synthesis of chitosan-carboxymethyl cellulose microparticles for controlled drug delivery

NASA Astrophysics Data System (ADS)

Samrot, Antony V.; Akanksha; Jahnavi, Tatipamula; Padmanaban, S.; Philip, Sheryl-Ann; Burman, Ujjala; Rabel, Arul Maximus

2016-11-01

In this study, polyphenolic curcumin is entrapped within microcomposites made of biopolymers chitosan (CS) and carboxymethyl cellulose (CMC) formulated by ionic gelation method. Here, different concentrations of two chelating agents, barium chloride and sodium tripolyphosphate, are used to make microcomposites. Thus, the synthesized microparticles were characterized by FTIR, and their surface morphology was studied by SEM. Drug encapsulation efficiency and the drug release kinetics of CS-CMC composites are also studied. The produced microcomposites were used to study antibacterial activity in vitro.

Core-shell alginate-ghatti gum modified montmorillonite composite matrices for stomach-specific flurbiprofen delivery.

PubMed

Bera, Hriday; Ippagunta, Sohitha Reddy; Kumar, Sanoj; Vangala, Pavani

2017-07-01

Novel alginate-arabic gum (AG) gel membrane coated alginate-ghatti gum (GG) modified montmorillonite (MMT) composite matrices were developed for intragastric flurbiprofen (FLU) delivery by combining floating and mucoadhesion mechanisms. The clay-biopolymer composite matrices containing FLU as core were accomplished by ionic-gelation technique. Effects of polymer-blend (alginate:GG) ratios and crosslinker (CaCl 2 ) concentrations on drug entrapment efficiency (DEE, %) and cumulative drug release after 8h (Q 8h , %) were studied to optimize the core matrices by a 3 2 factorial design. The optimized matrices (F-O) demonstrated DEE of 91.69±1.43% and Q 8h of 74.96±1.56% with minimum errors in prediction. The alginate-AG gel membrane enveloped optimized matrices (F-O, coated) exhibited superior buoyancy, better ex vivo mucoadhesion and slower drug release rate. The drug release profile of FLU-loaded uncoated and coated optimized matrices was best fitted in Korsmeyer-Peppas model with anomalous diffusion and case-II transport driven mechanism, respectively. The uncoated and coated matrices containing FLU were also characterized for drug-excipients compatibility, drug crystallinity, thermal behaviour and surface morphology. Thus, the newly developed alginate-AG gel membrane coated alginate-GG modified MMT composite matrices are appropriate for intragastric delivery of FLU over an extended period of time with improved therapeutic benefits. Copyright © 2017 Elsevier B.V. All rights reserved.

Outstanding features of alginate-based gel electrolyte with ionic liquid for electric double layer capacitors

NASA Astrophysics Data System (ADS)

Soeda, Kazunari; Yamagata, Masaki; Ishikawa, Masashi

2015-04-01

An alginate-based gel electrolyte with an ionic liquid (Alg/IL) is investigated for electric double-layer capacitors (EDLCs) by using physicochemical and electrochemical measurements. The Alg/EMImBF4 (EMImBF4 = 1-ethyl-3-methylimidazolium tetrafluoroborate) gel electrolyte is thermally stable up to 280 °C, where EMImBF4 decomposes. Furthermore, the EDLC with the gel electrolyte can be operated even at high temperature. The cell containing Alg/EMImBF4 is also electrochemically stable even under high voltage (∼3.5 V) operation. Thus, the alginate is a suitable host polymer for the gel electrolyte for EDLCs. According to the result of charge-discharge characteristics, the voltage drop in the charge-discharge curve for the cell with Alg/EMImBF4 gel electrolyte is considerably smaller than that with liquid-phase EMImBF4 electrolyte. To clarify the effect of Alg in contact with the activated carbon electrode, we also prepared an Alg-containing ACFC electrode (Alg + ACFC), and evaluated its EDLC characteristics in liquid EMImBF4. The results prove that the presence of Alg close to the active materials significantly reduces the internal resistance of the EDLC cell, which may be attributed to the high affinity of Alg to activated carbon.

Sustainable and Superior Heat-Resistant Alginate Nonwoven Separator of LiNi0.5Mn1.5O4/Li Batteries Operated at 55 °C.

PubMed

Wen, Huijie; Zhang, Jianjun; Chai, Jingchao; Ma, Jun; Yue, Liping; Dong, Tiantian; Zang, Xiao; Liu, Zhihong; Zhang, Botao; Cui, Guanglei

2017-02-01

High-voltage lithium-ion batteries have become a major research focus. As a major part of lithium batteries, the separator plays a critical role in the development of high-voltage lithium batteries. Herein, we demonstrated a sustainable and superior heat-resistant alginate nonwoven separator for high-voltage (5 V) lithium batteries. It was demonstrated that the resultant alginate nonwoven separator exhibited better mechanical property (37 MPa), superior thermal stability (up to 150 °C), and higher ionic conductivity (1.4 × 10 -3 S/cm) as compared to commercially available polyolefin (PP) separator. More impressively, the 5 V class LiNi 0.5 Mn 1.5 O 4 (LNMO)/Li cell with this alginate nonwoven separator delivered much better cycling stability (maintaining 79.6% of its initial discharge capacity) than that (69.3%) of PP separator after 200 cycles at an elevated temperature of 55 °C. In addition, the LiFePO 4 /Li cell assembled with such alginate nonwoven separator could still charge and discharge normally even at an elevated temperature of 150 °C. The above-mentioned fascinating characteristics of alginate separator provide great probability for its application for high-voltage (5 V) lithium batteries at elevated temperatures.

Protease-functionalized mucus penetrating microparticles: In-vivo evidence for their potential.

PubMed

Mahmood, Arshad; Laffleur, Flavia; Leonaviciute, Gintare; Bernkop-Schnürch, Andreas

2017-10-30

The focus of the current study was to explore whether immobilization of proteases to microparticles could result in their enhanced penetration into mucus. The proteases papain (PAP) and bromelain (BROM) were covalently attached to a polyacrylate (PAA; Carbopol 971P) via amide bond formation based on carbodiimide reaction. Microparticles containing these conjugates were generated via ionic gelation with calcium chloride and were characterized regarding size, surface charge, enzymatic activity and fluorescein diacetate (FDA) loading efficiency. Furthermore, mucus penetration potential of these microparticles was evaluated in-vitro on freshly collected porcine intestinal mucus, on intact intestinal mucosa and in-vivo in Sprague-Dawley rats. Results showed mean diameter of microparticles ranging between 2-3μm and surface charge between -8 to -18mV. The addition of PAA-microparticles to porcine intestinal mucus led to a 1.39-fold increase in dynamic viscosity whereas a 3.10- and 2.12-fold decrease was observed in case of PAA-PAP and PAA-BROM microparticles, respectively. Mucus penetration studies showed a 4.27- and 2.21- fold higher permeation of FDA loaded PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. Extent of mucus diffusion determined via silicon tube assay illustrated 3.96- fold higher penetration for PAA-PAP microparticles and 1.99- fold for PAA-BROM microparticles. An in-vitro analysis on porcine intestinal mucosa described up to 16- and 7.35-fold higher degree of retention and furthermore, during in-vivo evaluation in Sprague-Dawley rats a 3.35- and 2.07-fold higher penetration behavior was observed in small intestine for PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. According to these results, evidence for microparticles decorated with proteases in order to overcome the mucus barrier and to reach the absorption lining has been provided that offers wide ranging applications in mucosal drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Improvement of Biodesulfurization Rate of Alginate Immobilized Rhodococcus erythropolis R1

PubMed Central

Derikvand, Peyman; Etemadifar, Zahra

2014-01-01

Background: Sulfur oxides released from the burning of oil causes severe environmental pollution. The sulfur can be removed via the 4S pathway in biodesulfurization (BDS). Immobilization approaches have been developed to prevent cell contamination of oil during the BDS process. Objectives: The encapsulation of Rhodococcus erythropolis R1 in calcium alginate beads was studied in order to enhance conversion of dibenzothiophene (DBT) to 2-hydroxy biphenyl (2-HBP) as the final product. Also the effect of different factors on the BDS process was investigated. Materials and Methods: Calcium alginate capsules were prepared using peristaltic pumps with different needle sizes to control the beads sizes. Scanning electron microscopy and flow cytometry methods were used to study the distribution and viability of encapsulated cells, respectively. Two non-ionic surfactants and also nano Ƴ-Al2O3were used with the ratio of 0.5% (v/v) and 1:5 (v/v) respectively to investigate their BDS efficiency. In addition, the effect of different bead sizes and different concentrations of sodium alginate in BDS activity was studied. Results: The 2% (w/v) sodium alginate beads with 1.5mm size were found to be the optimum for beads stability and efficient 2-HBP production. The viability of encapsulated cells decreased by 12% after 20 h of desulfurization, compared to free cells. Adding the non-ionic surfactants markedly enhanced the rate of BDS, because of increasing mass transfer of DBT to the gel matrix. In addition, Span 80 was more effective than Tween 80. The nanoƳ-Al2O3 particles could increase BDS rate by up to two-folds greater than that of the control beads. Conclusions: The nano Ƴ-Al2O3 can improve the immobilized biocatalyst for excellent efficiency of DBT desulfurization. Also the BDS activity can be enhanced by setting the other explained factors at optimum levels. PMID:25147685

Improvement of Biodesulfurization Rate of Alginate Immobilized Rhodococcus erythropolis R1.

PubMed

Derikvand, Peyman; Etemadifar, Zahra

2014-03-01

Sulfur oxides released from the burning of oil causes severe environmental pollution. The sulfur can be removed via the 4S pathway in biodesulfurization (BDS). Immobilization approaches have been developed to prevent cell contamination of oil during the BDS process. The encapsulation of Rhodococcus erythropolis R1 in calcium alginate beads was studied in order to enhance conversion of dibenzothiophene (DBT) to 2-hydroxy biphenyl (2-HBP) as the final product. Also the effect of different factors on the BDS process was investigated. Calcium alginate capsules were prepared using peristaltic pumps with different needle sizes to control the beads sizes. Scanning electron microscopy and flow cytometry methods were used to study the distribution and viability of encapsulated cells, respectively. Two non-ionic surfactants and also nano Ƴ-Al2O3were used with the ratio of 0.5% (v/v) and 1:5 (v/v) respectively to investigate their BDS efficiency. In addition, the effect of different bead sizes and different concentrations of sodium alginate in BDS activity was studied. The 2% (w/v) sodium alginate beads with 1.5mm size were found to be the optimum for beads stability and efficient 2-HBP production. The viability of encapsulated cells decreased by 12% after 20 h of desulfurization, compared to free cells. Adding the non-ionic surfactants markedly enhanced the rate of BDS, because of increasing mass transfer of DBT to the gel matrix. In addition, Span 80 was more effective than Tween 80. The nanoƳ-Al2O3 particles could increase BDS rate by up to two-folds greater than that of the control beads. The nano Ƴ-Al2O3 can improve the immobilized biocatalyst for excellent efficiency of DBT desulfurization. Also the BDS activity can be enhanced by setting the other explained factors at optimum levels.

Alginate nanoparticles protect ferrous from oxidation: Potential iron delivery system.

PubMed

Katuwavila, Nuwanthi P; Perera, A D L C; Dahanayake, Damayanthi; Karunaratne, V; Amaratunga, Gehan A J; Karunaratne, D Nedra

2016-11-20

A novel, efficient delivery system for iron (Fe 2+ ) was developed using the alginate biopolymer. Iron loaded alginate nanoparticles were synthesized by a controlled ionic gelation method and was characterized with respect to particle size, zeta potential, morphology and encapsulation efficiency. Successful loading was confirmed with Fourier Transform Infrared spectroscopy and Thermogravimetric Analysis. Electron energy loss spectroscopy study corroborated the loading of ferrous into the alginate nanoparticles. Iron encapsulation (70%) was optimized at 0.06% Fe (w/v) leading to the formation of iron loaded alginate nanoparticles with a size range of 15-30nm and with a negative zeta potential (-38mV). The in vitro release studies showed a prolonged release profile for 96h. Release of iron was around 65-70% at pH of 6 and 7.4 whereas it was less than 20% at pH 2.The initial burst release upto 8h followed zero order kinetics at all three pH values. All the release profiles beyond 8h best fitted the Korsmeyer-Peppas model of diffusion. Non Fickian diffusion was observed at pH 6 and 7.4 while at pH 2 Fickian diffusion was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

Encapsulated eucalyptus oil in ionically cross-linked alginate microcapsules and its controlled release.

PubMed

Noppakundilograt, Supaporn; Piboon, Phianghathai; Graisuwan, Wilaiporn; Nuisin, Roongkan; Kiatkamjornwong, Suda

2015-10-20

Sodium alginate microcapsules containing eucalyptus oil were prepared by oil-in-water emulsification via Shirasu porous glass (SPG) membrane and cross-linked by calcium chloride (CaCl2). SPG membrane pore size of 5.2μm was used to control the size of eucalyptus oil microdroplets. Effects of sodium alginate, having a mannuronic acid/guluronic acid (M/G) ratio of 1.13, eucalyptus oil and CaCl2 amounts on microdroplet sizes and size distribution were elucidated. Increasing sodium alginate amounts from 0.1 to 0.5% (wv(-1)) sodium alginate, the average droplets size increased from 42.2±2.0 to 48.5±0.6μm, with CVs of 16.5±2.2 and 30.2±4.5%, respectively. CaCl2 successfully gave narrower size distribution of cross-linked eucalyptus oil microcapsules. The optimum conditions for preparing the microcapsules, oil loading efficiency, and controlled release of the encapsulated eucalyptus oil from the microcapsules as a function of time at 40°C were investigated. Release model for the oil from microcapsules fitted Ritger-Peppas model with non-Fickian transport mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Granular gel support-enabled extrusion of three-dimensional alginate and cellular structures.

PubMed

Jin, Yifei; Compaan, Ashley; Bhattacharjee, Tapomoy; Huang, Yong

2016-06-03

Freeform fabrication of soft structures has been of great interest in recent years. In particular, it is viewed as a critical step toward the grand vision of organ printing--the on-demand design and fabrication of three-dimensional (3D) human organ constructs for implantation and regenerative medicine. The objective of this study is to develop a novel granular gel support material-enabled, two-step gelation-based 'printing-then-gelation' approach to fabricate 3D alginate structures using filament extrusion. Specifically, a granular Carbopol microgel bath holds the ungelled alginate structure being extruded, avoiding the instantaneous gelation of each printed layer as well as resultant surface tension-induced nozzle clogging. Since Carbopol microgels react with multivalent cations, which are needed for alginate crosslinking, gelatin is introduced as a sacrificial material to make an alginate and gelatin bioink for extrusion, which gels thermally (step-one gelation) to initially stabilize the printed structure for removal from Carbopol. Then gelatin is melted and diffused away while alginate is ionically crosslinked in a 37 °C calcium chloride bath (step-two gelation), resulting in an alginate structure. The proposed 'printing-then-gelation' approach works for alginate structure fabrication, and it is also applicable for the printing of cellular constructs and other similar homogeneous soft structures using a two-step or even multi-step approach. The main conclusions are: (1) 0.8% (w/v) Carbopol bath with a neutral pH value may be most suitable for soft structure printing; (2) it is most effective to use a 0.9% (w/v) NaCl solution to facilitate the removal of residual Carbopol; and (3) alginate structures fabricated using the proposed approach demonstrate better mechanical properties than those fabricated using the conventional 'gelation-while-printing' approach.

Encapsulating betalains from Opuntia ficus-indica fruits by ionic gelation: Pigment chemical stability during storage of beads.

PubMed

Otálora, María Carolina; Carriazo, José Gregorio; Iturriaga, Laura; Osorio, Coralia; Nazareno, Mónica Azucena

2016-07-01

Betalain encapsulation was performed by ionic gelation as a stabilization strategy for these natural pigments. Betalains were extracted from purple cactus fruits and encapsulated in calcium-alginate and in combination of calcium alginate and bovine serum albumin. Beads were characterised by scanning electron microscopy and thermal analysis using differential scanning calorimetry and thermogravimetry. Moisture sorption isotherms were determined. Bead morphology was affected by matrix composition. Pigments storage stability was evaluated at different equilibrium relative humidity and temperatures. Pigment composition of beads was determined by HPLC-MS-MS and degradation products were also analysed after storage; betalamic acid being the major one. Both types of matrices protected the encapsulated pigments, being their storage stability better at low relative humidity than that of the non-encapsulated control material. Antiradical activities of beads were proportional to remaining betalain contents. At high relative humidity, there was no protection and low storage stability was observed in the samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Oxidation of alginate and pectate biopolymers by cerium(IV) in perchloric and sulfuric acid solutions: A comparative kinetic and mechanistic study.

PubMed

Fawzy, Ahmed

2016-03-15

The kinetics of oxidation of alginate (Alg) and pectate (Pec) carbohydrate biopolymers was studied by spectrophotometry in aqueous perchloric and sulfuric acid solutions at fixed ionic strengths and temperature. In both acids, the reactions showed a first order dependence on [Ce(IV)], whereas the orders with respect to biopolymer concentrations are less than unity. In perchloric acid, the reactions exhibited less than unit orders with respect to [H(+)] whereas those proceeded in sulfuric acid showed negative fractional-first order dependences on [H(+)]. The effect of ionic strength and dielectric constant was studied. Probable mechanistic schemes for oxidation reactions were proposed. In both acids, the final oxidation products were characterized as mono-keto derivatives of both biopolymers. The activation parameters with respect to the slow step of the mechanisms were computed and discussed. The rate laws were derived and the reaction constants involved in the different steps of the mechanisms were calculated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique.

PubMed

Rodriguez, Lidia B; Avalos, Abraham; Chiaia, Nicholas; Nadarajah, Arunan

2017-05-01

There are many studies about the synthesis of chitosan microparticles; however, most of them have very low production rate, have wide size distribution, are difficult to reproduce, and use harsh crosslinking agents. Uniform microparticles are necessary to obtain repeatable drug release behavior. The main focus of this investigation was to study the effect of the process and formulation parameters during the preparation of chitosan microparticles in order to produce particles with narrow size distribution. The technique evaluated during this study was emulsion crosslinking technique. Chitosan is a biocompatible and biodegradable material but lacks good mechanical properties; for that reason, chitosan was ionically crosslinked with sodium tripolyphosphate (TPP) at three different ratios (32, 64, and 100%). The model drug used was acetylsalicylic acid (ASA). During the preparation of the microparticles, chitosan was first mixed with ASA and then dispersed in oil containing an emulsifier. The evaporation of the solvents hardened the hydrophilic droplets forming microparticles with spherical shape. The process and formulation parameters were varied, and the microparticles were characterized by their morphology, particle size, drug loading efficiency, and drug release behavior. The higher drug loading efficiency was achieved by using 32% mass ratio of TPP to chitosan. The average microparticle size was 18.7 μm. The optimum formulation conditions to prepare uniform spherical microparticles were determined and represented by a region in a triangular phase diagram. The drug release analyses were evaluated in phosphate buffer solution at pH 7.4 and were mainly completed at 24 h.

Microencapsulation of islets within alginate/poly(ethylene glycol) gels cross-linked via Staudinger ligation

PubMed Central

Hall, Kristina K.; Gattás-Asfura, Kerim M.; Stabler, Cherie L.

2010-01-01

Functionalized alginate and PEG polymers were used to generate covalently linked alginate-PEG (XAlgPEG) microbeads of high stability. The cell-compatible Staudinger ligation scheme was used to chemoselectively cross-link phosphine-terminated poly(ethylene glycol) (PEG) to azide-functionalized alginate, resulting in XAlgPEG hydrogels. XAlgPEG microbeads were formed by co-incubation of the two polymers, followed by ionic cross-linking of the alginate using barium ions. The enhanced stability and gel properties of the resulting XAlgPEG microbeads, as well as the compatibility of these polymers for the encapsulation of islets and beta cells lines, were investigated. Our data show that XAlgPEG microbeads exhibit superior resistance to osmotic swelling compared to traditional barium cross-linked alginate (Ba-Alg) beads, with a 5-fold reduction in observed swelling, as well as resistance to dissolution via chelation solution. Diffusion and porosity studies found XAlgPEG beads to exhibit properties comparable to standard Ba-Alg. Our data found XAlgPEG microbeads to be highly cell compatible with insulinoma cell lines, as well as rat and human pancreatic islets, where the viability and functional assessment of cells within XAlgPEG were comparable to Ba-Alg controls. The remarkable improved stability, as well as demonstrated cellular compatibility, of XAlgPEG hydrogels makes them an appealing option for a wide variety of tissue engineering applications. PMID:20654745

Nanocomposite particles with improved microstructure for 3D culture systems and bone regeneration.

PubMed

Cecoltan, Sergiu; Stancu, Izabela-Cristina; Drăguşin, Diana Maria; Serafim, Andrada; Lungu, Adriana; Ţucureanu, Cătălin; Caraş, Iuliana; Tofan, Vlad Constantin; Sălăgeanu, Aurora; Vasile, Eugeniu; Mallet, Romain; Chappard, Daniel; Coman, Cristin; Istodorescu, Mircea; Iovu, Horia

2017-08-31

Nano-apatite and gelatin-alginate hydrogel microparticles have been prepared by a one-step synthesis combined with electrostatic bead generation, for the reconstruction of bone defects. Based on the analysis of bone composition, architecture and embryonic intramembranous ossification, a bio-inspired fabrication has been developed. Accordingly, the mineral phase has been in situ synthesized, calcifying the hydrogel matrix while the latter was crosslinked, finally generating microparticles that can assemble into a bone defect to ensure interconnected pores. Although nano-apatite-biopolymer composites have been widely investigated, microstructural optimization to provide improved distribution and stability of the mineral is rarely achieved. The optimization of the developed method progressively resulted in two types of formulations (15P and 7.5P), with 15 and 7.5 (wt%) phosphate content in the initial precursor. The osteolytic potential was investigated using differentiated macrophages. A commercially available calcium phosphate bone graft substitute (Eurocer 400) was incorporated into the hydrogel, and the obtained composites were in vitro tested for comparison. The cytocompatibility of the microparticles was studied with mouse osteoblast-like cell line MC3T3-E1. Results indicated the best in vitro performance have been obtained for the sample loaded with 7.5P. Preliminary evaluation of biocompatibility into a critical size (3 mm) defect in rabbits showed that 7.5P nanocomposite is associated with newly formed bone in the proximity of the microparticles, after 28 days.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

PubMed

Meng, Jianing; Agrahari, Vivek; Ezoulin, Miezan J; Purohit, Sudhaunshu S; Zhang, Tao; Molteni, Agostino; Dim, Daniel; Oyler, Nathan A; Youan, Bi-Botti C

2017-05-01

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state 31 P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 μm with a drug loading of 7-12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20-50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.

Impact of feed counterion addition and cyclone type on aerodynamic behavior of alginic-atenolol microparticles produced by spray drying.

PubMed

Ceschan, Nazareth Eliana; Bucalá, Verónica; Ramírez-Rigo, María Verónica; Smyth, Hugh David Charles

2016-12-01

The inhalatory route has emerged as an interesting non-invasive alternative for drug delivery. This allows both pulmonary (local) and systemic treatments (via alveolar absorption). Further advantages in terms of stability, dose and patient preference have often lead researchers to focus on dry powder inhaler delivery systems. Atenolol is an antihypertensive drug with low oral bioavailability and gastrointestinal side effects. Because atenolol possesses adequate permeation across human epithelial membranes, it has been proposed as a good candidate for inhalatory administration. In a previous work, atenolol was combined with alginic acid (AA) and microparticles were developed using spray-drying (SD) technology. Different AA/atenolol ratios, total feed solid content and operative variables were previously explored. In order to improve particle quality for inhalatory administration and the SD yield, in this work the AA acid groups not neutralized by atenolol were kept either free or neutralized to pH∼7 and two different SD cyclones were used. Particle morphology, flow properties, moisture uptake and in vitro aerosolization behavior at different pressure drops were studied. When the AA acid groups were neutralized, particle size decreased as a consequence of the lower feed viscosity. The SD yield and in vitro particle deposition significantly increased when a high performance cyclone was employed, and even when lactose carrier particles were not used. Although the in vitro particle deposition decreased when the storage relative humidity increased, the developed SD powders showed adequate characteristics to be administered by inhalatory route up to storage relative humidities of about 60%. Copyright © 2016 Elsevier B.V. All rights reserved.

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

PubMed Central

Vinner, Gurinder K.; Vladisavljević, Goran T.; Clokie, Martha R. J.

2017-01-01

The prevalence of pathogenic bacteria acquiring multidrug antibiotic resistance is a global health threat to mankind. This has motivated a renewed interest in developing alternatives to conventional antibiotics including bacteriophages (viruses) as therapeutic agents. The bacterium Clostridium difficile causes colon infection and is particularly difficult to treat with existing antibiotics; phage therapy may offer a viable alternative. The punitive environment within the gastrointestinal tract can inactivate orally delivered phages. C. difficile specific bacteriophage, myovirus CDKM9 was encapsulated in a pH responsive polymer (Eudragit® S100 with and without alginate) using a flow focussing glass microcapillary device. Highly monodispersed core-shell microparticles containing phages trapped within the particle core were produced by in situ polymer curing using 4-aminobenzoic acid dissolved in the oil phase. The size of the generated microparticles could be precisely controlled in the range 80 μm to 160 μm through design of the microfluidic device geometry and by varying flow rates of the dispersed and continuous phase. In contrast to free ‘naked’ phages, those encapsulated within the microparticles could withstand a 3 h exposure to simulated gastric fluid at pH 2 and then underwent a subsequent pH triggered burst release at pH 7. The significance of our research is in demonstrating that C. difficile specific phage can be formulated and encapsulated in highly uniform pH responsive microparticles using a microfluidic system. The microparticles were shown to afford significant protection to the encapsulated phage upon prolonged exposure to an acid solution mimicking the human stomach environment. Phage encapsulation and subsequent release kinetics revealed that the microparticles prepared using Eudragit® S100 formulations possess pH responsive characteristics with phage release triggered in an intestinal pH range suitable for therapeutic purposes. The results reported here provide proof-of-concept data supporting the suitability of our approach for colon targeted delivery of phages for therapeutic purposes. PMID:29023522

Mucoadhesive hydrogel microparticles based on poly (methacrylic acid-vinyl pyrrolidone)-chitosan for oral drug delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2011-05-01

The study was aimed at the evaluation of N-vinyl pyrrolidone (NVP) incorporated polymethacrylic acid-chitosan microparticles for oral drug delivery applications. Poly (methacrylic acid)-chitosan (PMC) and poly(methacrylic acid-vinyl pyrrolidone)-chitosan (PMVC) microparticles were prepared by an ionic-gelation method. Mucoadhesion behaviour of these particles was evaluated by ex-vivo adhesion method using freshly excised rat intestinal tissue. Cytotoxicity and absorption enhancing property of PMC and PMVC particles were evaluated on Caco 2 cell monolayers. Protease enzyme inhibition capability and insulin loading/release properties of these hydrogel particles was evaluated under in vitro experimental conditions. Addition of NVP units enhanced the mucoadhesion behavior of PMC particles on isolated rat intestinal tissue. Both PMC and PMVC particles were found non-toxic on Caco 2 cell monolayers and PMC particles was more effective in improving paracellular transport of fluorescent dextran across Caco 2 cell monolayers as compared to PMVC particles. However, protease inhibition efficacy of PMC particles was not significantly affected with NVP addition. NVP incorporation improved the insulin release properties of PMC microparticles at acidic pH. Hydrophilic modification seems to be an interesting approach in improving mucoadhesion capability of PMC microparticles.

Alginate-hydroxypropylcellulose hydrogel microbeads for alkaline phosphatase encapsulation.

PubMed

Karewicz, A; Zasada, K; Bielska, D; Douglas, T E L; Jansen, J A; Leeuwenburgh, S C G; Nowakowska, M

2014-01-01

There is a growing interest in using proteins as therapeutics agents. Unfortunately, they suffer from limited stability and bioavailability. We aimed to develop a new delivery system for proteins. ALP, a model protein, was successfully encapsulated in the physically cross-linked sodium alginate/hydroxypropylcellulose (ALG-HPC) hydrogel microparticles. The obtained objects had regular, spherical shape and a diameter of ∼4 µm, as confirmed by optical microscopy and SEM analysis. The properties of the obtained microbeads could be controlled by temperature and additional coating or crosslinking procedures. The slow, sustained release of ALP in its active form with no initial burst effect was observed for chitosan-coated microspheres at pH = 7.4 and 37 °C. Activity of ALP released from ALG/HPC microspheres was confirmed by the occurance of effectively induced mineralization. SEM and AFM images revealed formation of the interpenetrated three-dimensional network of mineral, originating from the microbeads' surfaces. FTIR and XRD analyses confirmed formation of hydroxyapatite.

Retention and release of oil-in-water emulsions from filled hydrogel beads composed of calcium alginate: impact of emulsifier type and pH.

PubMed

Zeeb, Benjamin; Saberi, Amir Hossein; Weiss, Jochen; McClements, David Julian

2015-03-21

Delivery systems based on filled hydrogel particles (microgels) can be fabricated from natural food-grade lipids and biopolymers. The potential for controlling release characteristics by modulating the electrostatic interactions between emulsifier-coated lipid droplets and the biopolymer matrix within hydrogel particles was investigated. A multistage procedure was used to fabricate calcium alginate beads filled with lipid droplets stabilized by non-ionic, cationic, anionic, or zwitterionic emulsifiers. Oil-in-water emulsions stabilized by Tween 60, DTAB, SDS, or whey protein were prepared by microfluidization, mixed with various alginate solutions, and then microgels were formed by simple extrusion into calcium solutions. The microgels were placed into a series of buffer solutions with different pH values (2 to 11). Lipid droplets remained encapsulated under acidic and neutral conditions, but were released under highly basic conditions (pH 11) due to hydrogel swelling when the alginate concentration was sufficiently high. Lipid droplet release increased with decreasing alginate concentration, which could be attributed to an increase in the pore size of the hydrogel matrix. These results have important implications for the design of delivery systems to entrap and control the release of lipophilic bioactive components within filled hydrogel particles.

Physicochemical Characterization of a Heat Treated Calcium Alginate Dry Film Prepared with Chicken Stock.

PubMed

Báez, Germán D; Piccirilli, Gisela N; Ballerini, Griselda A; Frattini, Agustín; Busti, Pablo A; Verdini, Roxana A; Delorenzi, Néstor J

2017-04-01

Solid sodium alginate was dissolved into chicken stock in order to give a final alginate concentration of 0.9 percent (w/v). Calcium ions present in chicken stock were enough to induce ionic gelation. After drying, Fourier transform infrared spectroscopy, thickness and mechanical properties of films obtained were determined. Calcium alginate-chicken stock films were heated at 130 °C for different times between 0 and 15 min. Mechanical and optical studies, differential scanning calorimetry, visual aspect and scanning electron microscopy were carried out to describe physicochemical properties of heat treated films. Heating developed a maroon ochre color and increased the brittleness (crispness) of the films related to the intensity of the treatment. Differential scanning thermometry and study on appearance of the films suggested that Maillard reactions may be responsible for the observed changes. Maillard reactions mainly occurred between reducing sugar monomers and free amino groups of gelatin peptides present in the chicken stock, and between alginate and gelatin peptides to a lesser extent. In addition, the plasticizing effect of fat added with chicken stock was also studied. These studies suggest a potential use of heat treated chicken stock films as a substitute of roasted chicken skin. © 2017 Institute of Food Technologists®.

Influence of internal composition on physicochemical properties of alginate aqueous-core capsules.

PubMed

Ben Messaoud, Ghazi; Sánchez-González, Laura; Probst, Laurent; Desobry, Stéphane

2016-05-01

To enhance physicochemical properties of alginate aqueous-core capsules, conventional strategies were focused in literature on designing composite and coated capsules. In the present study, own effect of liquid-core composition on mechanical and release properties was investigated. Capsules were prepared by dripping a CaCl2 solution into an alginate gelling solution. Viscosity of CaCl2 solution was adjusted by adding cationic, anionic and non-ionic naturally derived polymers, respectively chitosan, xanthan gum and guar gum. In parallel, uniform alginate hydrogels were prepared by different methods (pouring, in situ forming and mixing). Mechanical stability of capsules and plane hydrogels were respectively evaluated by compression experiments and small amplitude oscillatory shear rheology and then correlated. Capsules permeability was evaluated by monitoring diffusion of encapsulated cochineal dye, riboflavin and BSA. The core-shell interactions were investigated by ATR-FTIR. Results showed that inner polymer had an impact on membrane stability and could act as an internal coating or provide mechanical reinforcement. Mechanical properties of alginate capsules were in a good agreement with rheological behavior of plane hydrogels. Release behavior of the entrapped molecules changed considerably. This study demonstrated the importance of aqueous-core composition, and gave new insights for possible adjusting of microcapsules physicochemical properties by modulating core-shell interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation.

PubMed

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-09-01

The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs.

Furosemide Loaded Silica-Lipid Hybrid Microparticles: Formulation Development, in vitro and ex vivo Evaluation

PubMed Central

Sambaraj, Swapna; Ammula, Divya; Nagabandi, Vijaykumar

2015-01-01

Purpose: The main objective of the current research work was to formulate and evaluate furosemide loaded silica lipid hybrid microparticles for improved oral delivery. A novel silica-lipid hybrid microparticulate system is used for enhancing the oral absorption of low solubility and low permeability of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug solubilising effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilisation, which leads to enhanced oral bioavailability. Methods: The slica lipid hybrid (SLH) microparticles were composed of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80) and adsorbent (Aerosol 380). Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. Results: In vitro dissolution studies conducted under simulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for SLH microparticles compared to that of pure drug (furosemide) and marketed formulation Lasix®. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by X-ray powder diffraction and Fourier transform infrared spectroscopic analysis confirmed non-crystalline nature and more compatibility of furosemide in silica-lipid hybrid microparticles. Conclusion: It can be concluded that the role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. PMID:26504763

Self-Healable and Cold-Resistant Supercapacitor Based on a Multifunctional Hydrogel Electrolyte.

PubMed

Tao, Feng; Qin, Liming; Wang, Zhikui; Pan, Qinmin

2017-05-10

Excellent self-healability and cold resistance are attractive properties for a portable/wearable energy-storage device. However, achieving the features is fundamentally dependent on an intrinsically self-healable electrolyte with high ionic conduction at low temperature. Here we report such a hydrogel electrolyte comprising sodium alginate cross-linked by dynamic catechol-borate ester bonding. Since its dynamically cross-linked alginate network can tolerate high-content inorganic salts, the electrolyte possesses excellent healing efficiency/cyclability but also high ionic conduction at both room temperature and low temperature. A supercapacitor with the multifunctional hydrogel electrolyte completely restores its capacitive properties even after breaking/healing for 10 cycles without external stimulus. At a low temperature of -10 °C, the capacitor is even able to maintain at least 80% of its room-temperature capacitance. Our investigations offer a strategy to assemble self-healable and cold-resistant energy storage devices by using a multifunctional hydrogel electrolyte with rationally designed polymeric networks, which has potential application in portable/wearable electronics, intelligent apparel or flexible robot, and so on.

Development and Evaluation of Chitosan Microparticles Based Dry Powder Inhalation Formulations of Rifampicin and Rifabutin.

PubMed

Pai, Rohan V; Jain, Rajesh R; Bannalikar, Anilkumar S; Menon, Mala D

2016-04-01

The lung is the primary entry site and target for Mycobacterium tuberculosis; more than 80% of the cases reported worldwide are of pulmonary tuberculosis. Hence, direct delivery of anti-tubercular drugs to the lung would be beneficial in reducing both, the dose required, as well as the duration of therapy for pulmonary tuberculosis. In the present study, microsphere-based dry powder inhalation systems of the anti-tubercular drugs, rifampicin and rifabutin, were developed and evaluated, with a view to achieve localized and targeted delivery of these drugs to the lung. The drug-loaded chitosan microparticles were prepared by an ionic gelation method, followed by spray-drying to obtain respirable particles. The microparticles were evaluated for particle size and drug release. The drug-loaded microparticles were then adsorbed onto an inhalable lactose carrier and characterized for in vitro lung deposition on an Andersen Cascade Impactor (ACI) followed by in vitro uptake study in U937 human macrophage cell lines. In vivo toxicity of the developed formulations was evaluated using Sprague Dawley rats. Both rifampicin and rifabutin-loaded microparticles had MMAD close to 5 μm and FPF values of 21.46% and 29.97%, respectively. In vitro release study in simulated lung fluid pH 7.4 showed sustained release for 12 hours for rifampicin microparticles and up to 96 hours for rifabutin microparticles, the release being dependent on both swelling of the polymer and solubility of the drugs in the dissolution medium. In vitro uptake studies in U937 human macrophage cell line suggested that microparticles were internalized within the macrophages. In vivo acute toxicity study of the microparticles in Sprague Dawley rats revealed no significant evidence for local adverse effects. Thus, spray-dried microparticles of the anti-tubercular drugs, rifampicin and rifabutin, could prove to be an improved, targeted, and efficient system for treatment of tuberculosis.

Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

PubMed

Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

2008-02-28

The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.

Core-shell hydrogel beads with extracellular matrix for tumor spheroid formation.

PubMed

Yu, L; Grist, S M; Nasseri, S S; Cheng, E; Hwang, Y-C E; Ni, C; Cheung, K C

2015-03-01

Creating multicellular tumor spheroids is critical for characterizing anticancer treatments since they may provide a better model of the tumor than conventional monolayer culture. Moreover, tumor cell interaction with the extracellular matrix can determine cell organization and behavior. In this work, a microfluidic system was used to form cell-laden core-shell beads which incorporate elements of the extracellular matrix and support the formation of multicellular spheroids. The bead core (comprising a mixture of alginate, collagen, and reconstituted basement membrane, with gelation by temperature control) and shell (comprising alginate hydrogel, with gelation by ionic crosslinking) were simultaneously formed through flow focusing using a cooled flow path into the microfluidic chip. During droplet gelation, the alginate acts as a fast-gelling shell which aids in preventing droplet coalescence and in maintaining spherical droplet geometry during the slower gelation of the collagen and reconstituted basement membrane components as the beads warm up. After droplet gelation, the encapsulated MCF-7 cells proliferated to form uniform spheroids when the beads contained all three components: alginate, collagen, and reconstituted basement membrane. The dose-dependent response of the MCF-7 cell tumor spheroids to two anticancer drugs, docetaxel and tamoxifen, was compared to conventional monolayer culture.

Injectable alginate-O-carboxymethyl chitosan/nano fibrin composite hydrogels for adipose tissue engineering.

PubMed

Jaikumar, Dhanya; Sajesh, K M; Soumya, S; Nimal, T R; Chennazhi, K P; Nair, Shantikumar V; Jayakumar, R

2015-03-01

Injectable, biodegradable scaffolds are required for soft tissue reconstruction owing to its minimally invasive approach. Such a scaffold can mimic the native extracellular matrix (ECM), provide uniform distribution of cells and overcome limitations like donor site morbidity, volume loss, etc. So, here we report two classes of biocompatible and biodegradable hydrogel blend systems namely, Alginate/O-carboxymethyl chitosan (O-CMC) and Alginate/poly (vinyl alcohol) (PVA) with the inclusion of fibrin nanoparticles in each. The hydrogels were prepared by ionic cross-linking method. The developed hydrogels were compared in terms of its swelling ratio, degradation profile, compressive strength and elastic moduli. From these preliminary findings, it was concluded that Alginate/O-CMC formed a better blend for tissue engineering applications. The potential of the formed hydrogel as an injectable scaffold was revealed by the survival of adipose derived stem cells (ADSCs) on the scaffold by its adhesion, proliferation and differentiation into adipocytes. Cell differentiation studies of fibrin incorporated hydrogel scaffolds showed better differentiation was confirmed by Oil Red O staining technique. These injectable gels have potential in soft tissue regeneration. Copyright © 2014 Elsevier B.V. All rights reserved.

Polyelectrolyte Complex Inclusive Biohybrid Microgels for Tailoring Delivery of Copigmented Anthocyanins.

PubMed

Tan, Chen; B Celli, Giovana; Lee, Michelle; Licker, Jonathan; Abbaspourrad, Alireza

2018-05-14

This study fabricated a novel biohybrid microgel containing polysaccharide-based polyelectrolyte complexes (PECs) for anthocyanins. Herein, anthocyanins were encapsulated into PECs composed of chondroitin sulfate and chitosan, followed by incorporation into alginate microgels using emulsification/internal gelation method. We demonstrated that PECs incorporation strongly affected the properties of microgels, dependent on the polysaccharide concentration and pH in which they were fabricated. The dense internal network surrounded by an alginate shell was clearly visualized in cross-sectioned PECs-microgels. Stability studies carried out under varying ionic strength and pH conditions demonstrated the stimuli-responsiveness of the PECs-microgels. Additionally, the presence of PECs conferred microgels with high rigidity during freeze-drying and excellent reconstitution capacity upon rehydration. These observations were attributed to the modulation of electrostatic and hydrogen-bonding cross-linking between PECs and the alginate gel matrix and suggest the PECs inclusive microgels hold promise as delivery vehicles for the controlled release of hydrophilic bioactive compounds.

Large strain deformation behavior of polymeric gels in shear- and cavitation rheology

NASA Astrophysics Data System (ADS)

Hashemnejad, Seyed Meysam; Kundu, Santanu

Polymeric gels are used in many applications including in biomedical and in food industries. Investigation of mechanical responses of swollen polymer gels and linking that to the polymer chain dynamics are of significant interest. Here, large strain deformation behavior of two different gel systems and with different network architecture will be presented. We consider biologically relevant polysaccharide hydrogels, formed through ionic and covalent crosslinking, and physically associating triblock copolymer gels in a midblock selective solvent. Gels with similar low-strain shear modulus display distinctly different non-linear rheological behavior in large strain shear deformation. Both these gels display strain-stiffening behavior in shear-deformation prior to macroscopic fracture of the network, however, only the alginate gels display negative normal stress. The cavitation rheology data show that the critical pressure for cavitation is higher for alginate gels than that observed for triblock gels. These distinctly different large-strain deformation behavior has been related to the gel network structure, as alginate chains are much stiffer than the triblock polymer chains.

Alginate beads containing water treatment residuals for arsenic removal from water-formation and adsorption studies.

PubMed

Ociński, Daniel; Jacukowicz-Sobala, Irena; Kociołek-Balawejder, Elżbieta

2016-12-01

Water treatment residuals (WTRs) produced in large quantities during deironing and demanganization of infiltration water, due to high content of iron and manganese oxides, exhibit excellent sorptive properties toward arsenate and arsenite. Nonetheless, since they consist of microparticles, their practical use as an adsorbent is limited by difficulties with separation from treated solutions. The aim of this study was entrapment of chemically pretreated WTR into calcium alginate polymer and examination of sorptive properties of the obtained composite sorbent toward As(III) and As(V). Different products were formed varying in WTR content as well as in density of alginate matrix. In order to determine the key parameters of the adsorption process, both equilibrium and kinetic studies were conducted. The best properties were exhibited by a sorbent containing 5 % residuals, formed in alginate solution with a concentration of 1 %. In slightly acidic conditions (pH 4.5), its maximum sorption capacity was 3.4 and 2.9 mg g -1 for As(III) and As(V), respectively. At neutral pH, the adsorption effectiveness decreased to 3.3 mg As g -1 for arsenites and to 0.7 mg As g -1 for arsenates. The presence of carboxylic groups in polymer chains impeded in neutral conditions the diffusion of anions into sorbent beads; therefore, the main rate-limiting step of the adsorption, mainly in the case of arsenates, was intraparticle diffusion. The optimal condition for simultaneous removal of arsenates and arsenites from water by means of the obtained composite sorbent is slightly acidic pH, ensuring similar adsorption effectiveness for both arsenic species.

A synbiotic multiparticulate microcapsule for enhancing inulin intestinal release and Bifidobacterium gastro-intestinal survivability.

PubMed

Fayed, Bahgat; Abood, Amira; El-Sayed, Hoda S; Hashem, Amal M; Mehanna, Nayra S H

2018-08-01

A novel synbiotic multiparticulate microparticle was produced in the current study to expand the synbiotic industrial applications. Initially, the inulin was fabricated into PLGA nanoparticles. After the inulin entrapment efficiency was boosted to reach 92.9 ± 8.4% by adjusting the formulation parameters, the developed particles were characterized by different techniques such as particle size analyzer, TEM, and TLC. The obtained data showed that the particle size was 115.8 ± 82.7 nm, the particles had smooth surface and round shape, and the fabrication procedure did not affect the integrity of the inulin. Later, the inulin loaded nanoparticles together with selected Bifidobacterium species were double coated with gum arabic and alginate. The maximum survivability of the encapsulated Bifidobacterium in the simulated gastric solution reached 88.29% of the initial population, which was significantly higher than the survivability of the free bacteria. Finally, the inulin release from the multiparticulate microparticles was studied and found to be sustained over three days. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chitosan-based water-propelled micromotors with strong antibacterial activity.

PubMed

Delezuk, Jorge A M; Ramírez-Herrera, Doris E; Esteban-Fernández de Ávila, Berta; Wang, Joseph

2017-02-09

A rapid and efficient micromotor-based bacteria killing strategy is described. The new antibacterial approach couples the attractive antibacterial properties of chitosan with the efficient water-powered propulsion of magnesium (Mg) micromotors. These Janus micromotors consist of Mg microparticles coated with the biodegradable and biocompatible polymers poly(lactic-co-glycolic acid) (PLGA), alginate (Alg) and chitosan (Chi), with the latter responsible for the antibacterial properties of the micromotor. The distinct speed and efficiency advantages of the new micromotor-based environmentally friendly antibacterial approach have been demonstrated in various control experiments by treating drinking water contaminated with model Escherichia coli (E. coli) bacteria. The new dynamic antibacterial strategy offers dramatic improvements in the antibacterial efficiency, compared to static chitosan-coated microparticles (e.g., 27-fold enhancement), with a 96% killing efficiency within 10 min. Potential real-life applications of these chitosan-based micromotors for environmental remediation have been demonstrated by the efficient treatment of seawater and fresh water samples contaminated with unknown bacteria. Coupling the efficient water-driven propulsion of such biodegradable and biocompatible micromotors with the antibacterial properties of chitosan holds great considerable promise for advanced antimicrobial water treatment operation.

Stabilization of model beverage cloud emulsions using protein-polysaccharide electrostatic complexes formed at the oil-water interface.

PubMed

Harnsilawat, Thepkunya; Pongsawatmanit, Rungnaphar; McClements, David J

2006-07-26

The potential of utilizing interfacial complexes, formed through the electrostatic interactions of proteins and polysaccharides at oil-water interfaces, to stabilize model beverage cloud emulsions has been examined. These interfacial complexes were formed by mixing charged polysaccharides with oil-in-water emulsions containing oppositely charged protein-coated oil droplets. Model beverage emulsions were prepared that consisted of 0.1 wt % corn oil droplets coated by beta-lactoglobulin (beta-Lg), beta-Lg/alginate, beta-Lg/iota-carrageenan, or beta-Lg/gum arabic interfacial layers (pH 3 or 4). Stable emulsions were formed when the polysaccharide concentration was sufficient to saturate the protein-coated droplets. The emulsions were subjected to variations in pH (from 3 to 7), ionic strength (from 0 to 250 mM NaCl), and thermal processing (from 30 or 90 degrees C), and the influence on their stability was determined. The emulsions containing alginate and carrageenan had the best stability to ionic strength and thermal processing. This study shows that the controlled formation of protein-polysaccharide complexes at droplet surfaces may be used to produce stable beverage emulsions, which may have important implications for industrial applications.

Calcium alginate particles for the combined delivery of platelet lysate and vancomycin hydrochloride in chronic skin ulcers.

PubMed

Mori, Michela; Rossi, Silvia; Bonferoni, Maria Cristina; Ferrari, Franca; Sandri, Giuseppina; Riva, Federica; Del Fante, Claudia; Perotti, Cesare; Caramella, Carla

2014-01-30

The aim of the present work was the development of a powder formulation for the combined delivery of platelet lysate and of a model antibiotic drug, vancomycin hydrochloride (VCM), in chronic skin ulcers. Calcium alginate particles were prepared by freeze-drying beads obtained by ionic gelation method. The experimental conditions adopted permitted the complete loading of VCM and of PDGF AB, the growth factor chosen as representative of those contained in PL. Such particles where able to absorb PBS (mimicking wound exudate), to form a gel and to modulate the release of VCM and of PDGF AB. They are characterized by enhancement properties of human fibroblast proliferation due to PL presence. In particular, PL, when loaded in alginate particles, was able not only to increase the number of viable cells, but also the number of cells in proliferative phase. Such properties were comparable to those of fresh PL indicating the capability of calcium alginate particles to load PL bioactive substances without altering their activity. The formulation developed is characterized by an easier and a less painful administration with respect to traditional gauzes and semisolid preparations and permits the loading in the same dosage form of active substances of different nature avoiding eventual incompatibility problems. Copyright © 2013 Elsevier B.V. All rights reserved.

Electrically responsive materials based on polycarbazole/sodium alginate hydrogel blend for soft and flexible actuator application.

PubMed

Sangwan, Watchara; Petcharoen, Karat; Paradee, Nophawan; Lerdwijitjarud, Wanchai; Sirivat, Anuvat

2016-10-20

The electromechanical properties, namely the storage modulus sensitivity and bending, of sodium alginate (SA) hydrogels and polycarbazole/sodium alginate (PCB/SA) hydrogel blends under applied electric field was investigated. The electromechanical properties of the pristine SA were studied under effects of crosslinking types and SA molecular weights, whereas the PCB/SA hydrogel blends were studied under the effect of PCB concentrations. The storage modulus sensitivity and bending of the pristine SA as crosslinked by the ionic crosslinking agent were found to be higher than those of the covalent crosslinking. The storage modulus sensitivity and deflection of the SA increased monotonically with increasing molecular weight. The highest electromechanical response of the PCB/SA hydrogel blends was obtained from the blend with 0.10% v/v PCB as it provided surprisingly the highest ever storage modulus sensitivity, (G'-G'0)/G'0 where G'0 and G' are the storage modulus without and with applied electric field, respectively, at 18.5 under applied electric field strength of 800V/mm. Copyright © 2016 Elsevier Ltd. All rights reserved.

Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery.

PubMed

Sajeesh, S; Bouchemal, K; Sharma, C P; Vauthier, C

2010-02-01

Aim of the present work was to develop novel thiol-functionalized hydrogel microparticles based on poly(methacrylic acid)-chitosan-poly(ethylene glycol) (PCP) for oral drug delivery applications. PCP microparticles were prepared by a modified ionic gelation process in aqueous medium. Thiol modification of surface carboxylic acid groups of PCP micro particles was carried out by coupling l-cysteine with a water-soluble carbodiimide. Ellman's method was adopted to quantify the sulfhydryl groups, and dynamic light-scattering technique was used to measure the average particle size. Cytotoxicity of the modified particles was evaluated on Caco 2 cells by MTT assay. Effect of thiol modification on permeability of paracellular marker fluorescence dextran (FD4) was evaluated on Caco 2 cell monolayers and freshly excised rat intestinal tissue with an Ussing chamber set-up. Mucoadhesion experiments were carried out by an ex vivo bioadhesion method with excised rat intestinal tissue. The average size of the PCP microparticles was increased after thiol modification. Thiolated microparticles significantly improved the paracellular permeability of FD4 across Caco 2 cell monolayers, with no sign of toxicity. However, the efficacy of thiolated system remained low when permeation experiments were carried out across excised intestinal membrane. This was attributed to the high adhesion of the thiolated particles on the gut mucosa. Nevertheless, it can be concluded that surface thiolation is an interesting strategy to improve paracellular permeability of hydrophilic macromolecules. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment.

PubMed

Pinto Reis, Catarina; Vasques Roque, Luís; Baptista, Marina; Rijo, Patrícia

2016-01-01

Oral candidiasis is a mycosis on the mucous membranes of the mouth but not limited to the mouth. Nystatin is one of the most frequently employed antifungal agents to treat infections and may be safely given orally as well as applied topically but its absorption through mucocutaneous membranes such as the gut and the skin is minimal. The purpose of this study is to enhance the effectiveness of nystatin using particulate system such as beads, micro- and nanoparticles of alginate incorporated into toothpaste. Those particulate systems of nystatin were prepared by extrusion/external gelation for beads and emulsification/internal gelation for micro- and nanoparticles and characterized. Small, anionic charged and monodispersed particles were successfully produced. The type of particulate system influenced all previous parameters, being microparticles the most suitable particulate system of nystatin showing the slowest release, the highest inhibitory effect of Candida albicans over a period of one year. Those results allowed the conclusion that alginate exhibits properties that enable the in vitro functionality of encapsulated nystatin and thus may provide the basis for new successful approaches for the treatment of oral antifungal infections such as oral candidiasis.

Polypyrrole/Alginate Hybrid Hydrogels: Electrically Conductive and Soft Biomaterials for Human Mesenchymal Stem Cell Culture and Potential Neural Tissue Engineering Applications.

PubMed

Yang, Sumi; Jang, LindyK; Kim, Semin; Yang, Jongcheol; Yang, Kisuk; Cho, Seung-Woo; Lee, Jae Young

2016-11-01

Electrically conductive biomaterials that can efficiently deliver electrical signals to cells or improve electrical communication among cells have received considerable attention for potential tissue engineering applications. Conductive hydrogels are desirable particularly for neural applications, as they can provide electrical signals and soft microenvironments that can mimic native nerve tissues. In this study, conductive and soft polypyrrole/alginate (PPy/Alg) hydrogels are developed by chemically polymerizing PPy within ionically cross-linked alginate hydrogel networks. The synthesized hydrogels exhibit a Young's modulus of 20-200 kPa. Electrical conductance of the PPy/Alg hydrogels could be enhanced by more than one order of magnitude compared to that of pristine alginate hydrogels. In vitro studies with human bone marrow-derived mesenchymal stem cells (hMSCs) reveal that cell adhesion and growth are promoted on the PPy/Alg hydrogels. Additionally, the PPy/Alg hydrogels support and greatly enhance the expression of neural differentiation markers (i.e., Tuj1 and MAP2) of hMSCs compared to tissue culture plate controls. Subcutaneous implantation of the hydrogels for eight weeks induces mild inflammatory reactions. These soft and conductive hydrogels will serve as a useful platform to study the effects of electrical and mechanical signals on stem cells and/or neural cells and to develop multifunctional neural tissue engineering scaffolds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Semipermeable Capsules Wrapping a Multifunctional and Self-regulated Co-culture Microenvironment for Osteogenic Differentiation

NASA Astrophysics Data System (ADS)

Correia, Clara R.; Pirraco, Rogério P.; Cerqueira, Mariana T.; Marques, Alexandra P.; Reis, Rui L.; Mano, João F.

2016-02-01

A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the “stem cell niche”, the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources.

Doped hydrophobic silica nano- and micro-particles as novel agents for developing latent fingerprints.

PubMed

Theaker, Brenden J; Hudson, Katherine E; Rowell, Frederick J

2008-01-15

Novel hydrophobic silica based particles have been developed to visualise latent fingerprints. The composition of the particles has been designed to maximise both hydrophobic and ionic interactions between a variety of coloured and fluorescent reporter molecules and the silicate backbone within the particles. The resulting doped particles retain the incorporated dyes with high affinity. In addition, a variety of sub-particles have also been embedded to again produce coloured or magnetisable hydrophobic particles. The particles can be harvested as nanoparticles or microparticles. The former are applied to latent fingerprints as an aqueous suspension and the latter as a dusting agent using brushes or a magnetic wand. Examples of the prints produced using these agents are given. The resulting prints have good definition.

Microencapsulation of bioactive principles with an airless spray-gun suitable for processing high viscous solutions.

PubMed

Cocchietto, Moreno; Blasi, Paolo; Lapasin, Romano; Moro, Chiara; Gallo, Davide; Sava, Gianni

2013-11-19

to design, assemble and test a prototype of a novel production plant, suitable for producing microparticles (MPs) by processing highly viscous feed solutions (FSs). the prototype has been built using a commercial air compressor, a piston pump, an airless spray-gun, a customized air-treatment section, a timer, a rotating base, and a filtration section. Preliminary prototype parameter setting was carried out to individuate the best performing nozzle's dimension, the nebulization timing, and the CaCl2 concentration in the gelation fluid. In addition, prototype throughput (1 L to 5 L) and the range of practicable feed solution (FS) viscosities were assayed. A set of four batches was prepared in order to characterize the MPs, in terms of mean particle size and distribution, flow properties, swelling, encapsulation efficiency and release. according to a qualitative scoring, the large nozzle was suitable to nebulize FSs at a higher alginate concentration. Conversely, the small nozzle performed better in the processing of FSs with an alginate concentration up to 2% w/v. Only at the highest degree of viscosity, corresponding to 5% w/v of alginate, the FS processing was not technically possible. Among the CaCl2 concentrations considered, 15% w/v was recognized as the most versatile. The prototype appears to be convenient and suitable to grant a high yield starting from 2 L of FS. The flow behavior of the FSs assayed can be satisfactorily described with the Carreau-Yasuda equation and the throughput begins to slightly decrease for FSs at alginate concentrations exceeding 3% w/v. MP morphology was irregular with crumpled shape. The angle of repose indicates a good flowability and the release studies showed gastro-resistance and potential prolonged release applications. the novel prototype of production plant is suitable to process large amounts (2 L or more) of FSs, characterized by a high viscosity, to produce MPs suitable for bioactive principle delivery.

Microencapsulation of Bioactive Principles with an Airless Spray-Gun Suitable for Processing High Viscous Solutions

PubMed Central

Cocchietto, Moreno; Blasi, Paolo; Lapasin, Romano; Moro, Chiara; Gallo, Davide; Sava, Gianni

2013-01-01

Purpose: to design, assemble and test a prototype of a novel production plant, suitable for producing microparticles (MPs) by processing highly viscous feed solutions (FSs). Methods: the prototype has been built using a commercial air compressor, a piston pump, an airless spray-gun, a customized air-treatment section, a timer, a rotating base, and a filtration section. Preliminary prototype parameter setting was carried out to individuate the best performing nozzle’s dimension, the nebulization timing, and the CaCl2 concentration in the gelation fluid. In addition, prototype throughput (1 L to 5 L) and the range of practicable feed solution (FS) viscosities were assayed. A set of four batches was prepared in order to characterize the MPs, in terms of mean particle size and distribution, flow properties, swelling, encapsulation efficiency and release. Results: according to a qualitative scoring, the large nozzle was suitable to nebulize FSs at a higher alginate concentration. Conversely, the small nozzle performed better in the processing of FSs with an alginate concentration up to 2% w/v. Only at the highest degree of viscosity, corresponding to 5% w/v of alginate, the FS processing was not technically possible. Among the CaCl2 concentrations considered, 15% w/v was recognized as the most versatile. The prototype appears to be convenient and suitable to grant a high yield starting from 2 L of FS. The flow behavior of the FSs assayed can be satisfactorily described with the Carreau-Yasuda equation and the throughput begins to slightly decrease for FSs at alginate concentrations exceeding 3% w/v. MP morphology was irregular with crumpled shape. The angle of repose indicates a good flowability and the release studies showed gastro-resistance and potential prolonged release applications. Conclusions: the novel prototype of production plant is suitable to process large amounts (2 L or more) of FSs, characterized by a high viscosity, to produce MPs suitable for bioactive principle delivery. PMID:24956192

Nanoparticle-in-microparticle oral drug delivery system of a clinically relevant darunavir/ritonavir antiretroviral combination.

PubMed

Augustine, Robin; Ashkenazi, Dana Levin; Arzi, Roni Sverdlov; Zlobin, Vita; Shofti, Rona; Sosnik, Alejandro

2018-05-01

Nanonizationhas been extensively investigated to increase theoral bioavailability of hydrophobicdrugsin general andantiretrovirals(ARVs)used inthe therapy of the human immunodeficiency virus (HIV) infection in particular. Weanticipatedthatin the caseofprotease inhibitors, a family of pH-dependent ARVsthatdisplay high aqueous solubility undertheacidconditionsof thestomach andextremely low solubilityunder the neutral ones ofthe small intestine, this strategy might failowing to an uncontrolled dissolution-re-precipitation process that will take place along the gastrointestinal tract.To tackle thisbiopharmaceutical challenge, in this work, wedesigned, produced and fully characterized a novelNanoparticle-in-MicroparticleDelivery System(NiMDS)comprised of pure nanoparticlesofthefirst-line protease inhibitor darunavir(DRV) and itsboosting agentritonavir (RIT) encapsulated within film-coated microparticles.For this, a clinically relevant combination of pure DRV and RIT nanoparticles wassynthesized by a sequential nanoprecipitation/solvent diffusion and evaporation method employing sodium alginateas viscosity stabilizer. Then, pure nanoparticles were encapsulated within calcium alginate/chitosanmicroparticlesthat were film-coated with a series ofpoly(methacrylate) copolymers with differential solubility in the gastrointestinal tract. This coating ensured full stability under gastric-like pH and sustained drug release under intestinal one. PharmacokineticstudiesconductedinalbinoSpragueDawleyratsshowed that DRV/RIT-loadedNiMDSs containing 17% w/w drug loading based on dry weight significantlyincreasedthe oral bioavailabilityof DRVby 2.3-foldwith respect to both theunprocessedandthenanonized DRV/RIT combinations that showed statistically similar performance. Moreover, they highlighted the limited advantage of only drugnanonizationto improve the oral pharmacokinetics of protease inhibitors and the potential of our novel delivery approach to improve the oral pharmacokinetics of nanonized poorly water-soluble drugs displaying pH-dependent solubility. Protease inhibitors (PIs) are gold-standard drugs in many ARV cocktails. Darunavir (DRV) is the latest approved PI and it is included in the 20th WHO Model List of Essential Medicines. PIs poorly-water soluble at intestinal pH and more soluble under gastric conditions. Drug nanonization represents one of the most common nanotechnology strategies to increase dissolution rate of hydrophobic drugs and thus, their oral bioavailability. For instance, pure drug nanosuspensions became the most clinically relevant nanoformulation. However, according to the physicochemical properties of PIs, nanonization does not appear as a very beneficial strategy due to the fast dissolution rate anticipated under the acid conditions of the stomach and their uncontrolled recrystallization and precipitation in the small intestine that might result in the formation of particles of unpredictable size and structure (e.g., crystallinity and polymorphism) and consequently, unknown dissolution rate and bioavailability. In this work, we developed a sequential nanoprecipitation method for the production of pure nanoparticles of DRV and its boosting agent ritonavir in a clinically relevant 8:1 wt ratio using alginate as viscosity stabilizer and used this nanosuspension to produce a novel kind of nanoparticle-in-microparticle delivery system that was fully characterized and the pharmacokinetics assessed in rats. The most significant points of the current manuscript are. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Time of flight mass spectra of ions in plasmas produced by hypervelocity impacts of organic and mineralogical microparticles on a cosmic dust analyser

NASA Astrophysics Data System (ADS)

Goldsworthy, B. J.; Burchell, M. J.; Cole, M. J.; Armes, S. P.; Khan, M. A.; Lascelles, S. F.; Green, S. F.; McDonnell, J. A. M.; Srama, R.; Bigger, S. W.

2003-10-01

The ionic plasma produced by a hypervelocity particle impact can be analysed to determine compositional information for the original particle by using a time-of-flight mass spectrometer. Such methods have been adopted on interplanetary dust detectors to perform in-situ analyses of encountered grains, for example, the Cassini Cosmic Dust Analyser (CDA). In order to more fully understand the data returned by such instruments, it is necessary to study their response to impacts in the laboratory. Accordingly, data are shown here for the mass spectra of ionic plasmas, produced through the acceleration of microparticles via a 2 MV van de Graaff accelerator and their impact on a dimensionally correct CDA model with a rhodium target. The microparticle dusts examined have three different chemical compositions: metal (iron), organic (polypyrrole and polystyrene latex) and mineral (aluminosilicate clay). These microparticles have mean diameters in the range 0.1 to 1.6 mu m and their velocities range from 1-50 km s-1. They thus cover a wide range of compositions, sizes and speeds expected for dust particles encountered by spacecraft in the Solar System. The advent of new low-density, microparticles with highly controllable attributes (composition, size) has enabled a number of new investigations in this area. The key is the use of a conducting polymer, either as the particle itself or as a thin overlayer on organic (or inorganic) core particles. This conductive coating permits efficient electrostatic charging and acceleration. Here, we examine how the projectile's chemical composition influences the ionic plasma produced after the hypervelocity impact. This study thus extends our understanding of impact plasma formation and detection. The ionization yield normalized to particle mass was found to depend on impact speed to the power (3.4 +/- 0.1) for iron and (2.9 +/- 0.1) for polypyrrole coated polystyrene and aluminosilicate clay. The ioization signal rise time was found to fall for all projectile materials from a few microseconds at low impact speeds (3 km s-1) to a few tenths of a microsecond at higher speeds (approximately 16 km s-1 for aluminosilicate particles and approximately 28 km s-1 for iron and polystyrene particles). At speeds greater than these the rise time was a constant few tenths of a microsecond independent of impact speed. The mass resolution of the time of flight spectrometer was found to be non-linear at high masses above 100 amu. It was Delta m/m = 5 for m = 1 amu and 40 for m = 200 amu. However, although at high masses most mass peaks had the resolution quoted, there were also occasional much narrower mass peaks observed, suggesting that at 250 to 280 amu Delta m/m = 80 to 100. The lower resolutions may be due to closely spaced mass peak signals effectively merging into one observed peak due to the (greater but still finite) resolution found for the isolated mass peaks. Complex mass spectra have been reproducibly obtained from a number of different projectiles that display many charged molecular fragments with masses up to 250 amu and with periodicities of 12-14 amu. These new studies reveal an extremely strong dependence of the time-of-flight mass spectra on the impact speed, particularly at low velocities (1-20 km s-1). In some impact velocity regimes it is possible to distinguish time-of-flight spectra originating from organic microparticles from those obtained from iron microparticles. However, such discrimination was not possible at high impact speeds, nor was it possible to distinguish between the time-of-flight spectra obtained for aluminosilicate particles from those obtained for iron projectiles.

Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2).

PubMed

Kenley, R; Marden, L; Turek, T; Jin, L; Ron, E; Hollinger, J O

1994-10-01

In the current investigation, we report osseous regeneration in critical-size rat calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) and novel delivery systems based on biomaterials. The novel systems combine rhBMP-2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste. The biopolymers tested include autologous blood clot, hydroxypropyl methylcellulose, and sodium alginate cross-linked with calcium ion. Insoluble collageneous bone matrix was also studied as a control. Test articles were made at 0-, 10-, and 30-micrograms doses of rhBMP-2 and imiplanted in 8-mm-diameter rat calvarial defects (which will not heal if left untreated). The animals were examined 21 days after implantation by radiography, radiomorphometry, histology, and histomorphometry. All tested materials containing rhBMP-2 restored radiopacity and normal contouring to the calvarial defects. Samples without added rhBMP-2 yielded only soft tissue within the defects. Histology showed restoration of inner and outer bone tables plus marrow constituents. The PLGA microparticles were significantly resorbed at the 21-day time point. Although small differences between delivery systems were evident at 0- and 10-micrograms rhBMP-2 doses, all test articles performed essentially equivalently at the 30-micrograms dose. Thus, novel delivery systems for rhBMP-2 offer the promise of combining the intrinsic bioactivity of the osteoinductive protein with pharmaceutically acceptable biomaterials.

A large deformation viscoelastic model for double-network hydrogels

NASA Astrophysics Data System (ADS)

Mao, Yunwei; Lin, Shaoting; Zhao, Xuanhe; Anand, Lallit

2017-03-01

We present a large deformation viscoelasticity model for recently synthesized double network hydrogels which consist of a covalently-crosslinked polyacrylamide network with long chains, and an ionically-crosslinked alginate network with short chains. Such double-network gels are highly stretchable and at the same time tough, because when stretched the crosslinks in the ionically-crosslinked alginate network rupture which results in distributed internal microdamage which dissipates a substantial amount of energy, while the configurational entropy of the covalently-crosslinked polyacrylamide network allows the gel to return to its original configuration after deformation. In addition to the large hysteresis during loading and unloading, these double network hydrogels also exhibit a substantial rate-sensitive response during loading, but exhibit almost no rate-sensitivity during unloading. These features of large hysteresis and asymmetric rate-sensitivity are quite different from the response of conventional hydrogels. We limit our attention to modeling the complex viscoelastic response of such hydrogels under isothermal conditions. Our model is restricted in the sense that we have limited our attention to conditions under which one might neglect any diffusion of the water in the hydrogel - as might occur when the gel has a uniform initial value of the concentration of water, and the mobility of the water molecules in the gel is low relative to the time scale of the mechanical deformation. We also do not attempt to model the final fracture of such double-network hydrogels.

Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy

PubMed Central

Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Aquino, Rita P.; Del Gaudio, Pasquale

2016-01-01

In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps) able to delay steroidal anti-inflammatory drug (SAID) release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads) were manufactured using prilling (laminar jet break-up) as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v) amount and drug/polymer ratio (1:5 w/w) gave rise to the highest encapsulation efficiency (78.5%) as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6%) and delayed drug release up to about 390 minutes. PMID:27472446

A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion ligands regulates 3D spatial organization of cells and tissue.

PubMed

Lee, Min Kyung; Rich, Max H; Lee, Jonghwi; Kong, Hyunjoon

2015-07-01

Bioactive hydrogels have been extensively studied as a platform for 3D cell culture and tissue regeneration. One of the key desired design parameters is the ability to control spatial organization of biomolecules and cells and subsequent tissue in a 3D matrix. To this end, this study presents a simple but advanced method to spatially organize microchanneled, cell adherent gel blocks and non-adherent ones in a single construct. This hydrogel system was prepared by first fabricating a bimodal hydrogel in which the microscale, alginate gel blocks modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD peptides), and those free of RGD peptides, were alternatingly presented. Then, anisotropically aligned microchannels were introduced by uniaxial freeze-drying of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal cells to adhere to and differentiate into neuron and glial cells exclusively in microchannels of the alginate gel blocks modified with RGD peptides. Separately, the bimodal gel loaded with microparticles releasing vascular endothelial growth factor stimulated vascular growth solely into microchannels of the RGD-alginate gel blocks in vivo. These results were not attained by the bimodal hydrogel fabricated to present randomly oriented micropores. Overall, the bimodal gel system could regulate spatial organization of nerve-like tissue or blood vessels at sub-micrometer length scale. We believe that the hydrogel assembly demonstrated in this study will be highly useful in developing a better understanding of diverse cellular behaviors in 3D tissue and further improve quality of a wide array of engineered tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity.

PubMed

Yasasvini, S; Anusa, R S; VedhaHari, B N; Prabhu, P C; RamyaDevi, D

2017-03-01

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Advanced imaging approaches for characterizing nanoparticle delivery and dispersion in skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prow, Tarl W.; Yamada, Miko; Dang, Nhung; Evans, Conor L.

2017-02-01

The purpose of this research was to develop advanced imaging approaches to characterise the combination of elongated silica microparticles (EMP) and nanoparticles to control topical delivery of drugs and peptides. The microparticles penetrate through the epidermis and stop at the dermal-epidermal junction (DEJ). In this study we incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into the nanoparticle for visualization with microscopy. In another nanoparticle-based approach we utilized a chemically functionalized melanin nanoparticle for peptide delivery. These nanoparticles were imaged by coherent anti-Stoke Raman scattering (CARS) microscopy to characterize the delivery of these nanoparticles into freshly excised human skin. We compared four different coating approaches to combine EMP and nanoparticles. These data showed that a freeze-dried formulation with cross-linked alginate resulted in 100% of the detectable nanoparticle retained on the EMP. When this dry form of EMP-nanoparticle was applied to excised, living human abdominal skin, the EMP penetrated to the DEJ followed by controlled release of the nanoparticles. This formulation resulted in a sustained release profile, whereas a freeze-dried formulation without crosslinking showed an immediate burst-type release profile. These data show that advanced imaging techniques can give unique, label free data that shows promise for clinical investigations.

Shape-tunable wax microparticle synthesis via microfluidics and droplet impact

PubMed Central

Lee, Doojin; Beesabathuni, Shilpa N.; Shen, Amy Q.

2015-01-01

Spherical and non-spherical wax microparticles are generated by employing a facile two-step droplet microfluidic process which consists of the formation of molten wax microdroplets in a flow-focusing microchannel and their subsequent off-chip crystallization and deformation via microdroplet impingement on an immiscible liquid interface. Key parameters on the formation of molten wax microdroplets in a microfluidic channel are the viscosity of the molten wax and the interfacial tension between the dispersed and continuous fluids. A cursory phase diagram of wax morphology transition is depicted depending on the Capillary number and the Stefan number during the impact process. A combination of numerical simulation and analytical modeling is carried out to understand the physics underlying the deformation and crystallization process of the molten wax. The deformation of wax microdroplets is dominated by the viscous and thermal effects rather than the gravitational and buoyancy effects. Non-isothermal crystallization kinetics of the wax illustrates the time dependent thermal effects on the droplet deformation and crystallization. The work presented here will benefit those interested in the design and production criteria of soft non-spherical particles (i.e., alginate gels, wax, and polymer particles) with the aid of time and temperature mediated solidification and off-chip crosslinking. PMID:26697124

[Polyelectrolyte microcapsules as systems for delivery of biologically active substances].

PubMed

Borodina, T N; Rumsh, L D; Kunizhev, S M; Sukhorukov, G B; Vorozhtsov, G N; Fel'dman, B M; Markvicheva, E A

2007-01-01

Novel biodegradable microcapsules for delivery of biologically active substances (BAS) were prepared by layer-by-layer (LbL) adsorption of oppositely charged polyelectrolytes, namely sodium alginate (Alg) and poly-L-lysine (PLL). To immobilize these BAS, porous spherical CaCO3 microparticles were used as templates. The templates (cores) were coated with several layers of oppositely charged polyelectrolytes forming shell on a core surface. The core-shell microparticles were converted into hollow microcapsules by a core dissolution after an EDTA treatment. Mild conditions for microcapsule fabrication allow to perform an entrapment of various biomolecules while keeping their bioactivity. Biocompatibility and biodegradable capability of the polyelectrolytes give a possibility to use the microcapsules as the target delivery systems. Chymotrypsin (Chym) entrapped into the microcapsules was used as a model enzyme. The immobilized enzyme was found to keep about 86% of the activity compared to a native Chym. The obtained microcapsules were stable at an acidic medium while they could be easily decomposed by trypsin treatment at an slightly alkaline medium. Chym was shown to be active after being released from the microcapsules decomposed by trypsin treatment. Thus, the microcapsules prepared by the LbL - technique can be used for the development of new type of BAS delivery systems in humans and animals.

Disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules via covalent layer-by-layer assembly.

PubMed

Mu, Bin; Lu, Chunyin; Liu, Peng

2011-02-01

The disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules have been fabricated via the covalent layer-by-layer assembly between the amino groups of chitosan (CS) and the aldehyde groups of the oxidized sodium alginate (OSA) onto the sacrificial templates (polystyrene sulfonate, PSS) which was removed by dialysis subsequently. The covalent crosslinking bonds of the multilayer microcapsules were confirmed by FTIR analysis. The TEM analysis showed that the diameter of the multilayer microcapsules was <200nm. The diameter of the multilayer microcapsules decreased with the increasing of the pH values or the ionic strength. The pH and ionic strength dual-responsive multilayer microcapsules were stable in acidic and neutral media while they could disintegrate only at strong basic media. Copyright © 2010 Elsevier B.V. All rights reserved.

Aging effects on chemical transformation and metal(loid) removal by entrapped nanoscale zero-valent iron for hydraulic fracturing wastewater treatment.

PubMed

Sun, Yuqing; Lei, Cheng; Khan, Eakalak; Chen, Season S; Tsang, Daniel C W; Ok, Yong Sik; Lin, Daohui; Feng, Yujie; Li, Xiang-Dong

2018-02-15

In this study, alginate and polyvinyl alcohol (PVA)-alginate entrapped nanoscale zero-valent iron (nZVI) was tested for structural evolution, chemical transformation, and metals/metalloids removal (Cu(II), Cr(VI), Zn(II), and As(V)) after 1-2month passivation in model saline wastewaters from hydraulic fracturing. X-ray diffraction analysis confirmed successful prevention of Fe 0 corrosion by polymeric entrapment. Increasing ionic strength (I) from 0 to 4.10M (deionized water to Day-90 fracturing wastewater (FWW)) with prolonged aging time induced chemical instability of alginate due to dissociation of carboxyl groups and competition for hydrogen bonding with nZVI, which caused high Na (7.17%) and total organic carbon (24.6%) dissolution from PVA-alginate entrapped nZVI after 2-month immersion in Day-90 FWW. Compared to freshly-made beads, 2-month aging of PVA-alginate entrapped nZVI in Day-90 FWW promoted Cu(II) and Cr(VI) uptake in terms of the highest removal efficiency (84.2% and 70.8%), pseudo-second-order surface area-normalized rate coefficient k sa (2.09×10 -1 Lm -2 h -1 and 1.84×10 -1 Lm -2 h -1 ), and Fe dissolution after 8-h reaction (13.9% and 8.45%). However, the same conditions inhibited Zn(II) and As(V) sequestration in terms of the lowest removal efficiency (31.2% and 39.8%) by PVA-alginate nZVI and k sa (4.74×10 -2 Lm -2 h -1 and 6.15×10 -2 Lm -2 h -1 ) by alginate nZVI. The X-ray spectroscopic analysis and chemical speciation modelling demonstrated that the difference in metals/metalloids removal by entrapped nZVI after aging was attributed to distinctive removal mechanisms: (i) enhanced Cu(II) and Cr(VI) removal by nZVI reduction with accelerated electron transfer after pronounced dissolution of non-conductive polymeric immobilization matrix; (ii) suppressed Zn(II) and As(V) removal by nZVI adsorption due to restrained mass transfer after blockage of surface-active micropores. Entrapped nZVI was chemically fragile and should be properly stored and regularly replaced for good performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Biosorption of metal ions from aqueous solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jiaping; Yiacoumi, Sotira

1997-01-01

Copper biosorption from aqueous solutions by calcium alginate is reported in this paper. The experimental section includes potentiometric titrations of biosorbents, batch equilibrium and kinetic studies of copper biosorption, as well as fixed-bed biosorption experiments. The potentiometric titration results show that the surface charge increases with decreasing pH. The biosorption of copper strongly depends on solution pH; the metal ion binding increases from 0 to 90 percent in pH ranging from 1.5 to 5.0. In addition, a decrease in ionic strength results in an increase of copper ion removal. Kinetic studies indicate that mass transfer plays an important role inmore » the biosorption rate. Furthermore, a fixed-bed biosorption experiment shows that calcium alginate has a significant capacity for copper ion removal. The two-pK Basic Stem model successfully represents the surface charge and equilibrium biosorption experimental data. The calculation results demonstrate that the copper removal may result from the binding of free copper and its hydroxide with surface functional groups of the biosorbents.« less

Therapeutic effect of orally administered microencapsulated oxaliplatin for colorectal cancer

PubMed Central

Urbanska, Aleksandra M.; Karagiannis, Emmanouil D.; Guajardo, Gonzalo; Langer, Robert S.; Anderson, Daniel G.

2013-01-01

Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Oral delivery of therapeutics remains the most patient accepted form of medication. The development of an oral delivery formulation for local delivery of chemotherapeutics in the gastrointestinal tract can potentially alleviate the adverse side effects including systemic cytotoxicity, as well as focus therapy to the lesions. Here we develop an oral formulation of the chemotherapeutic drug oxaliplatin for the treatment of colorectal cancer. Oxaliplatin was encapsulated in pH sensitive, mucoadhesive chitosan-coated alginate microspheres. The microparticles were formulated to release the chemotherapeutics after passing through the acidic gastric environment thus targeting the intestinal tract. In vivo, these particles substantially reduced the tumor burden in an orthotopic mouse model of colorectal cancer, and reduced mortality. PMID:22472433

Fabrication of uniform multi-compartment particles using microfludic electrospray technology for cell co-culture studies.

PubMed

Liu, Zhou; Shum, Ho Cheung

2013-01-01

In this work, we demonstrate a robust and reliable approach to fabricate multi-compartment particles for cell co-culture studies. By taking advantage of the laminar flow within our microfluidic nozzle, multiple parallel streams of liquids flow towards the nozzle without significant mixing. Afterwards, the multiple parallel streams merge into a single stream, which is sprayed into air, forming monodisperse droplets under an electric field with a high field strength. The resultant multi-compartment droplets are subsequently cross-linked in a calcium chloride solution to form calcium alginate micro-particles with multiple compartments. Each compartment of the particles can be used for encapsulating different types of cells or biological cell factors. These hydrogel particles with cross-linked alginate chains show similarity in the physical and mechanical environment as the extracellular matrix of biological cells. Thus, the multi-compartment particles provide a promising platform for cell studies and co-culture of different cells. In our study, cells are encapsulated in the multi-compartment particles and the viability of cells is quantified using a fluorescence microscope after the cells are stained for a live/dead assay. The high cell viability after encapsulation indicates the cytocompatibility and feasibility of our technique. Our multi-compartment particles have great potential as a platform for studying cell-cell interactions as well as interactions of cells with extracellular factors.

Fabrication of uniform multi-compartment particles using microfludic electrospray technology for cell co-culture studies

PubMed Central

Liu, Zhou; Shum, Ho Cheung

2013-01-01

In this work, we demonstrate a robust and reliable approach to fabricate multi-compartment particles for cell co-culture studies. By taking advantage of the laminar flow within our microfluidic nozzle, multiple parallel streams of liquids flow towards the nozzle without significant mixing. Afterwards, the multiple parallel streams merge into a single stream, which is sprayed into air, forming monodisperse droplets under an electric field with a high field strength. The resultant multi-compartment droplets are subsequently cross-linked in a calcium chloride solution to form calcium alginate micro-particles with multiple compartments. Each compartment of the particles can be used for encapsulating different types of cells or biological cell factors. These hydrogel particles with cross-linked alginate chains show similarity in the physical and mechanical environment as the extracellular matrix of biological cells. Thus, the multi-compartment particles provide a promising platform for cell studies and co-culture of different cells. In our study, cells are encapsulated in the multi-compartment particles and the viability of cells is quantified using a fluorescence microscope after the cells are stained for a live/dead assay. The high cell viability after encapsulation indicates the cytocompatibility and feasibility of our technique. Our multi-compartment particles have great potential as a platform for studying cell-cell interactions as well as interactions of cells with extracellular factors. PMID:24404050

Pb(II) adsorption by a novel activated carbon - alginate composite material. A kinetic and equilibrium study.

PubMed

Cataldo, Salvatore; Gianguzza, Antonio; Milea, Demetrio; Muratore, Nicola; Pettignano, Alberto

2016-11-01

The adsorption capacity of an activated carbon - calcium alginate composite material (ACAA-Ca) has been tested with the aim of developing a new and more efficient adsorbent material to remove Pb(II) ion from aqueous solution. The study was carried out at pH=5, in NaCl medium and in the ionic strength range 0.1-0.75molL -1 . Differential Pulse Anodic Stripping Voltammetry (DP-ASV) technique was used to check the amount of Pb(II) ion removed during kinetic and equilibrium experiments. Different kinetic (pseudo first order, pseudo second order and Vermuelen) and equilibrium (Langmuir and Freundlich) models were used to fit experimental data, and were statistically compared. Calcium alginate (AA-Ca) improves the adsorption capacity (q m ) of active carbon (AC) in the ACAA-Ca adsorbent material (e.g., q m =15.7 and 10.5mgg -1 at I=0.25molL -1 , for ACAA-Ca and AC, respectively). SEM-EDX and thermogravimetric (TGA) measurements were carried out in order to characterize the composite material. The results of the speciation study on the Pb(II) solution and of the characterization of the ACAA-Ca and of the pristine AA-Ca and AC were evaluated in order to explain the specific contribution of AC and AA-Ca to the adsorption of the metal ion. Copyright © 2016 Elsevier B.V. All rights reserved.

Sodium alginate/graphene oxide hydrogel beads as permeable reactive barrier material for the remediation of ciprofloxacin-contaminated groundwater.

PubMed

Zhao, Pingping; Yu, Fei; Wang, Ruoyu; Ma, Yao; Wu, Yanqing

2018-06-01

The wide occurrence of antibiotics in groundwater has raised serious concerns due to their impacts on humans and the ecosystem. Most of the research in groundwater remediation focuses on the exploitation of nano-materials. However, nano-materials have several disadvantages such as high production cost, rapid reduction in permeability, disposal problems, and high sensitivity to environmental conditions. To solve these issues, novel sodium alginate/graphene oxide hydrogel beads (GSA) were synthesised and their effectiveness as permeable reactive barrier (PRB) backfill material in the remediation of ciprofloxacin (CPX)-contaminated groundwater was tested. The adsorption of CPX onto GSA followed the pseudo-second-order kinetic model. The isotherm data followed the Freundlich model. The maximum adsorption capacity was 100 mg g -1 at pH 7.0. The adsorption process was sensitive to contact time, initial CPX concentration and ionic strength. However, it was not pH sensitive. Hydrophobic interaction, electrostatic interaction, ion exchange, H-bonding, and pore filling were proposed to be the main adsorption mechanisms. The effects of flow rate, influent CPX concentration, and ionic strength on the performance of PRB were confirmed through flow-through column experiments and by using a chemical non-equilibrium two-site model. Accordingly, a proper PRB was designed based on hydrogeological conditions. Finally, the lifetime and cost of the PRBs were calculated. The results obtained provided concrete evidence that GSA is a promising adsorbent material for PRBs applications in the remediation of CPX-contaminated groundwater. Copyright © 2018 Elsevier Ltd. All rights reserved.

Choline chloride-thiourea, a deep eutectic solvent for the production of chitin nanofibers.

PubMed

Mukesh, Chandrakant; Mondal, Dibyendu; Sharma, Mukesh; Prasad, Kamalesh

2014-03-15

Deep eutectic solvents (DESs) consisting of the mixtures of choline halide (chloride/bromide)-urea and choline chloride-thiourea were used as solvents to prepare α-chitin nanofibers (CNFs). CNFs of diameter 20-30 nm could be obtained using the DESs comprising of the mixture of choline chloride and thiourea (CCT 1:2); however, NFs could not be obtained using the DESs having urea (CCU 1:2) as hydrogen bond donor. The physicochemical properties of thus obtained NFs were compared with those obtained using a couple of imidazolium based ionic liquids namely, 1-butyl-3-methylimidazolium hydrogen sulphate [(Bmim)HSO4] and 1-methylimidazolium hydrogen sulphate [(Hmim)HSO4] as well as choline based bio-ILs namely, choline hydrogen sulphate [(Chol)HSO4] and choline acrylate. The CNFs obtained using the DES as a solvent were used to prepare calcium alginate bio-nanocomposite gel beads having enhanced elasticity in comparison to Ca-alginate beads. The bio-nanocomposite gel beads thus obtained were used to study slow release of 5-fluorouracil, an anticancer drug. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultra-tough and strong, hybrid thin films based on ionically crosslinked polymers and 2D inorganic platelets

NASA Astrophysics Data System (ADS)

Ji, Dong Hwan; Choi, Suji; Kim, Jaeyun; nanobiomaterials lab Team

Integration of high strength and toughness tend to be mutually exclusive and synthesized hybrid films with superior mechanical properties have been difficult to fabricate controllable shapes and various scales. Although diverse synthesized hybrid films consisting of organic matrix and inorganic materials with brick-and-mortar structure, show improved mechanical properties, these films are still limited in toughness and fabrication methods. Herein, we report ultra-tough and strong hybrid thin films with self-assembled uniform microstructures with controllable shapes and various scale based on hydrogel-mediated process. Ca2+-crosslinking in alginate chains and well-aligned alumina platelets in alginate matrix lead to a synergistic enhancement of strength and toughness in the resulting film. Consequentially, Ca2+-crosslinked Alg/Alu films showed outstanding toughness of 29 MJ m-3 and tensile strength of 160 MPa. Furthermore, modifying Alu surface with polyvinylpyrrolidone (PVP), tensile strength was further improved up to 200 MPa. Our results suggest an alternative approach to design and processing of self-assembled hydrogel-mediated hybrid films with outstanding mechanical properties.

Fast decolorization of azo methyl orange via heterogeneous Fenton and Fenton-like reactions using alginate-Fe2+/Fe3+ films as catalysts.

PubMed

Quadrado, Rafael F N; Fajardo, André R

2017-12-01

The efficiency of Fenton and Fenton-like processes can be seriously affected by the continuous loss of iron ions and by the formation of solid sludge. Here, alginate (Alg) films were synthesized to stabilize iron ions (Fe 2+ and Fe 3+ ) and to enhance their catalytic activities towards the decolorization of methyl orange via heterogeneous Fenton and Fenton-like processes. Iron ions were ionically bond to the Alg molecules resulting in a three-dimensional network with specific structural and morphological features according to the valence states of iron. Our results demonstrated that both Alg-Fe 2+ and Alg-Fe 3+ films show highlighted catalytic activity for the decolorization of MO and high decolorization rates. Reuse experiments demonstrated that both films could be employed in at least five consecutive decolorization processes without losing their catalytic efficiency or stability. Taken together, our findings reveal that the Alg-Fe 2+ and Alg-Fe 3+ films may be suitable low-cost catalysts in heterogeneous Fenton and Fenton-like processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Semi-Degradable Composite Scaffold for Articular Cartilage Defects

PubMed Central

Scholten, Paul M.; Ng, Kenneth W.; Joh, Kiwon; Serino, Lorenzo P.; Warren, Russell F.; Torzilli, Peter A.; Maher, Suzanne A.

2010-01-01

Few options exist to replace or repair damaged articular cartilage. The optimal solution that has been suggested is a scaffold that can carry load and integrate with surrounding tissues; but such a construct has thus far been elusive. The objectives of this study were to manufacture and characterize a non-degradable hydrated scaffold. Our hypothesis was that the polymer content of the scaffold can be used to control its mechanical properties, while an internal porous network augmented with biological agents can facilitate integration with the host tissue. Using a two-step water-in-oil emulsion process a porous poly-vinyl alcohol (PVA) hydrogel scaffold combined with alginate microspheres was manufactured. The scaffold had a porosity of 11–30% with pore diameters of 107–187 μm, which readily allowed for movement of cells through the scaffold. Alginate microparticles were evenly distributed through the scaffold and allowed for the slow release of biological factors. The elastic modulus (Es) and Poisson’s ratio (υ), Aggregate modulus (Ha) and dynamic modulus (ED) of the scaffold were significantly affected by % PVA, as it varied from 10% to 20% wt/vol. Es and υ were similar to that of articular cartilage for both polymer concentrations, while Ha and ED were similar to that of cartilage only at 20% PVA. The ability to control scaffold mechanical properties, while facilitating cellular migration suggest that this scaffold is a potentially viable candidate for the functional replacement of cartilage defects. PMID:21308980

Controls of ionic strength and macromolecule chemistry on calcite nucleation: Salinity and ion hydration as levers for regulating biomineralization

NASA Astrophysics Data System (ADS)

Dove, P. M.; Giuffre, A. J.; Mergelsberg, S. T.; Han, N.; De Yoreo, J. J.

2016-12-01

Organisms form shells and skeletons with remarkable fidelity by controlling the timing and placement of the minerals that nucleate and subsequently grow. An extensive effort has identified features of the organic matrix that regulate this process. Recent measurements from our group show the energy barrier to nucleation onto polysaccharide (PS) substrates is dependent upon hydrophilicity through functional group chemistry and suggest that free energy of the macromolecule-liquid interface influences where and when mineral nucleation occurs (Giuffre et al., 2013, PNAS). The importance of interfacial free energy in regulating nucleation raises the question of whether local changes in salinity or electrolyte composition can be tuned to further modulate the onset of calcite nucleation. Using alginate (negatively charged by carboxyl groups) and chitosan (small positive charge by amine groups), the rate of calcite nucleation was measured at controlled supersaturations and pH as a function of NaCl concentration (65-600 mM). Analyses of the data show the thermodynamic barrier to calcite nucleation onto both types of PS increases with ionic strength. The evidence suggests this effect arises from an increasing concentration of solvated ions at the PS-water interface while also increasing the hydrophilic character of that interface; thus decreasing the substrate-liquid interfacial free energy. To test this explanation, a second group of nucleation experiments used a suite of electrolytes (alkali chlorides for alginate and sodium halides for chitosan) while holding ionic strength constant. Indeed, the nucleation barriers for calcite formation are electrolyte-specific and correlated with the hydration free energy of the ion. This suggests solvated electrolyte ions indirectly regulate calcite nucleation onto substrates through their competition with the substrate for water thereby influencing net interfacial free energy. These effects are consistent with the long-established salting-in phenomena of the Hofmeister series. The new insights from this experimental study reiterate the importance of electrolytes in reactions involving mineral-water interfaces and suggest a role for seemingly inert `spectator' ions in regulating the local timing and placement of minerals during biomineralization.

Heterogeneous electro-Fenton catalyst for 1-butylpyridinium chloride degradation.

PubMed

Meijide, Jessica; Pazos, Marta; Sanromán, Maria Ángeles

2017-10-15

The application of the electro-Fenton process for organic compound mineralisation has been widely reported over the past years. However, operational problems related to the use of soluble iron salt as a homogeneous catalyst involve the development of novel catalysts that are able to operate in a wide pH range. For this purpose, polyvinyl alcohol-alginate beads, containing goethite as iron, were synthesised and evaluated as heterogeneous electro-Fenton catalyst for 1-butylpyridinium chloride mineralisation. The influence of catalyst dosage and pH solution on ionic liquid degradation was analysed, achieving almost total oxidation after 60 min under optimal conditions (2 g/L catalyst concentration and pH 3). The results showed good catalyst stability and reusability, although its effectiveness decreases slightly after three successive cycles. Furthermore, a plausible mineralisation pathway was proposed based on the oxidation byproducts determined by chromatographic techniques. Finally, the Microtox® test revealed notable detoxification after treatment which demonstrates high catalyst ability for pyridinium-based ionic liquid degradation by the electro-Fenton process.

Size-Dependent Neurotoxicity of Aluminum Oxide Particles: a Comparison Between Nano- and Micrometer Size on the Basis of Mitochondrial Oxidative Damage.

PubMed

Mirshafa, Atefeh; Nazari, Mehdi; Jahani, Daniel; Shaki, Fatemeh

2018-06-01

Aluminum nanoparticles (AlNPs) are among the most abundantly produced nanosized particles in the market. There is limited information about the potential harmful effects of aluminum oxide due to its particle size on human health. Considering the toxic effects of Al on brain as its target tissue, in this study, the toxicity of nanoparticles, microparticles, and ionic forms of Al on rat brain and isolated mitochondria was evaluated. Sixty male Wistar rats were divided into ten groups (six rats each), in which group I was the control, and the other groups were administered different doses of Al nanoparticles, Al microparticles (AlMP), and Al ionic forms (2, 4, and 8 mg/kg, i.p.) for 28 days. After 24 h, the animals were killed, brain tissue was separated, the mitochondrial fraction was isolated, and oxidative stress markers were measured. Also, mitochondrial function was assayed by MTT test. The results showed that all forms of Al particles induced ROS formation, lipid peroxidation, protein oxidation, glutathione depletion, mitochondrial dysfunction, and gait abnormalities in a dose-dependent manner. In addition, Al particles decreased mitochondrial membrane potential. These data indicated that oxidative stress might contribute to the toxicity effects of Al. Comparison of oxidative stress markers between all forms of Al revealed that the toxic effect of AlNP on brain tissue was substantially more than that caused by AlMP and bulk form. This study showed more neurotoxicity of AlNPs compared to other forms on brain oxidative damage that probably is due to more penetration into the brain.

A robust salt-tolerant superoleophobic alginate/graphene oxide aerogel for efficient oil/water separation in marine environments

NASA Astrophysics Data System (ADS)

Li, Yuqi; Zhang, Hui; Fan, Mizi; Zheng, Peitao; Zhuang, Jiandong; Chen, Lihui

2017-04-01

Marine pollution caused by frequent oil spill accidents has brought about tremendous damages to marine ecological environment. Therefore, the facile large-scale preparation of three-dimensional (3D) porous functional materials with special wettability is in urgent demand. In this study, we report a low-cost and salt-tolerant superoleophobic aerogel for efficient oil/seawater separation. The aerogel is prepared through incorporating graphene oxide (GO) into alginate (ALG) matrix by using a facile combined freeze-drying and ionic cross-linking method. The 3D structure interconnected by ALG and GO ensures the high mechanical strength and good flexibility of the developed aerogel. The rough microstructure combined with the hydrophilicity of the aerogel ensures its excellent underwater superoleophobic and antifouling properties. High-content polysaccharides contained in the aerogel guarantees its excellent salt-tolerant property. More impressively, the developed aerogel can retain its underwater superoleophobicity even after 30 days of immersion in seawater, indicating its good stability in marine environments. Furthermore, the aerogel could separate various oil/water mixtures with high separation efficiency (>99%) and good reusability (at least 40 cycles). The facile fabrication process combined with the excellent separation performance makes it promising for practical applications in marine environments.

Preparation and modification of N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride nanoparticle as a protein carrier.

PubMed

Xu, Yongmei; Du, Yumin; Huang, Ronghua; Gao, Leping

2003-12-01

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is water-soluble derivative of chitosan (CS), synthesized by the reaction between glycidyl-trimethyl-ammonium chloride and CS. HTCC nanoparticles have been formed based on ionic gelation process of HTCC and sodium tripolyphosphate (TPP). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the HTCC nanoparticles. HTCC nanoparticles were 110-180 nm in size, and their encapsulation efficiency was up to 90%. In vitro release studies showed a burst effect and a slow and continuous release followed. Encapsulation efficiency was obviously increased with increase of initial BSA concentration. Increasing TPP concentration from 0.5 to 0.7 mg/ml promoted encapsulation efficiency from 46.7% to 90%, and delayed release. As for modified HTCC nanoparticles, adding polyethylene glycol (PEG) or sodium alginate obviously decreased the burst effect of BSA from 42% to 18%. Encapsulation efficiency was significantly reduced from 47.6% to 2% with increase of PEG from 1.0 to 20.0 mg/ml. Encapsulation efficiency was increased from 14.5% to 25.4% with increase of alginate from 0.3 to 1.0 mg/ml.

Fabrication of granular activated carbons derived from spent coffee grounds by entrapment in calcium alginate beads for adsorption of acid orange 7 and methylene blue.

PubMed

Jung, Kyung-Won; Choi, Brian Hyun; Hwang, Min-Jin; Jeong, Tae-Un; Ahn, Kyu-Hong

2016-11-01

Biomass-based granular activated carbon was successfully prepared by entrapping activated carbon powder derived from spent coffee grounds into calcium-alginate beads (SCG-GAC) for the removal of acid orange 7 (AO7) and methylene blue (MB) from aqueous media. The dye adsorption process is highly pH-dependent and essentially independent of ionic effects. The adsorption kinetics was satisfactorily described by the pore diffusion model, which revealed that pore diffusion was the rate-limiting step during the adsorption process. The equilibrium isotherm and isosteric heat of adsorption indicate that SCG-GAC possesses an energetically heterogeneous surface and operates via endothermic process in nature. The maximum adsorption capacities of SCG-GAC for AO7 (pH 3.0) and MB (pH 11.0) adsorption were found to be 665.9 and 986.8mg/g at 30°C, respectively. Lastly, regeneration tests further confirmed that SCG-GAC has promising potential in its reusability, showing removal efficiency of more than 80% even after seven consecutive cycles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chitin's Functionality as a Novel Disintegrant: Benchmarking Against Commonly Used Disintegrants in Different Physicochemical Environments.

PubMed

Chaheen, Mohammad; Soulairol, Ian; Bataille, Bernard; Yassine, Ahmad; Belamie, Emmanuel; Sharkawi, Tahmer

2017-07-01

Disintegrants are used as excipients to ensure rapid disintegration of pharmaceutical tablets and further ensure proper dissolution of the active pharmaceutical ingredient. This study investigates disintegration mechanisms of chitin and common disintegrants. Swelling assessment (swelling force and swelling ratio) in different media, and compaction behavior (pure or mixed with other excipients) tabletability, deformation (Heckel modeling), and compact disintegration times were investigated on the tested disintegrants (alginic acid calcium salt, crospovidone, sodium starch glycolate, croscarmellose sodium, and chitin). Results show that the physicochemical properties of the disintegration medium such as pH and ionic strength, as well as other formulation ingredients, affect the disintegrant functionalities. Heckel analysis using the mean yield pressure "Py" shows that alginic acid calcium salt is the most brittle among the studied disintegrants, while crospovidone has the most plastic deformation mechanism, followed by chitin. Chitin showed good tabletability and disintegration properties that were not influenced by the physicochemical formulation environment. Chitin is largely available and easily modifiable and thus a promising material that could be used as a multifunctional excipient in tablet formulation. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Development of a P((MAA-co-NVP)-g-EG) Hydrogel Platform for Oral Protein Delivery: Effects of Hydrogel Composition on Environmental Response and Protein Partitioning.

PubMed

Steichen, Stephanie; O'Connor, Colleen; Peppas, Nicholas A

2017-01-01

Hydrogels based upon terpolymers of methacrylic acid, N-vinyl pyrrolidone, and poly(ethylene glycol) are developed and characterized for their ability to respond to changes in environmental pH and to partition protein therapeutics of varying molecular weights and isoelectric points. P((MAA-co-NVP)-g-EG) hydrogels are synthesized with PEG-based cross-linking agents of varying length and incorporation densities. The composition is confirmed using FT-IR spectroscopy and shows peak shifts indicating hydrogen bonding. Scanning electron microscopy reveals microparticles with an irregular, planar morphology. The pH-responsive behavior of the hydrogels is confirmed under equilibrium and dynamic conditions, with the hydrogel collapsed at acidic pH and swollen at neutral pH. The ability of the hydrogels to partition model protein therapeutics at varying pH and ionic strength is evaluated using three model proteins: insulin, porcine growth hormone, and ovalbumin. Finally, the microparticles are evaluated for adverse interactions with two model intestinal cell lines and show minimal cytotoxicity at concentrations below 5 mg mL -1 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of the ionic interaction between the hydrophobin RodA and two cutinases of Aspergillus nidulans obtained via an Aspergillus oryzae expression system.

PubMed

Tanaka, Takumi; Nakayama, Mayumi; Takahashi, Toru; Nanatani, Kei; Yamagata, Youhei; Abe, Keietsu

2017-03-01

Hydrophobins are amphipathic secretory proteins with eight conserved cysteine residues and are ubiquitous among filamentous fungi. In the fungus Aspergillus oryzae, the hydrophobin RolA and the polyesterase CutL1 are co-expressed when the sole available carbon source is the biodegradable polyester polybutylene succinate-co-adipate (PBSA). RolA promotes the degradation of PBSA by attaching to the particle surface, changing its structure and interacting with CutL1 to concentrate CutL1 on the PBSA surface. We previously reported that positively charged residues in RolA and negatively charged residues in CutL1 are cooperatively involved in the ionic interaction between RolA and CutL1. We also reported that hydrophobin RodA of the model fungus Aspergillus nidulans, which was obtained via an A. oryzae expression system, interacted via ionic interactions with CutL1. In the present study, phylogenetic and alignment analyses revealed that the N-terminal regions of several RolA orthologs contained positively charged residues and that the corresponding negatively charged residues on the surface of CutL1 that were essential for the RolA-CutL1 interaction were highly conserved in several CutL1 orthologs. A PBSA microparticle degradation assay, a pull-down assay using a dispersion of Teflon particles, and a kinetic analysis using a quartz crystal microbalance revealed that recombinant A. nidulans RodA interacted via ionic interactions with two recombinant A. nidulans cutinases. Together, these results imply that ionic interactions between hydrophobins and cutinases may be common among aspergilli and other filamentous fungi.

Extraction of Structural Extracellular Polymeric Substances from Aerobic Granular Sludge

PubMed Central

Felz, Simon; Al-Zuhairy, Salah; Aarstad, Olav Andreas; van Loosdrecht, Mark C.M.; Lin, Yue Mei

2016-01-01

To evaluate and develop methodologies for the extraction of gel-forming extracellular polymeric substances (EPS), EPS from aerobic granular sludge (AGS) was extracted using six different methods (centrifugation, sonication, ethylenediaminetetraacetic acid (EDTA), formamide with sodium hydroxide (NaOH), formaldehyde with NaOH and sodium carbonate (Na2CO3) with heat and constant mixing). AGS was collected from a pilot wastewater treatment reactor. The ionic gel-forming property of the extracted EPS of the six different extraction methods was tested with calcium ions (Ca2+). From the six extraction methods used, only the Na2CO3 extraction could solubilize the hydrogel matrix of AGS. The alginate-like extracellular polymers (ALE) recovered with this method formed ionic gel beads with Ca2+. The Ca2+-ALE beads were stable in EDTA, formamide with NaOH and formaldehyde with NaOH, indicating that ALE are one part of the structural polymers in EPS. It is recommended to use an extraction method that combines physical and chemical treatment to solubilize AGS and extract structural EPS. PMID:27768085

Preparation of curcumin nanoparticle by using reinforcement ionic gelation technique

NASA Astrophysics Data System (ADS)

Suryani, Halid, Nur Hatidjah Awaliyah; Akib, Nur Illiyyin; Rahmanpiu, Mutmainnah, Nina

2017-05-01

Curcumin, a polyphenolic compound present in curcuma longa has a wide range of activities including anti-inflammatory properties. The potency of curcumin is limited by its poor oral bioavailability because of its poor solubility in aqueous. Various methods have been tried to solve the problem including its encapsulation into nanoparticle. The aim of this study is to develop curcumin nanoparticle by using reinforcement ionic gelation technique and to evaluate the stability of curcumin nanoparticles in gastrointestinal fluid. Curcumin nanoparticles were prepared by using reinforcement ionic gelation technique with different concentrations of chitosan, trypolyphosphate, natrium alginate and calcium chloride. Curcumin nanoparticles were then characterized including particle size and zeta potential by using particle size analyzer and morphology using a transmission electron microscope, entrapment efficiency using UV-Vis Spectrophotometer and chemical structure analysis by Infra Red Spectrophotometer (FTIR). Furthermore, the stability of curcumin nanoparticles were evaluated on artificial gastric fluid and artificial intestinal fluids by measuring the amount of curcumin released in the medium at a time interval. The result revealed that curcumin nanoparticles can be prepared by reinforcement ionic gelation technique, the entrapment efficiency of curcumin nanoparticles were from 86.08 to 91.41%. The average of particle size was 272.9 nm and zeta potential was 12.05 mV. The morphology examination showed that the curcumin nanoparticles have spherical shape. The stability evaluation of curcumin nanoparticles showed that the nanoparticles were stable on artificial gastric fluid and artificial intestinal fluid. This result indicates that curcumin nanoparticles have the potential to be developed for oral delivery.

Targeted Delivery of Chemotherapeutic Agents Using Improved Radiosensitive Liquid Core Microcapsules and Assessment of Their Antitumor Effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harada, Satoshi; Ehara, Shigeru; Ishii, Keizo

2009-10-01

Purpose: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. Methods and Materials: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 {mu}g) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl{sub 2} solution supplemented with 0-0.01% yttrium.more » These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy {sup 60}Co {gamma}-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. Results: Microcapsules that had been polymerized using a 4.34% CaCl{sub 2} solution supplemented with 5.0 x 10{sup -3}% (10{sup -3}% meant or 10%{sup -3}) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. Conclusion: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.« less

Cell-friendly inverse opal-like hydrogels for a spatially separated co-culture system.

PubMed

Kim, Jaeyun; Bencherif, Sidi A; Li, Weiwei Aileen; Mooney, David J

2014-09-01

Three-dimensional macroporous scaffolds have extensively been studied for cell-based tissue engineering but their use is mostly limited to mechanical support for cell adhesion and growth on the surface of macropores. Here, a templated fabrication method is described to prepare cell-friendly inverse opal-like hydrogels (IOHs) allowing both cell encapsulation within the hydrogel matrix and cell seeding on the surface of macropores. Ionically crosslinked alginate microbeads and photocrosslinkable biocompatible polymers are used as a sacrificial template and as a matrix, respectively. The alginate microbeads are easily removed by a chelating agent, with minimal toxicity for the encapsulated cells during template removal. The outer surface of macropores in IOHs can also provide a space for cell adherence. The cells encapsulated or attached in IOHs are able to remain viable and to proliferate over time. The elastic modulus and cell-adhesion properties of IOHs can be easily controlled and tuned. Finally, it is demonstrated that IOH can be used to co-culture two distinct cell populations in different spatial positions. This cell-friendly IOH system provides a 3D scaffold for organizing different cell types in a controllable microenvironment to investigate biological processes such as stem cell niches or tumor microenvironments. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A robust salt-tolerant superoleophobic alginate/graphene oxide aerogel for efficient oil/water separation in marine environments

PubMed Central

Li, Yuqi; Zhang, Hui; Fan, Mizi; Zheng, Peitao; Zhuang, Jiandong; Chen, Lihui

2017-01-01

Marine pollution caused by frequent oil spill accidents has brought about tremendous damages to marine ecological environment. Therefore, the facile large-scale preparation of three-dimensional (3D) porous functional materials with special wettability is in urgent demand. In this study, we report a low-cost and salt-tolerant superoleophobic aerogel for efficient oil/seawater separation. The aerogel is prepared through incorporating graphene oxide (GO) into alginate (ALG) matrix by using a facile combined freeze-drying and ionic cross-linking method. The 3D structure interconnected by ALG and GO ensures the high mechanical strength and good flexibility of the developed aerogel. The rough microstructure combined with the hydrophilicity of the aerogel ensures its excellent underwater superoleophobic and antifouling properties. High-content polysaccharides contained in the aerogel guarantees its excellent salt-tolerant property. More impressively, the developed aerogel can retain its underwater superoleophobicity even after 30 days of immersion in seawater, indicating its good stability in marine environments. Furthermore, the aerogel could separate various oil/water mixtures with high separation efficiency (>99%) and good reusability (at least 40 cycles). The facile fabrication process combined with the excellent separation performance makes it promising for practical applications in marine environments. PMID:28397862

Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery.

PubMed

Zhu, Xuan; Su, Meiqin; Tang, Shaoheng; Wang, Lingsong; Liang, Xinfang; Meng, Feihong; Hong, Ying; Xu, Zhiran

2012-01-01

The goal of the present study was to synthesize mucoadhesive polymer - thiolated chitosan (TCS) from chitosan (CS), then prepared CS/TCS-sodium alginate nanoparticles (CS/TCS-SA NPs), determined which was more potential for ocular drug delivery. A new method for preparing TCS was developed, and the characteristics were determined using Fourier transform infrared spectroscopy and the degree of thiol immobilized was measured by Ellman's reagent. Human corneal epithelium (HCE) cells were incubated with different concentrations of TCS for 48 h to determine the cell viabilities. CS/TCS-SA NPs were prepared and optimized by a modified ionic gelation method. The particle sizes, zeta potentials, Scanning electron microscopy images, mucoadhesion, in vitro cell uptake and in vivo studies of the two types of NP were compared. The new method enabled a high degree of thiol substitution of TCS, up to 1,411.01±4.02 μmol/g. In vitro cytocompatibility results suggest that TCS is nontoxic. Compared to CS-SA NPs, TCS-SA NPs were more stable, with higher mucoadhesive properties and could deliver greater amounts of drugs into HCE cells in vitro and cornea in vivo. TCS-SA NPs have better delivery capability, suggesting they have good potential for ocular drug delivery applications.

Enhanced removal of bisphenol-AF by activated carbon-alginate beads with cetyltrimethyl ammonium bromide.

PubMed

Tang, Zheng; Peng, Sha; Hu, Shuya; Hong, Song

2017-06-01

Adsorption removal of bisphenol-AF (BPAF) from aqueous solutions by synthesized activated carbon-alginate beads (AC-AB) with cetyltrimethyl ammonium bromide (CTAB) has been studied using two ways. The traditional method (two-step) first synthesized CTAB-modified AC-AB (AC-AB-CTAB), then used it to remove BPAF by adsorption. And one-step method dispersed AC-AB and CTAB in wastewater, followed by the removal of BPAF accompanied with the synthesis of AC-AB-CTAB. The one-step method showed a better performance than the two-step method, achieving a maximum removal of BPAF with 284.6mg/g. Kinetic studies and adsorption isotherms indicated that adsorption process of BPAF on AC-AB by the one-step method could be expressed by a pseudo-second-order model and a Dubinin-Ashtakhov (D-A) isotherm, respectively. The effects of pH, ionic strength, and inorganic ions on BPAF adsorption were also investigated. Furthermore, hydrophobic interactions, hydrogen bonds, and π-π electron donor-acceptor (EDA) interactions were discussed to explain the enhanced adsorption behavior of BPAF on AC-AB with CTAB. The findings verified the effectiveness of AC-AB for the removal of BPAF from wastewater and its high stability within five regeneration cycles. Copyright © 2017 Elsevier Inc. All rights reserved.

Electric tempest in a teacup: The tea leaf analogy to microfluidic blood plasma separation

NASA Astrophysics Data System (ADS)

Yeo, Leslie Y.; Friend, James R.; Arifin, Dian R.

2006-09-01

In a similar fashion to Einstein's tea leaf paradox, the rotational liquid flow induced by ionic wind above a liquid surface can trap suspended microparticles by a helical motion, spinning them down towards a bottom stagnation point. The motion is similar to Batchelor [Q. J. Mech. Appl. Math. 4, 29 (1951)] flows occurring between stationary and rotating disks and arises due to a combination of the primary azimuthal and secondary bulk meridional recirculation that produces a centrifugal and enhanced inward radial force near the chamber bottom. The technology is thus useful for microfluidic particle trapping/concentration; the authors demonstrate its potential for rapid erythrocyte/blood plasma separation for miniaturized medical diagnostic kits.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles.

PubMed

Hu, Tianmu; Qahtan, Anwar Saeed Ahmed; Lei, Lei; Lei, Zhixin; Zhao, Dapeng; Nie, Hemin

2018-03-01

In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p  > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.

Comparative study on the in vitro effects of Pseudomonas aeruginosa and seaweed alginates on human gut microbiota

PubMed Central

Bai, Shaofeng; Chen, Huahai; Zhu, Liying; Liu, Wei; Yu, Hongwei D.; Wang, Xin; Yin, Yeshi

2017-01-01

Alginates pertain to organic polysaccharides that have been extensively used in food- and medicine-related industries. The present study obtained alginates from an alginate overproducing Pseudomonas aeruginosa PAO1 mutant by screening transposon mutagenesis libraries. The interaction between bacterial and seaweed alginates and gut microbiota were further studied by using an in vitro batch fermentation system. Thin-layer chromatography (TLC) analysis indicated that both bacterial and seaweed alginates can be completely degraded by fecal bacteria isolated from study volunteers, indicating that a minor structural difference between bacterial and seaweed alginates (O-acetylation and lack of G-G blocks) didn’t affect the digestion of alginates by human microbiota. Although, the digestion of bacterial and seaweed alginates was attributed to different Bacteroides xylanisolvens strains, they harbored similar alginate lyase genes. Genus Bacteroides with alginate-degrading capability were enriched in growth medium containing bacterial or seaweed alginates after in vitro fermentation. Short-chain fatty acid (SCFA) production in both bacterial and seaweed alginates was also comparable, but was significantly higher than the same medium using starch. In summary, the present study has isolated an alginate-overproducing P. aeruginosa mutant strain. Both seaweed and bacterial alginates were degraded by human gut microbiota, and their regulatory function on gut microbiota was similar. PMID:28170428

Comparative study on the in vitro effects of Pseudomonas aeruginosa and seaweed alginates on human gut microbiota.

PubMed

Bai, Shaofeng; Chen, Huahai; Zhu, Liying; Liu, Wei; Yu, Hongwei D; Wang, Xin; Yin, Yeshi

2017-01-01

Alginates pertain to organic polysaccharides that have been extensively used in food- and medicine-related industries. The present study obtained alginates from an alginate overproducing Pseudomonas aeruginosa PAO1 mutant by screening transposon mutagenesis libraries. The interaction between bacterial and seaweed alginates and gut microbiota were further studied by using an in vitro batch fermentation system. Thin-layer chromatography (TLC) analysis indicated that both bacterial and seaweed alginates can be completely degraded by fecal bacteria isolated from study volunteers, indicating that a minor structural difference between bacterial and seaweed alginates (O-acetylation and lack of G-G blocks) didn't affect the digestion of alginates by human microbiota. Although, the digestion of bacterial and seaweed alginates was attributed to different Bacteroides xylanisolvens strains, they harbored similar alginate lyase genes. Genus Bacteroides with alginate-degrading capability were enriched in growth medium containing bacterial or seaweed alginates after in vitro fermentation. Short-chain fatty acid (SCFA) production in both bacterial and seaweed alginates was also comparable, but was significantly higher than the same medium using starch. In summary, the present study has isolated an alginate-overproducing P. aeruginosa mutant strain. Both seaweed and bacterial alginates were degraded by human gut microbiota, and their regulatory function on gut microbiota was similar.

Identification of enzymes responsible for extracellular alginate depolymerization and alginate metabolism in Vibrio algivorus.

PubMed

Doi, Hidetaka; Tokura, Yuriko; Mori, Yukiko; Mori, Kenichi; Asakura, Yoko; Usuda, Yoshihiro; Fukuda, Hiroo; Chinen, Akito

2017-02-01

Alginate is a marine non-food-competing polysaccharide that has potential applications in biorefinery. Owing to its large size (molecular weight >300,000 Da), alginate cannot pass through the bacterial cell membrane. Therefore, bacteria that utilize alginate are presumed to have an enzyme that degrades extracellular alginate. Recently, Vibrio algivorus sp. SA2 T was identified as a novel alginate-decomposing and alginate-utilizing species. However, little is known about the mechanism of alginate degradation and metabolism in this species. To address this issue, we screened the V. algivorus genomic DNA library for genes encoding polysaccharide-decomposing enzymes using a novel double-layer plate screening method and identified alyB as a candidate. Most identified alginate-decomposing enzymes (i.e., alginate lyases) must be concentrated and purified before extracellular alginate depolymerization. AlyB of V. algivorus heterologously expressed in Escherichia coli depolymerized extracellular alginate without requiring concentration or purification. We found seven homologues in the V. algivorus genome (alyB, alyD, oalA, oalB, oalC, dehR, and toaA) that are thought to encode enzymes responsible for alginate transport and metabolism. Introducing these genes into E. coli enabled the cells to assimilate soluble alginate depolymerized by V. algivorus AlyB as the sole carbon source. The alginate was bioconverted into L-lysine (43.3 mg/l) in E. coli strain AJIK01. These findings demonstrate a simple and novel screening method for identifying polysaccharide-degrading enzymes in bacteria and provide a simple alginate biocatalyst and fermentation system with potential applications in industrial biorefinery.

Hydrogel Actuation by Electric Field Driven Effects

NASA Astrophysics Data System (ADS)

Morales, Daniel Humphrey

Hydrogels are networks of crosslinked, hydrophilic polymers capable of absorbing and releasing large amounts of water while maintaining their structural integrity. Polyelectrolyte hydrogels are a subset of hydrogels that contain ionizable moieties, which render the network sensitive to the pH and the ionic strength of the media and provide mobile counterions, which impart conductivity. These networks are part of a class of "smart" material systems that can sense and adjust their shape in response to the external environment. Hence, the ability to program and modulate hydrogel shape change has great potential for novel biomaterial and soft robotics applications. We utilized electric field driven effects to manipulate the interaction of ions within polyelectrolyte hydrogels in order to induce controlled deformation and patterning. Additionally, electric fields can be used to promote the interactions of separate gel networks, as modular components, and particle assemblies within gel networks to develop new types of soft composite systems. First, we present and analyze a walking gel actuator comprised of cationic and anionic gel legs attached by electric field-promoted polyion complexation. We characterize the electro-osmotic response of the hydrogels as a function of charge density and external salt concentration. The gel walkers achieve unidirectional motion on flat elastomer substrates and exemplify a simple way to move and manipulate soft matter devices in aqueous solutions. An 'ionoprinting' technique is presented with the capability to topographically structure and actuate hydrated gels in two and three dimensions by locally patterning ions induced by electric fields. The bound charges change the local mechanical properties of the gel to induce relief patterns and evoke localized stress, causing rapid folding in air. The ionically patterned hydrogels exhibit programmable temporal and spatial shape transitions which can be tuned by the duration and/or strength of the applied electric field. We extend the use of ionoprinting to develop multi-responsive bilayer gel systems capable of more complex shape transformation. The localized crosslinked regions determine the bending axis as the gel responds to the external environment. The bending can be tuned to reverse direction isothermally by changing the solvent quality or by changing the temperature at a fixed concentration. The multi-responsive behavior is caused by the volume transitions of a non-ionic, thermos-sensitive hydrogel coupled with a superabsorbent ionic hydrogel. Lastly, electric field driven microparticle assembly, using dielectrophoretic (DEP) forces, organized colloidal microparticles within a hydrogel matrix. The use of DEP forces enables rapid, efficient and precise control over the colloidal distribution. The resulting supracolloidal endoskeleton structures impart directional bending as the hydrogel shrinks. We compare the ordered particles structures to random particle distributions in affecting the hydrogel sheet bending response. This study demonstrates a universal technique for imparting directional properties in hydrogels towards new generations of hybrid soft materials.

Autoinducer Sensing Microarrays by Reporter Bacteria Encapsulated in Hybrid Supramolecular-Polysaccharide Hydrogels.

PubMed

Li, Ping; Dou, Xiaoqiu; Müller, Mareike; Feng, Chuanliang; Chang, Matthew Wook; Frettlöh, Martin; Schönherr, Holger

2017-11-01

A generally applicable strategy to obtain mechanically robust hydrogels for the incorporation and containment of functional reporter bacteria for the microarray and microparticle-based detection and signaling of N-acyl homoserine lactone autoinducers (3OC 12 HSL) at relevant concentrations is reported. For reinforcing hydrogels of 1,4-bi(phenylalanine-diglycol)-benzene (PDB), a hybrid hydrogel is formed by the combination of PDB self-assembly with Ca 2+ mediated alginate crosslinking. The different assembly mechanisms are shown not to interfere with each other and despite the more than four-fold increased moduli of the hydrogels, diffusion of autoinducers into the gels remains efficient and Escherichia coli pLuxR-green fluorescent protein (GFP) reporter bacteria are proliferating. Templating affords reporter bacteria-loaded hydrogels with controllable shape and size. Upon exposure to 3OC 12 HSL, the embedded bacteria exhibit an up to 12 ± 3 times increase in fluorescence intensity due to autoinducer-triggered GFP expression. This approach can serve as a potentially generally applicable strategy to sensitively detect bacteria via their secreted autoinducers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

21 CFR 184.1610 - Potassium alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Potassium alginate. 184.1610 Section 184.1610 Food... GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown algae. Potassium alginate is...

21 CFR 184.1724 - Sodium alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium alginate. 184.1724 Section 184.1724 Food... GRAS § 184.1724 Sodium alginate. (a) Sodium alginate (CAS Reg. No. 9005-38-3) is the sodium salt of alginic acid, a natural polyuronide constituent of certain brown algae. Sodium alginate is prepared by the...

21 CFR 184.1724 - Sodium alginate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium alginate. 184.1724 Section 184.1724 Food and... Substances Affirmed as GRAS § 184.1724 Sodium alginate. (a) Sodium alginate (CAS Reg. No. 9005-38-3) is the sodium salt of alginic acid, a natural polyuronide constituent of certain brown algae. Sodium alginate is...

21 CFR 184.1187 - Calcium alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium alginate. 184.1187 Section 184.1187 Food... GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005-35-0) is the calcium salt of alginic acid, a natural polyuronide constituent of certain brown algae. Calcium alginate is prepared by...

Magnesium Oxide Nanoparticles Reinforced Electrospun Alginate-Based Nanofibrous Scaffolds with Improved Physical Properties

PubMed Central

Mantilaka, M. M. M. G. P. G.; Goh, K. L.; Ratnayake, S. P.; Amaratunga, G. A. J.; de Silva, K. M. Nalin

2017-01-01

Mechanically robust alginate-based nanofibrous scaffolds were successfully fabricated by electrospinning method to mimic the natural extracellular matrix structure which benefits development and regeneration of tissues. Alginate-based nanofibres were electrospun from an alginate/poly(vinyl alcohol) (PVA) polyelectrolyte complex. SEM images revealed the spinnability of the complex composite nanofibrous scaffolds, showing randomly oriented, ultrafine, and virtually defects-free alginate-based/MgO nanofibrous scaffolds. Here, it is shown that an alginate/PVA complex scaffold, blended with near-spherical MgO nanoparticles (⌀ 45 nm) at a predetermined concentration (10% (w/w)), is electrospinnable to produce a complex composite nanofibrous scaffold with enhanced mechanical stability. For the comparison purpose, chemically cross-linked electrospun alginate-based scaffolds were also fabricated. Tensile test to rupture revealed the significant differences in the tensile strength and elastic modulus among the alginate scaffolds, alginate/MgO scaffolds, and cross-linked alginate scaffolds (P < 0.05). In contrast to cross-linked alginate scaffolds, alginate/MgO scaffolds yielded the highest tensile strength and elastic modulus while preserving the interfibre porosity of the scaffolds. According to the thermogravimetric analysis, MgO reinforced alginate nanofibrous scaffolds exhibited improved thermal stability. These novel alginate-based/MgO scaffolds are economical and versatile and may be further optimised for use as extracellular matrix substitutes for repair and regeneration of tissues. PMID:28694826

Falsirhodobacter sp. alg1 Harbors Single Homologs of Endo and Exo-Type Alginate Lyases Efficient for Alginate Depolymerization

PubMed Central

Takahashi, Mami; Tanaka, Reiji; Miyake, Hideo; Shibata, Toshiyuki; Chow, Seinen; Kuroda, Kouichi; Ueda, Mitsuyoshi; Takeyama, Haruko

2016-01-01

Alginate-degrading bacteria play an important role in alginate degradation by harboring highly efficient and unique alginolytic genes. Although the general mechanism for alginate degradation by these bacteria is fairly understood, much is still required to fully exploit them. Here, we report the isolation of a novel strain, Falsirhodobacter sp. alg1, the first report for an alginate-degrading bacterium from the family Rhodobacteraceae. Genome sequencing reveals that strain alg1 harbors a primary alginate degradation pathway with only single homologs of an endo- and exo-type alginate lyase, AlyFRA and AlyFRB, which is uncommon among such bacteria. Subsequent functional analysis showed that both enzymes were extremely efficient to depolymerize alginate suggesting evolutionary interests in the acquirement of these enzymes. The exo-type alginate lyase, AlyFRB in particular could depolymerize alginate without producing intermediate products making it a highly efficient enzyme for the production of 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEH). Based on our findings, we believe that the discovery of Falsirhodobacter sp. alg1 and its alginolytic genes hints at the potentiality of a more diverse and unique population of alginate-degrading bacteria. PMID:27176711

Differential procoagulant activity of microparticles derived from monocytes, granulocytes, platelets and endothelial cells: impact of active tissue factor.

PubMed

Shustova, Olga N; Antonova, Olga A; Golubeva, Nina V; Khaspekova, Svetlana G; Yakushkin, Vladimir V; Aksuk, Svetlana A; Alchinova, Irina B; Karganov, Mikhail Y; Mazurov, Alexey V

2017-07-01

: Microparticles released by activated/apoptotic cells exhibit coagulation activity as they express phosphatidylserine and some of them - tissue factor. We compared procoagulant properties of microparticles from monocytes, granulocytes, platelets and endothelial cells and assessed the impact of tissue factor in observed differences. Microparticles were sedimented (20 000g, 30 min) from the supernatants of activated monocytes, monocytic THP-1 cells, granulocytes, platelets and endothelial cells. Coagulation activity of microparticles was examined using plasma recalcification assay. The size of microparticles was evaluated by dynamic light scattering. Tissue factor activity was measured by its ability to activate factor X. All microparticles significantly accelerated plasma coagulation with the shortest lag times for microparticles derived from monocytes, intermediate - for microparticles from THP-1 cells and endothelial cells, and the longest - for microparticles from granulocytes and platelets. Average diameters of microparticles ranged within 400-600 nm. The largest microparticles were produced by endothelial cells and granulocytes, smaller - by monocytes, and the smallest - by THP-1 cells and platelets. The highest tissue factor activity was detected in microparticles from monocytes, lower activity - in microparticles from endothelial cells and THP-1 cells, and no activity - in microparticles from platelets and granulocytes. Anti-tissue factor antibodies extended coagulation lag times for microparticles from monocytes, endothelial cells and THP-1 cells and equalized them with those for microparticles from platelets and granulocytes. Higher coagulation activity of microparticles from monocytes, THP-1 cells and endothelial cells in comparison with microparticles from platelets and granulocytes is determined mainly by the presence of active tissue factor.

Preparation of highly stable zeolite-alginate foam composite for strontium(90Sr) removal from seawater and evaluation of Sr adsorption performance.

PubMed

Hong, Hye-Jin; Kim, Byoung-Gyu; Ryu, Jungho; Park, In-Su; Chung, Kang-Sup; Lee, Sang Moon; Lee, Jin-Bae; Jeong, Hyeon Su; Kim, Hyunchul; Ryu, Taegong

2018-01-01

Alginate bead is a promising strontium (Sr) adsorbent in seawater, but highly concentrated Na ions caused over-swelling and damaged the hydrogel bead. To improve the mechanical stability of alginate bead, flexible foam-type zeolite-alginate composite was synthesized and Sr adsorption performance was evaluated in seawater; 1-10% zeolite immobilized alginate foams were prepared by freeze-dry technique. Immobilization of zeolite into alginate foam converted macro-pores to meso-pores which lead to more compact structure. It resulted in less swollen composite in seawater medium and exhibited highly improved mechanical stability compared with alginate bead. Besides, Sr adsorption efficiency and selectivity were enhanced by immobilization of zeolite in alginate foam due to the increase of Sr binding sites (zeolite). In particular, Sr selectivity against Na was highly improved. The 10% zeolite-alginate foam exhibited a higher log K d of 3.3, while the pure alginate foam exhibited 2.7 in the presence of 0.1 M Na. Finally, in the real seawater, the 10% zeolite-alginate foam exhibited 1.5 times higher Sr adsorption efficiency than the pure alginate foam. This result reveals that zeolite-alginate foam composite is appropriate material for Sr removal in seawater due to its swelling resistance as well as improved Sr adsorption performance in complex media. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of storage duration on the setting time of type 1 alginate impression material

NASA Astrophysics Data System (ADS)

Rahmadina, A.; Triaminingsih, S.; Irawan, B.

2017-08-01

Alginate is one of the most commonly used dental impression materials; however, its setting time is subject to change depending on storage conditions and duration. This creates problems because consumer carelessness can affect alginate shelf life and quality. In the present study, the setting times of two groups of type I alginate with different expiry dates was tested. The first group consisted of 11 alginate specimens that had not yet passed the expiry date, and the second group consisted of alginates that had passed the expiry date. The alginate powder was mixed with distilled water, poured into a metal ring, and tested with a polished rod of poly-methyl methacrylate. Statistical analysis showed a significant difference (p<0.05) between the setting times of the alginate that had not passed the expiry date (157 ± 3 seconds) and alginate that had passed the expiry date (144 ± 2 seconds). These findings indicate that storage duration can affect alginate setting time.

Development and Characterization of Mechanically Robust, 3D-Printable Photopolymers

NASA Astrophysics Data System (ADS)

Sycks, Dalton George

3D printing has seen an explosion of interest and growth in recent years, especially within the biomedical space. Prized for its efficiency, ability to produce complex geometries, and facile material processing, additive manufacturing is rapidly being used to create medical devices ranging from orthopedic implants to tissue scaffolds. However, 3D printing is currently limited to a select few material choices, especially when one considers soft tissue replacement or augmentation. To this end, my research focuses on developing material systems that are simultaneously 1) 3D printable, 2) biocompatible, and 3) mechanically robust with properties appropriate for soft-tissue replacement or augmentation applications. Two systems were developed toward this goal: an interpenetrating network (IPN) hydrogel consisting of covalently crosslinked poly (ethylene glycol) diacrylate (PEGDA) and ionically crosslinked brown sodium alginate, and semi-crystalline thiol-ene photopolymers containing spiroacetal molecules in the polymer main-chain backbone. In addition to successfully being incorporated into existing 3D printing systems (extrusion-deposition for the PEGDA-alginate hydrogel and digital light processing for the thiol-ene polymers) both systems exhibited biocompatibility and superior thermomechanical properties such as tensile modulus, failure strain, and toughness. This work offers two fully-developed, novel polymer platforms with outstanding performance; further, structure-property relationships are highlighted and discussed on a molecular and morphological level to provide material insights that are useful to researchers and engineers in the design of highly tuned and mechanically robust polymers.

Fluoride loaded polymeric nanoparticles for dental delivery.

PubMed

Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

2017-06-15

The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

Bone Morphogenetic Protein-2 Promotes Human Mesenchymal Stem Cell Survival and Resultant Bone Formation When Entrapped in Photocrosslinked Alginate Hydrogels.

PubMed

Ho, Steve S; Vollmer, Nina L; Refaat, Motasem I; Jeon, Oju; Alsberg, Eben; Lee, Mark A; Leach, J Kent

2016-10-01

There is a substantial need to prolong cell persistence and enhance functionality in situ to enhance cell-based tissue repair. Bone morphogenetic protein-2 (BMP-2) is often used at high concentrations for osteogenic differentiation of mesenchymal stem cells (MSCs) but can induce apoptosis. Biomaterials facilitate the delivery of lower doses of BMP-2, reducing side effects and localizing materials at target sites. Photocrosslinked alginate hydrogels (PAHs) can deliver osteogenic materials to irregular-sized bone defects, providing improved control over material degradation compared to ionically cross-linked hydrogels. It is hypothesized that the delivery of MSCs and BMP-2 from a PAH increases cell persistence by reducing apoptosis, while promoting osteogenic differentiation and enhancing bone formation compared to MSCs in PAHs without BMP-2. BMP-2 significantly decreases apoptosis and enhances survival of photoencapsulated MSCs, while simultaneously promoting osteogenic differentiation in vitro. Bioluminescence imaging reveals increased MSC survival when implanted in BMP-2 PAHs. Bone defects treated with MSCs in BMP-2 PAHs demonstrate 100% union as early as 8 weeks and significantly higher bone volumes at 12 weeks, while defects with MSC-entrapped PAHs alone do not fully bridge. This study demonstrates that transplantation of MSCs with BMP-2 in PAHs achieves robust bone healing, providing a promising platform for bone repair. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physicochemical properties of marine collagen-alginate biomaterial

NASA Astrophysics Data System (ADS)

Soon, K. S.; Hii, S. L.; Wong, C. L.; Leong, L. K.; Woo, K. K.

2017-12-01

Collagen base biomaterials are widely applied in the field of tissue engineering. However, these fibrous proteins in animal connective tissues are insufficient to fulfill the mechanical properties for such applications. Therefore, alginate as a natural polysaccharide was incorporated. In this study, Smooth wolf herring skins was collected from the local fish ball processing industry for collagen extraction using acid solubilisation method. On the other hand, alginate from brown seaweed (Sargassum polycystum) was extracted with calcium carbonate at 50 °C. The composite films of different collagen and alginate ratio were prepared by lyophilisation with pure collagen film as control. The effects of alginate on swelling behaviour, porosity, collagenase degradation and tensile strength of the composite films were investigated. Swelling behaviour increased with alginate content, 50 % alginate film achieved 1254.75 % swelling after 24 h. All composite films achieved more than 80 % porosity except the film with 80 % collagen (65.41 %). Porosity was highest in 100 % alginate (94.30 %). Highest tensile strength (1585.87 kPa) and young modulus (27.05 MPa) was found in 50 % alginate film. In addition, resistance to collagenase degradation was improved with alginate content, lowest degradation rate was determined in 80 % alginate film. Results indicated alginate is efficient in improving some mechanical properties of the composite film.

Raman probing of molecular interactions of alginate biopolymers with cells

NASA Astrophysics Data System (ADS)

Chourpa, Igor; Carpentier, Philippe; Maingault, Philippe; Fetissoff, Franck; Dubois, Pierre

2000-05-01

The biological polymers extracted from brown algae, alginates, are novel materials in biotechnology and biomedicine. Their ability to form viscous gels is used to immobilize or encapsulate yeast, enzymes, living cells and drugs. Calcium-alginate fibers are extensively used in wound dressings since exhibit antihaemostatic and healing properties. The problem with alginate-made dressings in surgery is their slow biodegradability: if entrapped within tissues, they can induce a local cellular recruitment with an inflammatory response contemporaneous to the resorption phase. In part, this problem is a consequence of poor solubility of the calcium alginates in water. Although calcium alginate fibers can exchange calcium ions with sodium ions from the wound exudate to create a calcium/sodium alginate fibers, the residual alginates are thought to be not totally degradable in vivo. Rapid and non- destructive characterization of series of the crude alginates and calcium alginate fibers has been performed using Raman spectroscopy with near IR excitation. Study of structural organization of the polymeric chains within calcium alginate fibers have been previously reported as made by confocal Raman multispectral imaging (CRMSI) in visible. Here, the Raman approach has been used to monitor the ion exchange reactions for different types of alginates and their salts in vitro. For in vivo evaluation, histological sections of alginate-treated rat tissue have been analyzed by light microscopy and CRMSI. The in vitro Raman modeling and the histochemical mapping were a necessary precursor for application of the Raman microprobe to follow in a non-invasive way the alginate-cell molecular interactions in rat tissue.

Microparticles Engineered to Highly Express Peroxisome Proliferator-Activated Receptor-γ Decreased Inflammatory Mediator Production and Increased Adhesion of Recipient Monocytes

PubMed Central

Sahler, Julie; Woeller, Collynn F.; Phipps, Richard P.

2014-01-01

Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ). In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles also changed monocyte mRNA levels of several genes including those under PPARγ control. Overall, the delivery of PPARγ from microparticles to human monocytes influenced gene expression, decreased inflammatory mediator production and increased monocyte adherence. These results support the concept that the composition of blood microparticles has a profound impact on the function of cells with which they interact, and likely plays a role in vascular inflammation. PMID:25426628

Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

PubMed

Sahler, Julie; Woeller, Collynn F; Phipps, Richard P

2014-01-01

Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ). In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles also changed monocyte mRNA levels of several genes including those under PPARγ control. Overall, the delivery of PPARγ from microparticles to human monocytes influenced gene expression, decreased inflammatory mediator production and increased monocyte adherence. These results support the concept that the composition of blood microparticles has a profound impact on the function of cells with which they interact, and likely plays a role in vascular inflammation.

Ca:Mg:Zn:CO3 and Ca:Mg:CO3-tri- and bi-elemental carbonate microparticles for novel injectable self-gelling hydrogel-microparticle composites for tissue regeneration.

PubMed

Douglas, Timothy E L; Sobczyk, Katarzyna; Łapa, Agata; Włodarczyk, Katarzyna; Brackman, Gilles; Vidiasheva, Irina; Reczyńska, Katarzyna; Pietryga, Krzysztof; Schaubroeck, David; Bliznuk, Vitaliy; Voort, Pascal Van Der; Declercq, Heidi A; Bulcke, Jan Van den; Samal, Sangram Keshari; Khalenkow, Dmitry; Parakhonskiy, Bogdan V; Van Acker, Joris; Coenye, Tom; Lewandowska-Szumieł, Małgorzata; Pamuła, Elżbieta; Skirtach, Andre G

2017-03-24

Injectable composites for tissue regeneration can be developed by dispersion of inorganic microparticles and cells in a hydrogel phase. In this study, multifunctional carbonate microparticles containing different amounts of calcium, magnesium and zinc were mixed with solutions of gellan gum (GG), an anionic polysaccharide, to form injectable hydrogel-microparticle composites, containing Zn, Ca and Mg. Zn and Ca were incorporated into microparticle preparations to a greater extent than Mg. Microparticle groups were heterogeneous and contained microparticles of differing shape and elemental composition. Zn-rich microparticles were 'star shaped' and appeared to consist of small crystallites, while Zn-poor, Ca- and Mg-rich microparticles were irregular in shape and appeared to contain lager crystallites. Zn-free microparticle groups exhibited the best cytocompatibility and, unexpectedly, Zn-free composites showed the highest antibacterial activity towards methicilin-resistant Staphylococcus aureus. Composites containing Zn-free microparticles were cytocompatible and therefore appear most suitable for applications as an injectable biomaterial. This study proves the principle of creating bi- and tri-elemental microparticles to induce the gelation of GG to create injectable hydrogel-microparticle composites.

21 CFR 184.1610 - Potassium alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Potassium alginate. 184.1610 Section 184.1610 Food... Specific Substances Affirmed as GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown...

21 CFR 184.1610 - Potassium alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Potassium alginate. 184.1610 Section 184.1610 Food... Specific Substances Affirmed as GRAS § 184.1610 Potassium alginate. (a) Potassium alginate (CAS Reg. No. 9005-36-1) is the potassium salt of alginic acid, a natural polyuronide constituent of certain brown...

Properties of alginate fiber spun-dyed with fluorescent pigment dispersion.

PubMed

Wang, Ping; Tawiah, Benjamin; Tian, Anli; Wang, Chunxia; Zhang, Liping; Fu, Shaohai

2015-03-15

Spun-dyed alginate fiber was prepared by the spun-dyeing method with the mixture of fluorescent pigment dispersion and sodium alginate fiber spinning solution, and its properties were characterized by SEM, TGA, DSC, and XRD. The results indicate that fluorescent pigment dispersion prepared with esterified poly (styrene-alt maleic acid) had excellent compatibility with sodium alginate fiber spinning solution, and small amount of fluorescent pigment could reduce the viscosity of spun-dyed spinning solutions. SEM photo of spun-dyed alginate fiber indicated that fewer pigment particles deposited on its surface. TGA, DSC, and XRD results suggested that thermal properties and crystal phase of spun-dyed alginate fibers had slight changes compared to the original alginate fibers. The fluorescence intensity of spun-dyed alginate fiber reached its maximum when the content of fluorescent pigment was 4%. The spun-dyed alginate fiber showed excellent rubbing and washing fastness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

PubMed Central

Mhanna, Rami; Kashyap, Aditya; Palazzolo, Gemma; Vallmajo-Martin, Queralt; Becher, Jana; Möller, Stephanie; Schnabelrauch, Matthias

2014-01-01

The loss of expression of chondrogenic markers during monolayer expansion remains a stumbling block for cell-based treatment of cartilage lesions. Here, we introduce sulfated alginate hydrogels as a cartilage biomimetic biomaterial that induces cell proliferation while maintaining the chondrogenic phenotype of encapsulated chondrocytes. Hydroxyl groups of alginate were converted to sulfates by incubation with sulfur trioxide–pyridine complex (SO3/pyridine), yielding a sulfated material cross-linkable with calcium chloride. Passage 3 bovine chondrocytes were encapsulated in alginate and alginate sulfate hydrogels for up to 35 days. Cell proliferation was five-fold higher in alginate sulfate compared with alginate (p=0.038). Blocking beta1 integrins in chondrocytes within alginate sulfate hydrogels significantly inhibited proliferation (p=0.002). Sulfated alginate increased the RhoA activity of chondrocytes compared with unmodified alginate, an increase that was blocked by β1 blocking antibodies (p=0.017). Expression and synthesis of type II collagen, type I collagen, and proteoglycan was not significantly affected by the encapsulation material evidenced by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Alginate sulfate constructs showed an opaque appearance in culture, whereas the unmodified alginate samples remained translucent. In conclusion, alginate sulfate provides a three dimensional microenvironment that promotes both chondrocyte proliferation and maintenance of the chondrogenic phenotype and represents an important advance for chondrocyte-based cartilage repair therapies providing a material in which cell expansion can be done in situ. PMID:24320935

Elemental maps in human allantochorial placental vessels cells: 1. High K + and acetylcholine effects

NASA Astrophysics Data System (ADS)

Michelet-Habchi, C.; Barberet, Ph.; Dutta, R. K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph.

2003-09-01

Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K + and Ca 2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K + channels, K Ca) and of high concentration of K + (which blocks the voltage-sensitive K + channels, K df). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K + medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K + medium, a significant increase in Cl and K concentration. These results indicated the importance of K df, K Ca and K ATP channels in the regulation of K + intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.

Encapsulating anthocyanins from Hibiscus sabdariffa L. calyces by ionic gelation: Pigment stability during storage of microparticles.

PubMed

de Moura, Sílvia C S R; Berling, Carolina L; Germer, Sílvia P M; Alvim, Izabela D; Hubinger, Míriam D

2018-02-15

Hibiscus extract (HE) has a strong antioxidant activity and high anthocyanin content; it can be used as a natural pigment, also adding potential health benefits. The objective of this work was the microencapsulation of HE anthocyanin by ionic gelation (IG) using two techniques: dripping-extrusion and atomization, both by means of a double emulsion (HE/rapseed oil/pectin) and a cross-linked solution (CaCl 2 ). Particles (77-83% moisture content) were conditioned in acidified solution at 5, 15 and 25°C, absence of light, and evaluated for anthocyanins and color for 50-days. The median diameter (D 50 ) of the particles ranged from 78 to 1100μm and encapsulation efficiency ranged from 67.9 to 93.9%. The encapsulation caused higher temperature stability compared with the free extract. The half-life (t 1/2 ) values of the particles ranged from 7 (25°C) to 180days (5°C) for anthocyanins and from 25 (25°C) to 462days (5°C) for Chroma value. The IG increased the stability of HE anthocyanin. Both the dripping-extrusion and the atomization have shown to be feasible techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

PubMed Central

Lacroix, Romaric; Plawinski, Laurent; Robert, Stéphane; Doeuvre, Loïc; Sabatier, Florence; Martinez de Lizarrondo, Sara; Mezzapesa, Anna; Anfosso, Francine; Leroyer, Aurelie S.; Poullin, Pascale; Jourde, Noémie; Njock, Makon-Sébastien; Boulanger, Chantal M.; Anglés-Cano, Eduardo; Dignat-George, Françoise

2012-01-01

Background We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and Methods Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. Results Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. Conclusions Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium. PMID:22733025

21 CFR 184.1724 - Sodium alginate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium alginate. 184.1724 Section 184.1724 Food... Specific Substances Affirmed as GRAS § 184.1724 Sodium alginate. (a) Sodium alginate (CAS Reg. No. 9005-38-3) is the sodium salt of alginic acid, a natural polyuronide constituent of certain brown algae...

21 CFR 184.1724 - Sodium alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium alginate. 184.1724 Section 184.1724 Food... Specific Substances Affirmed as GRAS § 184.1724 Sodium alginate. (a) Sodium alginate (CAS Reg. No. 9005-38-3) is the sodium salt of alginic acid, a natural polyuronide constituent of certain brown algae...

21 CFR 184.1724 - Sodium alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium alginate. 184.1724 Section 184.1724 Food... Specific Substances Affirmed as GRAS § 184.1724 Sodium alginate. (a) Sodium alginate (CAS Reg. No. 9005-38-3) is the sodium salt of alginic acid, a natural polyuronide constituent of certain brown algae...

21 CFR 184.1187 - Calcium alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium alginate. 184.1187 Section 184.1187 Food... Specific Substances Affirmed as GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005-35-0) is the calcium salt of alginic acid, a natural polyuronide constituent of certain brown algae...

21 CFR 184.1187 - Calcium alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium alginate. 184.1187 Section 184.1187 Food... Specific Substances Affirmed as GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005-35-0) is the calcium salt of alginic acid, a natural polyuronide constituent of certain brown algae...

Mammalian Cell Encapsulation in Alginate Beads Using a Simple Stirred Vessel.

PubMed

Hoesli, Corinne A; Kiang, Roger L J; Raghuram, Kamini; Pedroza, René G; Markwick, Karen E; Colantuoni, Antonio M R; Piret, James M

2017-06-29

Cell encapsulation in alginate beads has been used for immobilized cell culture in vitro as well as for immunoisolation in vivo. Pancreatic islet encapsulation has been studied extensively as a means to increase islet survival in allogeneic or xenogeneic transplants. Alginate encapsulation is commonly achieved by nozzle extrusion and external gelation. Using this method, cell-containing alginate droplets formed at the tip of nozzles fall into a solution containing divalent cations that cause ionotropic alginate gelation as they diffuse into the droplets. The requirement for droplet formation at the nozzle tip limits the volumetric throughput and alginate concentration that can be achieved. This video describes a scalable emulsification method to encapsulate mammalian cells in 0.5% to 10% alginate with 70% to 90% cell survival. By this alternative method, alginate droplets containing cells and calcium carbonate are emulsified in mineral oil, followed by a decrease in pH leading to internal calcium release and ionotropic alginate gelation. The current method allows the production of alginate beads within 20 min of emulsification. The equipment required for the encapsulation step consists in simple stirred vessels available to most laboratories.

Effect of gamma radiation on the physico-chemical properties of alginate-based films and beads

NASA Astrophysics Data System (ADS)

Huq, Tanzina; Khan, Avik; Dussault, Dominic; Salmieri, Stephane; Khan, Ruhul A.; Lacroix, Monique

2012-08-01

Alginate solution (3%, w/v) was prepared using deionized water from its powder. Then the solution was exposed to gamma radiation (0.1-25 kGy). The alginate films were prepared by solution casting. It was found that gamma radiation has strong effect on alginate solution. At low doses, mechanical strength of the alginate films improved but after 5 kGy dose, the strength started to decrease. The mechanism of alginate radiolysis in aqueous solution is discussed. Film formation was not possible from alginate solution at doses >5 kGy. The mechanical properties such as puncture strength (PS), puncture deformation (PD), viscoelasticity (Y) coefficient of the un-irradiated films were investigated. The values of PS, PD and Y coefficient of the films were 333 N/mm, 3.20 mm and 27%, respectively. Alginate beads were prepared from 3% alginate solution (w/v) by ionotropic gelation method in 5% CaCl2 solution. The rate of gel swelling improved in irradiated alginate-based beads at low doses (up to 0.5 kGy).

Optimization of culturing condition and medium composition for the production of alginate lyase by a marine Vibrio sp. YKW-34

NASA Astrophysics Data System (ADS)

Fu, Xiaoting; Lin, Hong; Kim, Sang Moo

2008-02-01

Carbohydrases secreted by marine Vibrio sp. YKW-34 with strong Laminaria cell wall degrading ability were screened, and among them alginate lyase was found to be dominant. The effects of medium composition and culturing condition on the production of alginate lyase by marine Vibrio sp. YKW-34 in flask were investigated in this study. In the culture medium of marine broth, no alginate lyase was produced. The activity of the alginate lyase, after being induced, reached 5 UmL-1. The best inoculum volume and inoculum age were 10% and 12 h, respectively. The optimal temperature for alginate lyase production was 25°C. The fermentation medium was composed of 0.5% of Laminaria powder and 0.2% of KNO3 with an initial acidity of pH 8.0. Alginate could induce alginate lyase production but not as efficiently as Laminaria powder did. The addition of fucoidan, cellulose and glucose had negative effect on the alginate lyase production. Other kinds of nitrogen sources, such as yeast extract, beef extract and peptone, had positive effect on the growth of the microorganism and negative effect on alginate lyase production. In addition, the time course of alginate lyase production under the optimized condition was described. The optimal harvest time was 48 h.

Self-disinfecting Alginate vs Conventional Alginate: Effect on Surface Hardness of Gypsum Cast-An in vitro Study.

PubMed

Madhavan, Ranjith; George, Navia; Thummala, Niharika R; Ravi, S V; Nagpal, Ajay

2017-11-01

For the construction of any dental prosthesis, accurate impressions are necessary. Hence, we undertook the present study to evaluate and compare the surface hardness of gypsum casts poured from impressions made using conventional alginate and self-disinfecting alginate. A total of 30 impressions of stainless steel die were made, out of which 15 impressions were made with conventional alginate and 15 were made with self-disinfecting alginate and poured using Type III dental stone. Thirty stone specimens were subjected for hardness testing. Data were analyzed using independent samples t-test to compare the mean surface hardness. Difference in surface hardness was statistically insignificant (p > 0.05). Surface hardness of gypsum casts poured using impressions made from self-disinfecting alginate and conventional alginates were comparable. Self-disinfecting alginates may be employed in clinical practice as safe and effective materials to overcome the infection control issues without compromising on the properties of the material.

Silver nanoparticles coated with natural polysaccharides as models to study AgNP aggregation kinetics using UV-Visible spectrophotometry upon discharge in complex environments.

PubMed

Lodeiro, Pablo; Achterberg, Eric P; Pampín, Joaquín; Affatati, Alice; El-Shahawi, Mohammed S

2016-01-01

This study provides quantitative information on the aggregation and dissolution behaviour of silver nanoparticles (AgNPs) upon discharge in fresh and sea waters, represented here as NaCl solutions of increasing ionic strength (up to 1M) and natural fjord waters. Natural polysaccharides, sodium alginate (ALG) and gum Arabic (GA), were used as coatings to stabilize the AgNPs and the compounds acted as models to study AgNP aggregation kinetics. The DLVO theory was used to quantitatively describe the interactions between the AgNPs. The stability of AgNPs was established using UV-Visible spectrophotometry, including unique information collected during the first seconds of the aggregaton process. Alginate coating resulted in a moderate stabilization of AgNPs in terms of critical coagulation concentration (~82mM NaCl) and a low dissolution of <10% total Ag in NaCl solutions up to 1M. Gum Arabic coated AgNPs were more strongly stabilized, with ~7-30% size increase up to 77mM NaCl, but only when the silver ion content initially present in solution was low (<10% total Ag). The ALG and GA coated AgNPs showed a strongly enhanced stability in natural fjord waters (ca. 5h required to reduce the area of the surface plasmon resonance band (SPRB) by two fold) compared with NaCl at an equivalent ionic strength (1-2min period for a two fold SPRB reduction). This is ascribed to a stabilizing effect from dissolved organic matter present in natural fjord waters. Interestingly, for AgNP-GA solutions with 40% of total silver present as unreacted silver ions in the NP stock solution, fast aggregation kinetics were observed in NaCl solutions (SPRB area was reduced by ca. 50% within 40-150min), with even more rapid removal in fjord waters, attributed to the high amount of silver-chloride charged species, that interact with the NP coating and/or organic matter and reduce the NPs stabilization. Copyright © 2015 Elsevier B.V. All rights reserved.

Enzyme immobilization in novel alginate-chitosan core-shell microcapsules.

PubMed

Taqieddin, Ehab; Amiji, Mansoor

2004-05-01

Alginate-chitosan core-shell microcapsules were prepared in order to develop a biocompatible matrix for enzyme immobilization, where the protein is retained either in a liquid or solid core and the shell allows permeability control over substrates and products. The permeability coefficients of different molecular weight compounds (vitamin B2, vitamin B12, and myoglobin) were determined through sodium tripolyphosphate (Na-TPP)-crosslinked chitosan membrane. The microcapsule core was formed by crosslinking sodium alginate with either calcium or barium ions. The crosslinked alginate core was uniformly coated with a chitosan layer and crosslinked with Na-TPP. In the case of calcium alginate, the phosphate ions of Na-TPP were able to extract the calcium ions from alginate and liquefy the core. A model enzyme, beta-galactosidase, was immobilized in the alginate core and the catalytic activity was measured with o-nitrophenyl-beta-D-galactopyranoside (ONPG). Change in the activity of free and immobilized enzyme was determined at three different temperatures. Na-TPP crosslinked chitosan membranes were found to be permeable to solutes of up to 17,000Da molecular weight. The enzyme loading efficiency was higher in the barium alginate core (100%) as compared to the calcium alginate core (60%). The rate of ONPG conversion to o-nitrophenol was faster in the case of calcium alginate-chitosan microcapsules as compared to barium alginate-chitosan microcapsules. Barium alginate-chitosan microcapsules, however, did improve the stability of the enzyme at 37 degrees C relative to calcium alginate-chitosan microcapsules or free enzyme. This study illustrates a new method of enzyme immobilization for biotechnology applications using liquid or solid core and shell microcapsule technology.

Preparation and characterisation of alendronate-loaded chitosan microparticles obtained through the spray drying technique.

PubMed

Ochiuz, Lacramioara; Peris, José-Esteban

2009-03-01

Microparticles of chitosan (CHT) containing alendronate sodium (AL) were prepared in four drug:polymer ratios (1:1, 1:2, 1:4, 1:6) using the spray drying technique. The efficiency of the method was evaluated by determining production yield (about 70 %) and microencapsulation efficiency, which was almost 100 % in the case of all four of the formulations studied. Particles had a mean size of between 3.6 and 4.6 microm, and a near-spherical shape. The formulations with the highest content of AL (drug:polymer ratio 1:1 and 1:2) showed an asymmetrical distribution of particles, which were larger in size, and had a higher proportion of irregular particles than the other formulations. FT-IR analysis revealed an ionic interaction between AL and CHT. Differential scanning calorimetry and thermogravimetric analysis confirmed the microencapsulation of AL and the increased thermal stability of encapsulated AL. The dissolution profiles of AL from CHT microspheres, at pH values of 1.2 and 6.8, showed a delayed release of AL from microspheres, and the dissolution rate was dependent on the pH and the drug:polymer ratio. It can be concluded that spray drying is a suitable technique for preparing AL-loaded CHT microspheres, and that the drug:polymer ratio can be used to control the rate of AL release from microspheres.

Oxygen-dependent regulation of c-di-GMP synthesis by SadC controls alginate production in Pseudomonas aeruginosa.

PubMed

Schmidt, Annika; Hammerbacher, Anna Silke; Bastian, Mike; Nieken, Karen Jule; Klockgether, Jens; Merighi, Massimo; Lapouge, Karine; Poschgan, Claudia; Kölle, Julia; Acharya, K Ravi; Ulrich, Martina; Tümmler, Burkhard; Unden, Gottfried; Kaever, Volkhard; Lory, Stephen; Haas, Dieter; Schwarz, Sandra; Döring, Gerd

2016-10-01

Pseudomonas aeruginosa produces increased levels of alginate in response to oxygen-deprived conditions. The regulatory pathway(s) that links oxygen limitation to increased synthesis of alginate has remained elusive. In the present study, using immunofluorescence microscopy, we show that anaerobiosis-induced alginate production by planktonic PAO1 requires the diguanylate cyclase (DGC) SadC, previously identified as a regulator of surface-associated lifestyles. Furthermore, we found that the gene products of PA4330 and PA4331, located in a predicted operon with sadC, have a major impact on alginate production: deletion of PA4330 (odaA, for oxygen-dependent alginate synthesis activator) caused an alginate production defect under anaerobic conditions, whereas a PA4331 (odaI, for oxygen-dependent alginate synthesis inhibitor) deletion mutant produced alginate also in the presence of oxygen, which would normally inhibit alginate synthesis. Based on their sequence, OdaA and OdaI have predicted hydratase and dioxygenase reductase activities, respectively. Enzymatic assays using purified protein showed that unlike OdaA, which did not significantly affect DGC activity of SadC, OdaI inhibited c-di-GMP production by SadC. Our data indicate that SadC, OdaA and OdaI are components of a novel response pathway of P. aeruginosa that regulates alginate synthesis in an oxygen-dependent manner. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Alginate Lyase (AlgL) Activity Is Required for Alginate Biosynthesis in Pseudomonas aeruginosa

PubMed Central

Albrecht, Mark T.; Schiller, Neal L.

2005-01-01

To determine whether AlgL's lyase activity is required for alginate production in Pseudomonas aeruginosa, an algLΔ::Gmr mutant (FRD-MA7) was created. algL complementation of FRD-MA7 restored alginate production, but algL constructs containing mutations inactivating lyase activity did not, demonstrating that the enzymatic activity of AlgL is required for alginate production. PMID:15901714

Endocytosis of Red Blood Cell Microparticles by Pulmonary Endothelial Cells is Mediated By Rab5.

PubMed

Kim, Young; Abplanalp, William A; Jung, Andrew D; Schuster, Rebecca M; Lentsch, Alex B; Gulbins, Erich; Caldwell, Charles C; Pritts, Timothy A

2018-03-01

Microparticles are submicron vesicles shed from aging erythrocytes as a characteristic feature of the red blood cell (RBC) storage lesion. Exposure of pulmonary endothelial cells to RBC-derived microparticles promotes an inflammatory response, but the mechanisms underlying microparticle-induced endothelial cell activation are poorly understood. In the present study, cultured murine lung endothelial cells (MLECs) were treated with microparticles isolated from aged murine packed RBCs or vehicle. Microparticle-treated cells demonstrated increased expression of the adhesion molecules ICAM and E-selectin, as well as the cytokine, IL-6. To identify mechanisms that mediate these effects of microparticles on MLECs, cells were treated with microparticles covalently bound to carboxyfluorescein succinimidyl ester (CFSE) and cellular uptake of microparticles was quantified via flow cytometry. Compared with controls, there was a greater proportion of CFSE-positive MLECs from 15 min up to 24 h, suggesting endocytosis of the microparticles by endothelial cells. Colocalization of microparticles with lysosomes was observed via immunofluorescence, indicating endocytosis and endolysosomal trafficking. This process was inhibited by endocytosis inhibitors. SiRNA knockdown of Rab5 signaling protein in endothelial cells resulted in impaired microparticle uptake as compared with nonsense siRNA-treated cells, as well as an attenuation of the inflammatory response to microparticle treatment. Taken together, these data suggest that endocytosis of RBC-derived microparticles by lung endothelial cells results in endothelial cell activation. This response seems to be mediated, in part, by the Rab5 signaling protein.

Detection and quantification of microparticles from different cellular lineages using flow cytometry. Evaluation of the impact of secreted phospholipase A2 on microparticle assessment.

PubMed

Rousseau, Matthieu; Belleannee, Clemence; Duchez, Anne-Claire; Cloutier, Nathalie; Levesque, Tania; Jacques, Frederic; Perron, Jean; Nigrovic, Peter A; Dieude, Melanie; Hebert, Marie-Josee; Gelb, Michael H; Boilard, Eric

2015-01-01

Microparticles, also called microvesicles, are submicron extracellular vesicles produced by plasma membrane budding and shedding recognized as key actors in numerous physio(patho)logical processes. Since they can be released by virtually any cell lineages and are retrieved in biological fluids, microparticles appear as potent biomarkers. However, the small dimensions of microparticles and soluble factors present in body fluids can considerably impede their quantification. Here, flow cytometry with improved methodology for microparticle resolution was used to detect microparticles of human and mouse species generated from platelets, red blood cells, endothelial cells, apoptotic thymocytes and cells from the male reproductive tract. A family of soluble proteins, the secreted phospholipases A2 (sPLA2), comprises enzymes concomitantly expressed with microparticles in biological fluids and that catalyze the hydrolysis of membrane phospholipids. As sPLA2 can hydrolyze phosphatidylserine, a phospholipid frequently used to assess microparticles, and might even clear microparticles, we further considered the impact of relevant sPLA2 enzymes, sPLA2 group IIA, V and X, on microparticle quantification. We observed that if enriched in fluids, certain sPLA2 enzymes impair the quantification of microparticles depending on the species studied, the source of microparticles and the means of detection employed (surface phosphatidylserine or protein antigen detection). This study provides analytical considerations for appropriate interpretation of microparticle cytofluorometric measurements in biological samples containing sPLA2 enzymes.

Selective digestion of Ba2+/Ca2+ alginate gel microdroplets for single-cell handling

NASA Astrophysics Data System (ADS)

Odaka, Masao; Hattori, Akihiro; Matsuura, Kenji; Yasuda, Kenji

2018-06-01

Cells encapsuled by polymer microdroplets are an effective platform for the identification and separation of individual cells for single-cell-based analysis. However, a key challenge is to maintain and release the captured cells in the microdroplets selectively, nondestructively, and noninvasively. We developed a simple method of encapsulating cells in alginate microdroplets having different digestion characteristics. Cells were diluted with an alginate polymer of sol state and encapsulated into microdroplets with Ba2+ and Ca2+ by a spray method. When a chelating buffer was applied, alginate gel microdroplets were digested according to the difference in chelating efficiency of linkage-divalent cations; hence, two types of alginate microdroplets were formed. Moreover, we examined the capability of the alginate gel to exchange linkage-divalent cations and found that both Ca2+ exchange in Ba-alginate microdroplets and Ba2+ exchange in Ca-alginate microdroplets occurred. These results indicate that the potential applications of a mixture of alginate microdroplets with different divalent cations control the selective digestion of microdroplets to improve the high-throughput, high-content microdroplet-based separation, analysis, or storage of single cells.

Guluronic acid content as a factor affecting turbidity removal potential of alginate.

PubMed

Kıvılcımdan Moral, Çiğdem; Ertesvåg, Helga; Sanin, F Dilek

2016-11-01

Alginates are natural polymers composed of mannuronic and guluronic acid residues. They are currently extracted from brown algae; however, alginate can also be synthesized by some species of Azotobacter and Pseudomonas. Alginates with different proportion of mannuronic and guluronic acids are known to have different characteristics and form gels at different extents in the presence of calcium ions. The aim of this work was to investigate the usefulness of alginate as a non-toxic coagulant used in purification of drinking water. This study utilized alginates from Azotobacter vinelandii having different guluronic acid levels. These were obtained partly by changing the cultivation parameters, partly by epimerizing a purified alginate sample in vitro using the A. vinelandii mannuronan C-5 epimerase AlgE1. The different alginates were then used for coagulation together with calcium. The results showed that turbidity removal capability was dependent on the content of guluronic acid residues. For the best performing samples, the turbidity decreased from 10 NTU to 1 NTU by the use of only 2 mg/L of alginate and 1.5 mM of calcium chloride.

Investigation of cell viability and morphology in 3D bio-printed alginate constructs with tunable stiffness.

PubMed

Shi, Pujiang; Laude, Augustinus; Yeong, Wai Yee

2017-04-01

In this article, mouse fibroblast cells (L929) were seeded on 2%, 5%, and 10% alginate hydrogels, and they were also bio-printed with 2%, 5%, and 10% alginate solutions individually to form constructs. The elastic and viscous moduli of alginate solutions, their interior structure and stiffness, interactions of cells and alginate, cell viability, migration and morphology were investigated by rheometer, MTT assay, scanning electron microscope (SEM), and fluorescent microscopy. The three types of bio-printed scaffolds of distinctive stiffness were prepared, and the seeded cells showed robust viability either on the alginate hydrogel surfaces or in the 3D bio-printed constructs. Majority of the proliferated cells in the 3D bio-printed constructs weakly attached to the surrounding alginate matrix. The concentration of alginate solution and hydrogel stiffness influenced cell migration and morphology, moreover the cells formed spheroids in the bio-printed 10% alginate hydrogel construct. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1009-1018, 2017. © 2017 Wiley Periodicals, Inc.

Application of an amine functionalized biopolymer in the colonic delivery of glycyrrhizin: a design and in vivo efficacy study.

PubMed

Kumar De, Amit; Datta, Sriparna; Mukherjee, Arup

2013-01-01

In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery. Glycyrrhizic acid mono-ammonium salt was used as the model drug. Drug-loaded microparticles were formulated by ionic crosslinking using sodium tripolyphosphate. The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm. The FT-IR studies presented a possible interaction between the drug and the polymer. The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies. A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids. The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents. The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X1) and guar gum alkyl amine (X2) as the independant variables. The percent cumulative drug release at 240 mins (Q240), 720 mins (Q720), and at 1,440 mins (Q1440) were considered as the dependant variables. The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model. The tissue's nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group. The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals. The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.

PLGA-based drug delivery systems: importance of the type of drug and device geometry.

PubMed

Klose, D; Siepmann, F; Elkharraz, K; Siepmann, J

2008-04-16

Different types of ibuprofen- and lidocaine-loaded, poly(lactic-co-glycolic acid) (PLGA)-based microparticles and thin, free films of various dimensions were prepared and physico-chemically characterized in vitro. The obtained experimental results were analyzed using mathematical theories based on Fick's second law of diffusion. Importantly, the initial drug loadings were low in all cases (4%, w/w), simplifying the mathematical treatment and minimizing potential effects of the acidic/basic nature of the two model drugs on polymer degradation. Interestingly, the type of drug and device geometry strongly affected the resulting release kinetics and relative importance of the involved mass transport mechanisms. For instance, the relative release rate was almost unaffected by the system size in the case of spherical microparticles, but strongly depended on the thickness of thin, free films, irrespective of the type of drug. Ibuprofen and lidocaine release was found to be primarily diffusion controlled from the investigated PLGA-based microparticles for all system sizes, whereas diffusion was only dominant in the case of the thinnest free films. Interestingly, the type of drug did not significantly affect the resulting polymer degradation kinetics. However, ibuprofen release was always much faster than lidocaine release for all system geometries and sizes. This can probably be attributed to attractive ionic interactions between protonated, positively charged lidocaine ions and negatively charged, deprotonated carboxylic end groups of PLGA, hindering drug diffusion. The determined apparent diffusion coefficients of the drugs clearly point out that the mobility of an active agent in PLGA-based delivery systems does not only depend on its own physico-chemical properties and the type of PLGA used, but also to a large extent on the size and shape of the device. This has to be carefully taken into account when developing/optimizing this type of advanced drug delivery systems.

Fabrication of Covalently Crosslinked and Amine-Reactive Microcapsules by Reactive Layer-by-Layer Assembly of Azlactone-Containing Polymer Multilayers on Sacrificial Microparticle Templates

PubMed Central

Saurer, Eric M.; Flessner, Ryan M.; Buck, Maren E.; Lynn, David M.

2011-01-01

We report on the fabrication of covalently crosslinked and amine-reactive hollow microcapsules using ‘reactive’ layer-by-layer assembly to deposit thin polymer films on sacrificial microparticle templates. Our approach is based on the alternating deposition of layers of a synthetic polyamine and a polymer containing reactive azlactone functionality. Multilayered films composed of branched poly(ethylene imine) (BPEI) and poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) were fabricated layer-by-layer on the surfaces of calcium carbonate and glass microparticle templates. After fabrication, these films contained residual azlactone functionality that was accessible for reaction with amine-containing molecules. Dissolution of the calcium carbonate or glass cores using aqueous ethylenediamine tetraacetic acid (EDTA) or hydrofluoric acid (HF), respectively, led to the formation of hollow polymer microcapsules. These microcapsules were robust enough to encapsulate and retain a model macromolecule (FITC-dextran) and were stable for at least 22 hours in high ionic strength environments, in low and high pH solutions, and in several common organic solvents. Significant differences in the behaviors of capsules fabricated on CaCO3 and glass cores were observed and characterized using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Whereas capsules fabricated on CaCO3 templates collapsed upon drying, capsules fabricated on glass templates remained rigid and spherical. Characterization using EDS suggested that this latter behavior results, at least in part, from the presence of insoluble metal fluoride salts that are trapped or precipitate within the walls of capsules after etching of the glass cores using HF. Our results demonstrate that the assembly of BPEI/PVDMA films on sacrificial templates can be used to fabricate reactive microcapsules of potential use in a wide range of fields, including catalysis, drug and gene delivery, imaging, and biomedical research. PMID:21383867

Effect of dry heating and ionic gum on the physicochemical and release properties of starch from Dioscorea.

PubMed

Vashisht, Deepika; Pandey, Anima; Hermenean, Anca; Yáñez-Gascón, Maria Josefa; Pérez-Sánchez, Horacio; Kumar, K Jayaram

2017-02-01

To meet the ever increasing industrial demand for excipients with desirable properties, modified starch is regarded as an alternative to it. With this in mind, the present study focuses on the modification of starches of Dioscorea from Jharkhand (India) using dry heat treatment with and without ionic gum. Modified starches were prepared using sodium alginate (1% w/w). Native and modified starches were subjected to heat treatment at 130°C for 2h and 4h. The effect of heating and ionic gum on the properties of Dioscorea starch was investigated. The amylose content, water holding capacity, micromeritic properties, swelling power, solubility and morphology of starches were evaluated. Dry heat treatment of starches without gum showed an increment in water-holding capacity after two-hours heating, but no such increment was found after four-hours heating. Oil binding capacity of starches modified with gum varied from 62% to 78%. Strongest effect of heat treatment occurred on the morphology of starches and thereby modified starches showed distorted surface morphology. Amylose content (21.09-21.89%) found to be decreased with the addition of gum which lead to decrease in paste clarity. Starches heated with gum at high-temperature resulted in restrict swelling and slight increase in solubility. Micromeritic properties of the modified starches showed the good flow properties. Further, the modified starches were investigated for in-vitro release studies and that the thermally modified derivatives can be a good prospect in slow release formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Microparticles Mediate Hepatic Ischemia-Reperfusion Injury and Are the Targets of Diannexin (ASP8597)

PubMed Central

Wong, Heng Jian; Croft, Kevin; Mori, Trevor; Farrell, Geoffrey C.

2014-01-01

Background & Aims Ischemia–reperfusion injury (IRI) can cause hepatic failure after liver surgery or transplantation. IRI causes oxidative stress, which injures sinusoidal endothelial cells (SECs), leading to recruitment and activation of Kupffer cells, platelets and microcirculatory impairment. We investigated whether injured SECs and other cell types release microparticles during post-ischemic reperfusion, and whether such microparticles have pro-inflammatory, platelet-activating and pro-injurious effects that could contribute to IRI pathogenesis. Methods C57BL6 mice underwent 60 min of partial hepatic ischemia followed by 15 min–24 hrs of reperfusion. We collected blood and liver samples, isolated circulating microparticles, and determined protein and lipid content. To establish mechanism for microparticle production, we subjected murine primary hepatocytes to hypoxia-reoxygenation. Because microparticles express everted phosphatidylserine residues that are the target of annexin V, we analyzed the effects of an annexin V-homodimer (Diannexin or ASP8597) on post-ischemia microparticle production and function. Results Microparticles were detected in the circulation 15–30 min after post-ischemic reperfusion, and contained markers of SECs, platelets, natural killer T cells, and CD8+ cells; 4 hrs later, they contained markers of macrophages. Microparticles contained F2-isoprostanes, indicating oxidative damage to membrane lipids. Injection of mice with TNF-α increased microparticle formation, whereas Diannexin substantially reduced microparticle release and prevented IRI. Hypoxia-re-oxygenation generated microparticles from primary hepatocytes by processes that involved oxidative stress. Exposing cultured hepatocytes to preparations of microparticles isolated from the circulation during IRI caused injury involving mitochondrial membrane permeability transition. Microparticles also activated platelets and induced neutrophil migration in vitro. The inflammatory properties of microparticles involved activation of NF-κB and JNK, increased expression of E-selectin, P-selectin, ICAM-1 and VCAM-1. All these processes were blocked by coating microparticles with Diannexin. Conclusions Following hepatic IRI, microparticles circulate and can be taken up by hepatocytes, where they activate signaling pathways that mediate inflammation and hepatocyte injury. Diannexin prevents microparticle formation and subsequent inflammation. PMID:25222287

Syllabus of Dental Materials

DTIC Science & Technology

1984-07-01

Rubberloid Van R Dental Prod. Surgident Lactona Corp. Alginates Coe Alginate Coe Labs o Jeltrate L.D. Caulk Kerr Alginate Kerr/Sybron Alginate S.S. White Co...Surgident- Alginate Lactona Corp. Unijel II Unitek Corp. O Combination Agar/a ig inate Colloid 80 U.S. Shiza Corp. Dentloid Denterials, Ltd...66061 (215) 277-3800 (913) 782-2200 Shofu Dental Corp. Lactona Corp. (subsidary of 4025 Bohannon Dr. Warner-Lambert Co.) Menlo Park, CA 94025 . Academy

Novel injectable, self-gelling hydrogel-microparticle composites for bone regeneration consisting of gellan gum and calcium and magnesium carbonate microparticles.

PubMed

Douglas, Timothy E L; Łapa, Agata; Reczyńska, Katarzyna; Krok-Borkowicz, Małgorzata; Pietryga, Krzysztof; Samal, Sangram Keshari; Declercq, Heidi A; Schaubroeck, David; Boone, Marijn; Van der Voort, Pascal; De Schamphelaere, Karel; Stevens, Christian V; Bliznuk, Vitaliy; Balcaen, Lieve; Parakhonskiy, Bogdan V; Vanhaecke, Frank; Cnudde, Veerle; Pamuła, Elżbieta; Skirtach, Andre G

2016-11-21

The suitability of hydrogel biomaterials for bone regeneration can be improved by incorporation of an inorganic phase in particle form, thus maintaining hydrogel injectability. In this study, carbonate microparticles containing different amounts of calcium (Ca) and magnesium (Mg) were added to solutions of the anionic polysaccharide gellan gum (GG) to crosslink GG by release of Ca 2+ and Mg 2+ from microparticles and thereby induce formation of hydrogel-microparticle composites. It was hypothesized that increasing Mg content of microparticles would promote GG hydrogel formation. The effect of Mg incorporation on cytocompatibility and cell growth was also studied. Microparticles were formed by mixing Ca 2+ and Mg 2+ and [Formula: see text] ions in varying concentrations. Microparticles were characterized physiochemically and subsequently mixed with GG solution to form hydrogel-microparticle composites. The elemental Ca:Mg ratio in the mineral formed was similar to the Ca:Mg ratio of the ions added. In the absence of Mg, vaterite was formed. At low Mg content, magnesian calcite was formed. Increasing the Mg content further caused formation of amorphous mineral. Microparticles of vaterite and magnesium calcite did not induce GG hydrogel formation, but addition of Mg-richer amorphous microparticles induced gelation within 20 min. Microparticles were dispersed homogeneously in hydrogels. MG-63 osteoblast-like cells were cultured in eluate from hydrogel-microparticle composites and on the composites themselves. All composites were cytocompatible. Cell growth was highest on composites containing particles with an equimolar Ca:Mg ratio. In summary, carbonate microparticles containing a sufficient amount of Mg induced GG hydrogel formation, resulting in injectable, cytocompatible hydrogel-microparticle composites.

Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels

PubMed Central

Ma, Kun; Titan, Ashley L.; Stafford, Melissa; Zheng, Chun hua; Levenston, Marc E.

2012-01-01

Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with distinct advantages and disadvantages to each material. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40 mg/mL fibrinogen blended with 8 mg/mL alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition. PMID:22750738

Physical, mechanical, and barrier properties of sodium alginate/gelatin emulsion based-films incorporated with canola oil

NASA Astrophysics Data System (ADS)

Syarifuddin, A.; Hasmiyani; Dirpan, A.; Mahendradatta, M.

2017-12-01

The development of mixed emulsion-based films formed by sodium alginate/gelatin incorporated with canola oil can offer particular properties such as water vapor barrier properties. The different ratios of sodium alginate/gelatin and sodium alginate/gelatin emulsion-based films incorporated with canola oil were developed and their effects on films’ physical, mechanical and barrier properties were assessed. Here we set out to examine whether canola oil addition and different ratio of sodium alginate/gelatin modified physical, mechanical, and barrier properties of films. To do so, the films were prepared by vary the ratio of sodium alginate/gelatin (2.5, 1, 0.5). Canola oil addition induced changes in moisture content, thickness, solubility, water vapor transmission rate (WVTR), percent elongation at break (p<0.05). In addition, it is apparent that varying ratio of sodium alginate to gelatin induced change the mechanical properties of films. The reduction of sodium alginate to gelatin decreased the tensile strength of both films. Improved values of WVTR, tensile strength and solubility at break were observed when the ratio of sodium alginate/gelatin emulsion film incorporated with canola oil was 2.5. Therefore, different ratio of sodium alginate/gelatin incorporated with canola oil can be used to tailor emulsion films with enhanced water vapor barrier and mechanical properties.

Dopamine-assisted fixation of drug-loaded polymeric multilayers to osteoarticular implants for tuberculosis therapy.

PubMed

Li, Dan; Li, Litao; Ma, Yunlong; Zhuang, Yaping; Li, Dawei; Shen, Hong; Wang, Xing; Yang, Fei; Ma, Yuanzheng; Wu, Decheng

2017-03-28

Currently, the major issues in the treatment of osteoarticular tuberculosis (TB) after implant placement are low drug concentration at the infected focus and drug resistance resulting from the long-term chemotherapy. The application of drug-loaded polymeric multilayers on implantable devices offers a promising solution to the problems. Herein, a poly(ethylene glycol)-based hydrogel film embedded with isoniazid (INH)-loaded alginate microparticles was fixed to Ti implants via adhesive polydopamine, subsequently capped by poly(lactic-co-glycolic acid) membranes for the sustained and localized delivery of the anti-TB drug. The antibacterial efficacy of the released INH was confirmed by a 4.5 ± 0.8 cm inhibition zone formed in the fourth week after inoculation of Mycobacterium tuberculosis. The INH-loaded Ti implants showed no toxicity to the osteoblast cell and provided a consistent drug release for nearly one week in vitro. The release profile in vivo showed a high local concentration and low systemic exposure. The local INH concentration could be kept higher than its minimum inhibitory concentration over a period of 8 weeks, which proves that it is a promising strategy to improve the severe osteoarticular TB treatment.

Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.

PubMed

Zinger, Anna; Latham, Sharissa L; Combes, Valery; Byrne, Scott; Barnett, Michael H; Hawke, Simon; Grau, Georges E

2016-12-01

No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS. © The Author(s), 2016.

Circulating microparticles from obstructive sleep apnea syndrome patients induce endothelin-mediated angiogenesis.

PubMed

Tual-Chalot, Simon; Gagnadoux, Frédéric; Trzepizur, Wojciech; Priou, Pascaline; Andriantsitohaina, Ramaroson; Martinez, M Carmen

2014-02-01

Microparticles are deemed true biomarkers and vectors of biological information between cells. Depending on their origin, the composition of microparticles varies and the subsequent message transported by them, such as proteins, mRNA, or miRNA, can differ. In obstructive sleep apnea syndrome (OSAS), circulating microparticles are associated with endothelial dysfunction by reducing endothelial-derived nitric oxide production. Here, we have analyzed the potential role of circulating microparticles from OSAS patients on the regulation of angiogenesis and the involved pathway. VEGF content carried by circulating microparticles from OSAS patients was increased when compared with microparticles from non-OSAS patients. Circulating microparticles from OSAS patients induced an increase of angiogenesis that was abolished in the presence of the antagonist of endothelin-1 receptor type B. In addition, endothelin-1 secretion was increased in human endothelial cells treated by OSAS microparticles. We highlight that circulating microparticles from OSAS patients can modify the secretome of endothelial cells leading to angiogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation, characterisation and viability of encapsulated Trichoderma harzianum UPM40 in alginate-montmorillonite clay.

PubMed

Adzmi, Fariz; Meon, Sariah; Musa, Mohamed Hanafi; Yusuf, Nor Azah

2012-01-01

Microencapsulation is a process by which tiny parcels of an active ingredient are packaged within a second material for the purpose of shielding the active ingredient from the surrounding environment. This study aims to determine the ability of the microencapsulation technique to improve the viability of Trichoderma harzianum UPM40 originally isolated from healthy groundnut roots as effective biological control agents (BCAs). Alginate was used as the carrier for controlled release, and montmorillonite clay (MMT) served as the filler. The encapsulated Ca-alginate-MMT beads were characterised using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The FTIR results showed the interaction between the functional groups of alginate and MMT in the Ca-alginate-MMT beads. Peaks at 1595, 1420 and 1020 cm(-1) characterised alginate, and peaks at 1028 and 453 cm(-1) characterised MMT; both sets of peaks appeared in the Ca-alginate-MMT FTIR spectrum. The TGA analysis showed an improvement in the thermal stability of the Ca-alginate-MMT beads compared with the alginate beads alone. SEM analysis revealed a homogeneous distribution of the MMT particles throughout the alginate matrix. T. harzianum UPM40 was successfully encapsulated in the Ca-alginate-MMT beads. Storage analysis of the encapsulated T. harzianum UPM40 showed that the low storage temperature of 5°C resulted in significantly (p < 0.05) better storage compared with room temperature (30°C).

Synthesis of porous inorganic hollow fibers without harmful solvents.

PubMed

Shukla, Sushumna; de Wit, Patrick; Luiten-Olieman, Mieke W J; Kappert, Emiel J; Nijmeijer, Arian; Benes, Nieck E

2015-01-01

A route for the fabrication of porous inorganic hollow fibers with high surface-area-to-volume ratio that avoids harmful solvents is presented. The approach is based on bio-ionic gelation of an aqueous mixture of inorganic particles and sodium alginate during wet spinning. In a subsequent thermal treatment, the bio-organic material is removed and the inorganic particles are sintered. The method is applicable to the fabrication of various inorganic fibers, including metals and ceramics. The route completely avoids the use of organic solvents, such as N-methyl-2-pyrrolidone, and additives associated with the currently used fiber fabrication methods. In addition, it inherently avoids the manifestation of so-called macro voids and allows the facile incorporation of additional metal oxides in the inorganic hollow fibers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Construction of Injectable Double-Network Hydrogels for Cell Delivery.

PubMed

Yan, Yan; Li, Mengnan; Yang, Di; Wang, Qian; Liang, Fuxin; Qu, Xiaozhong; Qiu, Dong; Yang, Zhenzhong

2017-07-10

Herein we present a unique method of using dynamic cross-links, which are dynamic covalent bonding and ionic interaction, for the construction of injectable double-network (DN) hydrogels, with the objective of cell delivery for cartilage repair. Glycol chitosan and dibenzaldhyde capped poly(ethylene oxide) formed the first network, while calcium alginate formed the second one, and in the resultant DN hydrogel, either of the networks could be selectively removed. The moduli of the DN hydrogel were significantly improved compared to that of the parent single-network hydrogels and were tunable by changing the chemical components. In situ 3D cell encapsulation could be easily performed by mixing cell suspension to the polymer solutions and transferred through a syringe needle before sol-gel transition. Cell proliferation and mediated differentiation of mouse chondrogenic cells were achieved in the DN hydrogel extracellular matrix.

Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.

PubMed

Zubairova, Laily D; Nabiullina, Roza M; Nagaswami, Chandrasekaran; Zuev, Yuriy F; Mustafin, Ilshat G; Litvinov, Rustem I; Weisel, John W

2015-12-04

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.

Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots

PubMed Central

Zubairova, Laily D.; Nabiullina, Roza M.; Nagaswami, Chandrasekaran; Zuev, Yuriy F.; Mustafin, Ilshat G.; Litvinov, Rustem I.; Weisel, John W.

2015-01-01

Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1–0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis. PMID:26635081

Preparation of aminated chitosan/alginate scaffold containing halloysite nanotubes with improved cell attachment.

PubMed

Amir Afshar, Hamideh; Ghaee, Azadeh

2016-10-20

The chemical nature of biomaterials play important role in cell attachment, proliferation and migration in tissue engineering. Chitosan and alginate are biodegradable and biocompatible polymers used as scaffolds for various medical and clinical applications. Amine groups of chitosan scaffolds play an important role in cell attachment and water adsorption but also associate with alginate carboxyl groups via electrostatic interactions and hydrogen bonding, consequently the activity of amine groups in the scaffold decreases. In this study, chitosan/alginate/halloysite nanotube (HNTs) composite scaffolds were prepared using a freeze-drying method. Amine treatment on the scaffold occurred through chemical methods, which in turn caused the hydroxyl groups to be replaced with carboxyl groups in chitosan and alginate, after which a reaction between ethylenediamine, 1-ethyl-3,(3-dimethylaminopropyl) carbodiimide (EDC) and scaffold triggered the amine groups to connect to the carboxyl groups of chitosan and alginate. The chemical structure, morphology and mechanical properties of the composite scaffolds were investigated by FTIR, CHNS, SEM/EDS and compression tests. The electrostatic attraction and hydrogen bonding between chitosan, alginate and halloysite was confirmed by FTIR spectroscopy. Chitosan/alginate/halloysite scaffolds exhibit significant enhancement in compressive strength compared with chitosan/alginate scaffolds. CHNS and EDS perfectly illustrate that amine groups were effectively introduced in the aminated scaffold. The growth and cell attachment of L929 cells as well as the cytotoxicity of the scaffolds were investigated by SEM and Alamar Blue (AB). The results indicated that the aminated chitosan/alginate/halloysite scaffold has better cell growth and cell adherence in comparison to that of chitosan/alginate/halloysite samples. Aminated chitosan/alginate/halloysite composite scaffolds exhibit great potential for applications in tissue engineering, ideally in cell culture. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterisation of bare and tannase-loaded calcium alginate beads by microscopic, thermogravimetric, FTIR and XRD analyses.

PubMed

Larosa, Claudio; Salerno, Marco; de Lima, Juliana Silva; Merijs Meri, Remo; da Silva, Milena Fernandes; de Carvalho, Luiz Bezerra; Converti, Attilio

2018-08-01

Incorporating enzymes into calcium alginate beads is an effective method to immobilise them and to preserve, at the same time, their catalytic activity. Sodium alginate was mixed with Aspergillus ficuum tannase in aqueous solution, and tannase-loaded calcium alginate beads were prepared using a simple droplet-based microfluidic system. Extensive experimental analysis was carried out to characterise the samples. Microscopic imaging revealed morphological differences between the surfaces of bare alginate matrix and tannase-loaded alginate beads. Thermal analysis allowed assessing the hydration contents of alginate and revealed the presence of tannase entrapped in the loaded beads, which was confirmed by vibrational spectroscopy. X-ray diffraction allowed us to conclude that alginate of tannase-loaded beads is not crystalline, which would make them suitable as carriers for possible controlled release. Moreover, they could be used in food applications to improve tea quality or clarify juices. Copyright © 2018 Elsevier B.V. All rights reserved.

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

PubMed Central

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2014-01-01

This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 μm containing ~100 ng of BMP-7. The release study profile indicates that nearly 98% of the BMP-7 coated on the microparticles was released in a period of 18 days while only 36% of the BMP-7 encapsulated in the microparticles was released in the same time period. Cell attachment study indicated that the BMP-7 coated microparticles have many cells adhered on the microparticles in comparison with microparticles without growth factors on day 10. DNA assay indicated a statistical significant increase (p<0.05) in the amount of DNA obtained from BMP-7 encapsulated and coated microparticles in comparison with microparticles without any growth factors. A real time RT-PCR experiment was performed to determine the expression of a few osteoblast specific genes - Dlx5, runx2, osterix, osteopontin, osteocalcin, and bone sialoprotein. The results thus suggest that chitosan microparticles obtained by coacervation method are biocompatible and helps in improving the encapsulation efficiency of BMP-7. Also BMP-7 incorporated in the microparticles is being released in a controlled fashion to support attachment, proliferation and differentiation of pre-osteoblasts, thus acting as a good scaffold for bone tissue regeneration. PMID:24497318

Optimization of alginate purification using polyvinylidene difluoride membrane filtration: Effects on immunogenicity and biocompatibility of three-dimensional alginate scaffolds

PubMed Central

Sondermeijer, Hugo P; Witkowski, Piotr; Woodland, David; Seki, Tetsunori; Aangenendt, Frank J; van der Laarse, Arnoud; Itescu, Silviu; Hardy, Mark A

2017-01-01

Sodium alginate is an effective biomaterial for tissue engineering applications. Non-purified alginate is contaminated with protein, lipopolysaccharide, DNA, and RNA, which could elicit adverse immunological reactions. We developed a purification protocol to generate biocompatible alginate based on (a) activated charcoal treatment, (b) use of hydrophobic membrane filtration (we used hydrophobic polyvinylidene difluoride membranes to remove organic contaminants), (c) dialysis, and finally (d) ethanol precipitation. Using this approach, we could omit pre-treatment with chloroform and significantly reduce the quantities of reagents used. Purification resulted in reduction of residual protein by 70% down to 0.315 mg/g, DNA by 62% down to 1.28 μg/g, and RNA by 61% down to less than 10 μg/g, respectively. Lipopolysaccharide levels were reduced by >90% to less than 125 EU/g. Purified alginate did not induce splenocyte proliferation in vitro. Three-dimensional scaffolds generated from purified alginate did not elicit a significant foreign body reaction, fibrotic overgrowth, or macrophage infiltration 4 weeks after implantation. This study describes a simplified and economical alginate purification method that results in alginate purity, which meets clinically useful criteria. PMID:27114440

Screening of alginate lyase-excreting microorganisms from the surface of brown algae.

PubMed

Wang, Mingpeng; Chen, Lei; Zhang, Zhaojie; Wang, Xuejiang; Qin, Song; Yan, Peisheng

2017-12-01

Alginate lyase is a biocatalyst that degrades alginate to produce oligosaccharides, which have many bioactive functions and could be used as renewable biofuels. Here we report a simple and sensitive plate assay for screening alginate lyase-excreting microorganisms from brown algae. Brown algae Laminaria japonica, Sargassum horneri and Sargassum siliquatrum were cultured in sterile water. Bacteria growing on the surface of seaweeds were identified and their capacity of excreting alginate lyase was analyzed. A total of 196 strains were recovered from the three different algae samples and 12 different bacterial strains were identified capable of excreting alginate lyases. Sequence analysis of the 16S rRNA gene revealed that these alginate lyase-excreting strains belong to eight genera: Paenibacillus (4/12), Bacillus (2/12), Leclercia (1/12), Isoptericola (1/12), Planomicrobium (1/12), Pseudomonas (1/12), Lysinibacillus (1/12) and Sphingomonas (1/12). Further analysis showed that the LJ-3 strain (Bacillus halosaccharovorans) had the highest enzyme activity. To our best knowledge, this is the first report regarding alginate lyase-excreting strains in Paenibacillus, Planomicrobium and Leclercia. We believe that our method used in this study is relatively easy and reliable for large-scale screening of alginate lyase-excreting microorganisms.

Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.

PubMed

Stops, Frances; Fell, John T; Collett, John H; Martini, Luigi G

2008-02-28

Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.

21 CFR 582.7610 - Potassium alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

21 CFR 582.7610 - Potassium alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

21 CFR 582.7610 - Potassium alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium alginate. 582.7610 Section 582.7610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Potassium alginate. (a) Product. Potassium alginate. (b) Conditions of use. This substance is generally...

21 CFR 582.7187 - Calcium alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Calcium alginate. 582.7187 Section 582.7187 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium alginate. (a) Product. Calcium alginate. (b) Conditions of use. This substance is generally...

21 CFR 582.7187 - Calcium alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Calcium alginate. 582.7187 Section 582.7187 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium alginate. (a) Product. Calcium alginate. (b) Conditions of use. This substance is generally...

21 CFR 582.7187 - Calcium alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Calcium alginate. 582.7187 Section 582.7187 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium alginate. (a) Product. Calcium alginate. (b) Conditions of use. This substance is generally...

In vivo degradation of alginate in the presence and in the absence of resistant starch.

PubMed

Jonathan, Melliana; Souza da Silva, Carol; Bosch, Guido; Schols, Henk; Gruppen, Harry

2015-04-01

This study evaluated the intestinal degradability of alginate during 74 days intake in pigs as models for humans. Diets contained pregelatinized starch, retrograded starch, alginate, or a mix of retrograded starch and alginate. Faeces were collected on day 1, 3, 7, 14, 39 and 74. Clear trends in intestinal alginate degradation were observed. Up to day 39, the total tract digestibility of alginate was limited (0.52 ± 0.10), and was lower with the inclusion of retrograded starch in the diet (0.34 ± 0.02). More than 90% of the faecal alginate was insoluble in water, which may explain the low digestibility of the alginate. The digestibility of mannuronic acid (M) was 2-3 times higher than that of guluronic acid (G). The changes of G:M ratio and the relative amounts of alginate oligosaccharides between day 39 and 74 indicated that the microbiota needed more than 39 days to adapt to alginate. This study demonstrated that in-depth analyses of dietary fibres are valuable in understanding the fate of the dietary fibres in the large intestine as it was shown that degradation of a dietary fibre depends not only on the properties of the fibre itself, but also on the other dietary fibres present in the diet and the adaptation time. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vivo evaluation of EPO-secreting cells immobilized in different alginate-PLL microcapsules.

PubMed

Ponce, S; Orive, G; Hernández, R M; Gascón, A R; Canals, J M; Muñoz, M T; Pedraz, J L

2006-11-01

Alginates are the most employed biomaterials for cell encapsulation due to their abundance, easy gelling properties and apparent biocompatibility. However, as natural polymers different impurities including endotoxins, proteins and polyphenols can be found in their composition. Several purification protocols as well as different batteries of assays to prove the biocompatibility of the alginates in vitro have been recently developed. However, little is known about how the use of alginates with different purity grade may affect the host immune response after their implantation in vivo. The present paper investigates the long-term functionality and biocompatibility of murine erythropoietin (EPO) secreting C2C12 cells entrapped in microcapsules elaborated with alginates with different properties (purity, composition and viscosity). Results showed that independently of the alginate type employed, the animals presented elevated hematocrit levels until day 130, remaining at values between 70-87%. However, histological analysis of the explanted devices showed higher overgrowth around non-biomedical grade alginate microcapsules which could be directly related with higher impurity content of this type of alginate. Although EPO delivery may be limited by the formation of a fibrotic layer around non-biomedical grade alginate microcapsules, the high EPO secretion of the encapsulated cells together with the pharmacodynamic behaviour and the angiogenic and immune-modulatory properties of EPO result in no direct correlation between the biocompatibility of the alginate and the therapeutic response obtained.

Preparation and release characteristics of polymer-coated and blended alginate microspheres.

PubMed

Lee, D W; Hwang, S J; Park, J B; Park, H J

2003-01-01

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.

Clinical and laboratory studies of the antacid and raft-forming properties of Rennie alginate suspension.

PubMed

Tytgat, G N; Simoneau, G

2006-03-15

Acid pockets at the gastro-oesophageal junction escape buffering from meals in the stomach. Combining high-dose antacid with alginate may therefore be of benefit in gastro-oesophageal reflux disease. To characterize the antacid and raft-forming properties of Rennie alginate suspension (containing high-dose antacid and alginate; Bayer Consumer Care, Bladel, the Netherlands). The in vitro acid-neutralizing capacity of Rennie algniate was compared with Gaviscon (Reckitt Benckiser, Slough, UK) by pH-recorded HCl titration. Alginate raft weight formed in vitro at different pH was used to evaluate the pH dependency of raft formation with each product. A double-blind, placebo-controlled, randomized crossover study also compared the antacid activity of Rennie alginate vs. placebo in vivo using continuous intragastric pH monitoring in 12 healthy fasting volunteers. Compared with Gaviscon, Rennie alginate had a higher acid-neutralizing capacity, greater maximum pH and longer duration of antacid activity in vitro. However, the two products produced comparable alginate rafts at each pH evaluated. In vivo, Rennie alginate provided rapid, effective and long-lasting acid neutralization, with an onset of action of <5 min, and duration of action of almost 90 min. The dual mode of action of Rennie alginate offers an effective treatment option for mild symptomatic gastro-oesophageal reflux disease particularly considering recent findings regarding 'acid pockets'.

Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

PubMed Central

Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

2013-01-01

Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

Nanocarriers Made from Non-Ionic Surfactants or Natural Polymers for Pulmonary Drug Delivery.

PubMed

Carter, K C; Puig-Sellart, M

2016-01-01

Treatment by the pulmonary route can be used for drugs that act locally in the lungs (e.g. lung cancer) or non-invasive administration of drugs that act systemically (e.g. diabetes). The potential of using drug delivery systems (DDS) formed from non-ionic surfactants or natural products for pulmonary drug delivery are reviewed. The effectiveness of each DDS depends on it ability to not only entrap the relevant drug and alter its bio distribution, but also its ability to withstand the physical stresses during nebulization and for the nebuliser to produce aerosol particles with the size for deposition in the appropriate part of the lungs. Different methods must be used to prepare nanoparticles (NP) using non-ionic surfactants, or biocompatible polymers from natural proteins or sugars, and the aqueous solubility of the drug also influences the manufacture method. NP produced using non-ionic surfactants, proteins such as collagen, albumin or gluten, and polysaccharides such as chitosan, hyaluronate, cellulose, carrageenans, alginate or starch has successfully delivered different types of drugs given by the pulmonary route. Drug entrapment efficiency depends on the DDS constituents and the manufacture method used. Large scale manufacture of DDS from natural products is technically challenging but changing from batch manufacture to continuous manufacturing processes has addressed some of these issues, and inclusion of a spray drying step has been beneficial in some cases. DDS for lung delivery can be produced using natural products but identifying a cost effective manufacture method may be challenging and the impact of using different type of nebulisers on the physiochemical characteristics of the aerosolised formulation should be an essential part of formulation development. This would ensure that some of the development work e.g. stability studies do not have to be repeated as they will identify if a carrier to protect the DDS from the physical trauma caused by nebulisation.

Platelet and not erythrocyte microparticles are procoagulant in transfused thalassaemia major patients.

PubMed

Agouti, Imane; Cointe, Sylvie; Robert, Stéphane; Judicone, Coralie; Loundou, Anderson; Driss, Fathi; Brisson, Alain; Steschenko, Dominique; Rose, Christian; Pondarré, Corinne; Bernit, Emmanuelle; Badens, Catherine; Dignat-George, Françoise; Lacroix, Romaric; Thuret, Isabelle

2015-11-01

The level of circulating platelet-, erythrocyte-, leucocyte- and endothelial-derived microparticles detected by high-sensitivity flow cytometry was investigated in 37 β-thalassaemia major patients receiving a regular transfusion regimen. The phospholipid procoagulant potential of the circulating microparticles and the microparticle-dependent tissue factor activity were evaluated. A high level of circulating erythrocyte- and platelet-microparticles was found. In contrast, the number of endothelial microparticles was within the normal range. Platelet microparticles were significantly higher in splenectomized than in non-splenectomized patients, independent of platelet count (P < 0·001). Multivariate analysis indicated that phospholipid-dependent procoagulant activity was influenced by both splenectomy (P = 0·001) and platelet microparticle level (P < 0·001). Erythrocyte microparticles were not related to splenectomy, appear to be devoid of proper procoagulant activity and no relationship between their production and haemolysis, dyserythropoiesis or oxidative stress markers could be established. Intra-microparticle labelling with anti-HbF antibodies showed that they originate only partially (median of 28%) from thalassaemic erythropoiesis. In conclusion, when β-thalassaemia major patients are intensively transfused, the procoagulant activity associated with thalassaemic erythrocyte microparticles is probably diluted by transfusions. In contrast, platelet microparticles, being both more elevated and more procoagulant, especially after splenectomy, may contribute to the residual thrombotic risk reported in splenectomized multi-transfused β-thalassaemia major patients. © 2015 John Wiley & Sons Ltd.

High-Mobility Group Box 1 From Hypoxic Trophoblasts Promotes Endothelial Microparticle Production and Thrombophilia in Preeclampsia.

PubMed

Hu, Yae; Yan, Ruhong; Zhang, Ce; Zhou, Zhichao; Liu, Meng; Wang, Can; Zhang, Hong; Dong, Liang; Zhou, Tiantian; Wu, Yi; Dong, Ningzheng; Wu, Qingyu

2018-04-12

Thrombophilia is a major complication in preeclampsia, a disease associated with placental hypoxia and trophoblast inflammation. Preeclampsia women are known to have increased circulating microparticles that are procoagulant, but the underlying mechanisms remain unclear. In this study, we sought to understand the mechanism connecting placental hypoxia, circulating microparticles, and thrombophilia. We analyzed protein markers on plasma microparticles from preeclampsia women and found that the increased circulating microparticles were mostly from endothelial cells. In proteomic studies, we identified HMGB1 (high-mobility group box 1), a proinflammatory protein, as a key factor from hypoxic trophoblasts in stimulating microparticle production in human umbilical vein endothelial cells. Immunodepletion or inhibition of HMGB1 in the conditioned medium from hypoxic human trophoblasts abolished the endothelial microparticle-stimulating activity. Conversely, recombinant HMGB1 stimulated microparticle production in cultured human umbilical vein endothelial cells. The microparticles from recombinant HMGB1-stimulated human umbilical vein endothelial cells promoted blood coagulation and neutrophil activation in vitro. Injection of recombinant HMGB1 in pregnant mice increased plasma endothelial microparticles and promoted blood coagulation. In preeclampsia women, elevated placental HMGB1 expression was detected and high levels of plasma HMGB1 correlated with increased plasma endothelial microparticles. Our results indicate that placental hypoxia-induced HMGB1 expression and release from trophoblasts are important mechanism underlying increased circulating endothelial microparticles and thrombophilia in preeclampsia. © 2018 American Heart Association, Inc.

Controlling the size of alginate gel beads by use of a high electrostatic potential.

PubMed

Klokk, T I; Melvik, J E

2002-01-01

The effect of several parameters on the size of alginate beads produced by use of an electrostatic potential bead generator was examined. Parameters studied included needle diameter, electrostatic potential, alginate solution flow rate, gelling ion concentration and alginate concentration and viscosity, as well as alginate composition. Bead size was found to decrease with increasing electrostatic potential, but only down to a certain level. Minimum bead size was reached at between 2-4 kV/cm for the needles tested. The smallest alginate beads produced (using a needle with inner diameter 0.18 mm) had a mean diameter of approximately 300 microm. Bead size was also found to be dependent upon the flow rate of the fed alginate solution. Increasing the gelling ion concentration resulted in a moderate decrease in bead size. The concentration and viscosity of the alginate solution also had an effect on bead size as demonstrated by an increased bead diameter when the concentration or viscosity was increased. This effect was primarily an effect of the viscosity properties of the solution, which led to changes in the rate of droplet formation in the bead generator. Lowering the flow rate of the alginate solution could partly compensate for the increase in bead size with increased viscosity. For a constant droplet size, alginates with a low G block content (F(GG) approximately 0.20) resulted in approximately 30% smaller beads than alginates with a high G block content (F(GG) approximately 0.60). This is explained as a result of differences in the shrinking properties of the beads.

Spray-dried chitosan/acid/NaCl microparticles enhance saltiness perception.

PubMed

Yi, Cheng; Tsai, Min-Lang; Liu, Tristan

2017-09-15

The composition, physicochemical properties and salinity of spray-dried chitosan/acid/NaCl microparticles were tested to ensure a low-sodium and high-salinity salty agent. The spray-dried chitosan/acid/NaCl microparticles were hollow and had a favourable hygroscopicity, and increased NaCl content and decreased organic acid content. Their size of the microparticles was 15.4-32.0μm and increased with NaCl concentration. The microparticles of acetic and lactic acid groups had a NaCl crystal size of 1-2 and 1-4μm, respectively. The NaCl crystals of acetic, lactic and citric acid group microparticles were distributed on the microparticle matrices, mostly on the microparticle surface and mainly on the inner walls of the microparticles walls, respectively. The acetic and lactic acid group microparticles were relatively smaller than general salt, with NaCl crystals distributed on the particle surfaces. Consequently, they were perceived as saltier than general salt and could potentially be regarded as a low-sodium salt for surface-salted foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

21 CFR 582.7724 - Sodium alginate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Sodium alginate. 582.7724 Section 582.7724 Food... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Stabilizers § 582.7724 Sodium alginate. (a) Product. Sodium alginate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 582.7724 - Sodium alginate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sodium alginate. 582.7724 Section 582.7724 Food... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Stabilizers § 582.7724 Sodium alginate. (a) Product. Sodium alginate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 582.7724 - Sodium alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium alginate. 582.7724 Section 582.7724 Food... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Stabilizers § 582.7724 Sodium alginate. (a) Product. Sodium alginate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 582.7724 - Sodium alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Sodium alginate. 582.7724 Section 582.7724 Food... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Stabilizers § 582.7724 Sodium alginate. (a) Product. Sodium alginate. (b) Conditions of use. This substance is generally recognized as...

21 CFR 582.7724 - Sodium alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium alginate. 582.7724 Section 582.7724 Food... DRUGS, FEEDS, AND RELATED PRODUCTS SUBSTANCES GENERALLY RECOGNIZED AS SAFE Stabilizers § 582.7724 Sodium alginate. (a) Product. Sodium alginate. (b) Conditions of use. This substance is generally recognized as...

Marathon running increases circulating endothelial- and thrombocyte-derived microparticles.

PubMed

Schwarz, Viktoria; Düsing, Philip; Liman, Thomas; Werner, Christian; Herm, Juliane; Bachelier, Katrin; Krüll, Matthias; Brechtel, Lars; Jungehulsing, Gerhard J; Haverkamp, Wilhelm; Böhm, Michael; Endres, Matthias; Haeusler, Karl Georg; Laufs, Ulrich

2018-02-01

Background Acute vascular effects of high intensity physical activity are incompletely characterized. Circulating microparticles are cellular markers for vascular activation and damage. Methods Microparticles were analysed in 99 marathon runners (49 ± 6 years, 22% female) of the prospective Berlin Beat of Running study. Blood samples were taken within three days before, immediately after and within two days after the marathon run. Endothelial-derived microparticles were labelled with CD144, CD31 and CD62E, platelet-derived microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45 and monocyte-derived microparticles with CD14. Results Marathon running induced leukocytosis (5.9 ± 0.1 to 14.8 ± 0.3 10 9 /l, p < 0.0001) and increased platelet counts (239 ± 4.6 to 281 ± 5.9 10 9 /l, p < 0.0001) immediately after the marathon. Blood monocytes increased and lymphocytes decreased after the run ( p < 0.0001). Endothelial-derived microparticles were acutely increased ( p = 0.008) due to a 23% increase of apoptotic endothelial-derived microparticles ( p = 0.007) and returned to baseline within two days after the marathon. Thrombocyte-derived microparticles acutely increased by 38% accompanied by an increase in activated and apoptotic thrombocyte-derived microparticles ( p ≤ 0.0001) each. Both monocyte- and leukocyte-derived microparticles were decreased immediately after marathon run ( p < 0.0001) and remained below baseline until day 2. Troponin T increased from 12 to 32 ng/l ( p < 0.0001) immediately after the run and returned to baseline after two days. Conclusion Circulating apoptotic endothelial- and thrombocyte-derived microparticles increased after marathon running consistent with an acute pro-thrombotic and pro-inflammatory state. Exercise-induced vascular damage reflected by microparticles could indicate potential mechanisms of post-exertional cardiovascular complications. Further studies are warranted to investigate microparticles as markers to identify individuals prone to such complications.

Phagocytosis of microparticles by alveolar macrophages during acute lung injury requires MerTK.

PubMed

Mohning, Michael P; Thomas, Stacey M; Barthel, Lea; Mould, Kara J; McCubbrey, Alexandria L; Frasch, S Courtney; Bratton, Donna L; Henson, Peter M; Janssen, William J

2018-01-01

Microparticles are a newly recognized class of mediators in the pathophysiology of lung inflammation and injury, but little is known about the factors that regulate their accumulation and clearance. The primary objective of our study was to determine whether alveolar macrophages engulf microparticles and to elucidate the mechanisms by which this occurs. Alveolar microparticles were quantified in bronchoalveolar fluid of mice with lung injury induced by LPS and hydrochloric acid. Microparticle numbers were greatest at the peak of inflammation and declined as inflammation resolved. Isolated, fluorescently labeled particles were placed in culture with macrophages to evaluate ingestion in the presence of endocytosis inhibitors. Ingestion was blocked with cytochalasin D and wortmannin, consistent with a phagocytic process. In separate experiments, mice were treated intratracheally with labeled microparticles, and their uptake was assessed though microscopy and flow cytometry. Resident alveolar macrophages, not recruited macrophages, were the primary cell-ingesting microparticles in the alveolus during lung injury. In vitro, microparticles promoted inflammatory signaling in LPS primed epithelial cells, signifying the importance of microparticle clearance in resolving lung injury. Microparticles were found to have phosphatidylserine exposed on their surfaces. Accordingly, we measured expression of phosphatidylserine receptors on macrophages and found high expression of MerTK and Axl in the resident macrophage population. Endocytosis of microparticles was markedly reduced in MerTK-deficient macrophages in vitro and in vivo. In conclusion, microparticles are released during acute lung injury and peak in number at the height of inflammation. Resident alveolar macrophages efficiently clear these microparticles through MerTK-mediated phagocytosis.

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

PubMed

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-11-01

Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and endothelial microparticles could be an important immunmodulatory therapeutic target.

Endothelial- and Platelet-Derived Microparticles Are Generated During Liver Resection in Humans.

PubMed

Banz, Yara; Item, Gian-Marco; Vogt, Andreas; Rieben, Robert; Candinas, Daniel; Beldi, Guido

2016-01-01

Cell-derived plasma microparticles (<1.5 μm) originating from various cell types have the potential to regulate thrombogenesis and inflammatory responses. The aim of this study was to test the hypothesis that microparticles generated during hepatic surgery co-regulate postoperative procoagulant and proinflammatory events. In 30 patients undergoing liver resection, plasma microparticles were isolated, quantitated, and characterized as endothelial (CD31+, CD41-), platelet (CD41+), or leukocyte (CD11b+) origin by flow cytometry and their procoagulant and proinflammatory activity was measured by immunoassays. During liver resection, the total numbers of microparticles increased with significantly more Annexin V-positive, endothelial and platelet-derived microparticles following extended hepatectomy compared to standard and minor liver resections. After liver resection, microparticle tissue factor and procoagulant activity increased along with overall coagulation as assessed by thrombelastography. Levels of leukocyte-derived microparticles specifically increased in patients with systemic inflammation as assessed by C-reactive protein but are independent of the extent of liver resection. Endothelial and platelet-derived microparticles are specifically elevated during liver resection, accompanied by increased procoagulant activity. Leukocyte-derived microparticles are a potential marker for systemic inflammation. Plasma microparticles may represent a specific response to surgical stress and may be an important mediator of postoperative coagulation and inflammation.

Particulate matter induces prothrombotic microparticle shedding by human mononuclear and endothelial cells.

PubMed

Neri, Tommaso; Pergoli, Laura; Petrini, Silvia; Gravendonk, Lotte; Balia, Cristina; Scalise, Valentina; Amoruso, Angela; Pedrinelli, Roberto; Paggiaro, Pierluigi; Bollati, Valentina; Celi, Alessandro

2016-04-01

Particulate airborne pollution is associated with increased cardiopulmonary morbidity. Microparticles are extracellular vesicles shed by cells upon activation or apoptosis involved in physiological processes such as coagulation and inflammation, including airway inflammation. We investigated the hypothesis that particulate matter causes the shedding of microparticles by human mononuclear and endothelial cells. Cells, isolated from the blood and the umbilical cords of normal donors, were cultured in the presence of particulate from a standard reference. Microparticles were assessed in the supernatant as phosphatidylserine concentration. Microparticle-associated tissue factor was assessed by an one-stage clotting assay. Nanosight technology was used to evaluate microparticle size distribution. Particulate matter induces a dose- and time- dependent, rapid (1h) increase in microparticle generation in both cells. These microparticles express functional tissue factor. Particulate matter increases intracellular calcium concentration and phospholipase C inhibition reduces microparticle generation. Nanosight analysis confirmed that upon exposure to particulate matter both cells express particles with a size range consistent with the definition of microparticles (50-1000 nm). Exposure of mononuclear and endothelial cells to particulate matter upregulates the generation of microparticles at least partially mediated by calcium mobilization. This observation might provide a further link between airborne pollution and cardiopulmonary morbidity. Copyright © 2016 Elsevier B.V. All rights reserved.

Antibacterial Performance of Alginic Acid Coating on Polyethylene Film

PubMed Central

Karbassi, Elika; Asadinezhad, Ahmad; Lehocký, Marian; Humpolíček, Petr; Vesel, Alenka; Novák, Igor; Sáha, Petr

2014-01-01

Alginic acid coated polyethylene films were examined in terms of surface properties and bacteriostatic performance against two most representative bacterial strains, that is, Escherichia coli and Staphylococcus aureus. Microwave plasma treatment followed by brush formation in vapor state from three distinguished precursors (allylalcohol, allylamine, hydroxyethyl methacrylate) was carried out to deposit alginic acid on the substrate. Surface analyses via various techniques established that alginic acid was immobilized onto the surface where grafting (brush) chemistry influenced the amount of alginic acid coated. Moreover, alginic acid was found to be capable of bacterial growth inhibition which itself was significantly affected by the brush type. The polyanionic character of alginic acid as a carbohydrate polymer was assumed to play the pivotal role in antibacterial activity. The cell wall composition of two bacterial strains along with the substrates physicochemical properties accounted for different levels of bacteriostatic performance. PMID:25196604

Development of PVA-alginate as a matrix for enzymatic decolorization of textile dye in bioreactor system

NASA Astrophysics Data System (ADS)

Yanto, Dede Heri Yuli; Zahara, Syifa; Laksana, Raden Permana Budi; Anita, Sita Heris; Oktaviani, Maulida; Sari, Fahriya Puspita

2017-01-01

An immobilization technique using polyvinyl alcohol (PVA) crosslinked with sodium alginate as a matrix has been developed for textile dyes decolorization. Textiles use dye as an addition to the aesthetic value of the product. Dyes are generally used is a textile dye where the waste will be released directly into the waters around 2-20%. Therefore, it is important to develop an enzyme immobilization method using PVA-Alginate as a matrix. Based on the results of the study showed that the PVA-Alginate beads produced high decolorization percent compared to beads which contains only Ca-alginate alone and formula matrix is optimum at PVA 6% and alginate 1.5%. Encapsulation with boric acid at 7% showed optimum decolorization and reduction for enzyme leakage during decolorization. This study suggested that immobilization of enzymes into PVA-alginate matrix might be used as a biodecolorating agent.

21 CFR 172.858 - Propylene glycol alginate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Propylene glycol alginate. 172.858 Section 172.858... Propylene glycol alginate. The food additive propylene glycol alginate (CAS Reg. No. 9005-37-2) may be used... the act: (1) The name of the additive, “propylene glycol alginate” or “propylene glycol ester of...

Fabrication of cell-benign inverse opal hydrogels for three-dimensional cell culture.

PubMed

Im, Pilseon; Ji, Dong Hwan; Kim, Min Kyung; Kim, Jaeyun

2017-05-15

Inverse opal hydrogels (IOHs) for cell culture were fabricated and optimized using calcium-crosslinked alginate microbeads as sacrificial template and gelatin as a matrix. In contrast to traditional three-dimensional (3D) scaffolds, the gelatin IOHs allowed the utilization of both the macropore surface and inner matrix for cell co-culture. In order to remove templates efficiently for the construction of 3D interconnected macropores and to maintain high cell viability during the template removal process using EDTA solution, various factors in fabrication, including alginate viscosity, alginate concentration, alginate microbeads size, crosslinking calcium concentration, and gelatin network density were investigated. Low viscosity alginate, lower crosslinking calcium ion concentration, and lower concentration of alginate and gelatin were found to obtain high viability of cells encapsulated in the gelatin matrix after removal of the alginate template by EDTA treatment by allowing rapid dissociation and diffusion of alginate polymers. Based on the optimized fabrication conditions, gelatin IOHs showed good potential as a cell co-culture system, applicable to tissue engineering and cancer research. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantification of alginate by aggregation induced by calcium ions and fluorescent polycations.

PubMed

Zheng, Hewen; Korendovych, Ivan V; Luk, Yan-Yeung

2016-01-01

For quantification of polysaccharides, including heparins and alginates, the commonly used carbazole assay involves hydrolysis of the polysaccharide to form a mixture of UV-active dye conjugate products. Here, we describe two efficient detection and quantification methods that make use of the negative charges of the alginate polymer and do not involve degradation of the targeted polysaccharide. The first method utilizes calcium ions to induce formation of hydrogel-like aggregates with alginate polymer; the aggregates can be quantified readily by staining with a crystal violet dye. This method does not require purification of alginate from the culture medium and can measure the large amount of alginate that is produced by a mucoid Pseudomonas aeruginosa culture. The second method employs polycations tethering a fluorescent dye to form suspension aggregates with the alginate polyanion. Encasing the fluorescent dye in the aggregates provides an increased scattering intensity with a sensitivity comparable to that of the conventional carbazole assay. Both approaches provide efficient methods for monitoring alginate production by mucoid P. aeruginosa. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of setting time and flow properties of self-synthesize alginate impressions

NASA Astrophysics Data System (ADS)

Halim, Calista; Cahyanto, Arief; Sriwidodo, Harsatiningsih, Zulia

2018-02-01

Alginate is an elastic hydrocolloid dental impression materials to obtain negative reproduction of oral mucosa such as to record soft-tissue and occlusal relationships. The aim of the present study was to synthesize alginate and to determine the setting time and flow properties. There were five groups of alginate consisted of fifty samples self-synthesize alginate and commercial alginate impression product. Fifty samples were divided according to two tests, each twenty-five samples for setting time and flow test. Setting time test was recorded in the s unit, meanwhile, flow test was recorded in the mm2 unit. The fastest setting time result was in the group three (148.8 s) and the latest was group fours). The highest flow test result was in the group three (69.70 mm2) and the lowest was group one (58.34 mm2). Results were analyzed statistically by one way ANOVA (α= 0.05), showed that there was a statistical significance of setting time while no statistical significance of flow properties between self-synthesize alginate and alginate impression product. In conclusion, the alginate impression was successfully self-synthesized and variation composition gives influence toward setting time and flow properties. The most resemble setting time of control group is group three. The most resemble flow of control group is group four.

Review: peripheral nerve regeneration using non-tubular alginate gel crosslinked with covalent bonds.

PubMed

Hashimoto, Tadashi; Suzuki, Yoshihisa; Suzuki, Kyoko; Nakashima, Toshihide; Tanihara, Masao; Ide, Chizuka

2005-06-01

We have developed a nerve regeneration material consisting of alginate gel crosslinked with covalent bonds. in the first part of this study, we attempted to analyze nerve regeneration through alginate gel in the early stages within 2 weeks. in the second part, we tried to regenerate cat peripheral nerve by using alginate tubular or non-tubular nerve regeneration devices, and compared their efficacies. Four days after surgery, regenerating axons grew without Schwann cell investment through the partially degraded alginate gel, being in direct contact with the alginate without a basal lamina covering. One to 2 weeks after surgery, regenerating axons were surrounded by common Schwann cells, forming small bundles, with some axons at the periphery being partly in direct contact with alginate. At the distal stump, numerous Schwann cells had migrated into the alginate 8-14 days after surgery. Remarkable restorations of the 50-mm gap in cat sciatic nerve were obtained after a long term by using tubular or non-tubular nerve regeneration material consisting mainly of alginate gel. However, there was no significant difference between both groups at electrophysiological and morphological evaluation. Although, nowadays, nerve regeneration materials being marketed mostly have a tubular structure, our results suggest that the tubular structure is not indispensable for peripheral nerve regeneration.

Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.

PubMed

Li, Ze; Xiong, Fangfang; He, Jintian; Dai, Xiaojing; Wang, Gaizhen

2016-12-01

In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg. Copyright © 2016. Published by Elsevier B.V.

Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect.

PubMed

Mantripragada, Venkata P; Jayasuriya, Ambalangodage C

2016-06-01

Injectable chitosan microparticles were prepared using a simple coacervation method under physiologically friendly conditions by eliminating oil or toxic chemical, and employing low temperature and pressure for growth factor stability. Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the chitosan microparticles by two methods: encapsulating and coating techniques. These microparticles were tested in vivo to determine the biological response in a rat femoral bone defect at 6 and 12 weeks. Four groups (n=10) were tested which include two groups for BMP-7 incorporated microparticles (by two techniques), microparticles without BMP-7, and defect itself (negative control). Healthy bone formation was observed around the microparticles, which were only confined to the defect site and did not disperse. Histology indicated minor inflammatory response around the microparticles at 6 weeks, which reduced by 12 weeks. Micro-CT analysis of bone surface density and porosity was found to be significantly more (p<0.05) for microparticles containing groups, in comparison with controls, which suggests that the new bone formed in the presence of microparticles is more interconnected and porous. Collagen fibrils analysis conducted using multiphoton microscopy showed significant improvement in the formation of bundled collagen area (%) in microparticles containing groups in comparison with controls, indicating higher cross-linking between the fibrils. Microparticles were biocompatible and did not degrade in the 12 week implant period. Copyright © 2016 Elsevier B.V. All rights reserved.

Thalassemic erythrocytes release microparticles loaded with hemichromes by redox activation of p72Syk kinase.

PubMed

Ferru, Emanuela; Pantaleo, Antonella; Carta, Franco; Mannu, Franca; Khadjavi, Amina; Gallo, Valentina; Ronzoni, Luisa; Graziadei, Giovanna; Cappellini, Maria Domenica; Turrini, Francesco

2014-03-01

High counts of circulating microparticles, originated from the membrane of abnormal erythrocytes, have been associated with increased thrombotic risk in hemolytic disorders. Our studies indicate that in thalassemia intermedia patients the number of circulating microparticles correlates with the capability of the thalassemic erythrocytes to release microparticles. The microparticles are characteristically loaded with hemichromes formed by denatured α-chains. This finding was substantiated by the positive correlation observed in thalassemia intermedia patients between the amount of hemichromes measured in erythrocytes, their capability to release microparticles and the levels of plasma hemichromes. We observed that hemichromes, following their binding to the cytoplasmic domain of band 3, induce the formation of disulfide band 3 dimers that are subsequently phosphorylated by p72Syk kinase. Phosphorylation of oxidized band 3 appears to be relevant for the formation of large hemichromes/band 3 clusters that, in turn, induce local membrane instability and the release of microparticles. Proteomic analysis of microparticles released from thalassemia intermedia erythrocytes indicated that, besides hemichromes and clustered band 3, the microparticles contain a characteristic set of proteins that includes catalase, heat shock protein 70, peroxiredoxin 2 and carbonic anhydrase. High amounts of immunoglobulins and C3 have also been found to be associated with microparticles, accounting for their intense phagocytosis. The effect of p72Syk kinase inhibitors on the release of microparticles from thalassemia intermedia erythrocytes may indicate new perspectives for controlling the release of circulating microparticles in hemolytic anemias.

Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/ Rho kinase pathways targeted to lipid rafts.

PubMed

Burger, Dylan; Montezano, Augusto C; Nishigaki, Nobuhiro; He, Ying; Carter, Anthony; Touyz, Rhian M

2011-08-01

Circulating microparticles are increased in cardiovascular disease and may themselves promote oxidative stress and inflammation. Molecular mechanisms underlying their formation and signaling are unclear. We investigated the role of reactive oxygen species (ROS), Rho kinase, and lipid rafts in microparticle formation and examined their functional significance in endothelial cells (ECs). Microparticle formation from angiotensin II (Ang II)-stimulated ECs and apolipoprotein E(-/-) mice was assessed by annexin V or by CD144 staining and electron microscopy. Ang II promoted microparticle formation and increased EC O(2)(-) generation and Rho kinase activity. Ang II-stimulated effects were inhibited by irbesartan (Ang II receptor type I blocker) and fasudil (Rho kinase inhibitor). Methyl-β-cyclodextrin and nystatin, which disrupt lipid rafts/caveolae, blocked microparticle release. Functional responses, assessed in microparticle-stimulated ECs, revealed increased O(2)(-) production, enhanced vascular cell adhesion molecule/platelet-EC adhesion molecule expression, and augmented macrophage adhesion. Inhibition of epidermal growth factor receptor blocked the prooxidative and proinflammatory effects of microparticles. In vitro observations were confirmed in apolipoprotein E(-/-) mice, which displayed vascular inflammation and high levels of circulating endothelial microparticles, effects that were reduced by apocynin. We demonstrated direct actions of Ang II on endothelial microparticle release, mediated through NADPH oxidase, ROS, and Rho kinase targeted to lipid rafts. Microparticles themselves stimulated endothelial ROS formation and inflammatory responses. Our findings suggest a feedforward system whereby Ang II promotes EC injury through its own endothelial-derived microparticles.

Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.

PubMed

Yang, Hae Kyung; Ham, Dong-Sik; Park, Heon-Seok; Rhee, Marie; You, Young Hye; Kim, Min Jung; Shin, Juyoung; Kim, On-You; Khang, Gilson; Hong, Tae Ho; Kim, Ji-Won; Lee, Seung-Hwan; Cho, Jae-Hyoung; Yoon, Kun-Ho

2016-02-01

Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules. Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants. The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P < 0.001) compared to that of alginate capsules up to 1 year after transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation. The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.

Production and characterization of the healthy brown rice milk with sodium alginate addition from brown algae Sargassum binderi as emulsifier

NASA Astrophysics Data System (ADS)

Latifah, R. N.; Warganegara, F. M.

2018-03-01

Brown rice milk, a plant milk, is potential to cure beriberi disease. Alginate was used as an emulsifier and increased the nutrition of brown rice milk. Alginate from Sargassum binderi was extracted by nonacidic treatment. The yield of alginate was 6.25 %. The moisture and water content of alginate were 18.27 % and 12.2 %, respectively. The density and viscosity of 0.1 % alginates in aqueous solution were 1.007 g·mL-1 and 7.651 × 10-3 kg·m-1s-1, respectively. The characteristics peaks of alginate appeared at 3,477; 1,633 and 1,419 cm-1, corresponding to hydroxyl (OH), carbonyl (C=O) and carboxyl (COOH), respectively. The best composition of alginate addition in brown rice milk was 0.2 %. The viscosity of the 0.2 % alginate in brown rice milk was 1.206 × 10-2 kg·m-1s-1 and showed a texture of small particle with closer spaces between the particles. The addition of alginate in brown rice milk also inhibited the process of sedimentation of milk which showed in the first order. The nutrition composition of the best brown rice milk was 40.21 mg·mL-1 carbohydrate; 1.3 mg·mL-1 protein; 0.158 mg·mL-1 fat and 13.1 mg·mL-1 total dietary fiber.

Injectable MMP-sensitive alginate hydrogels as hMSC delivery systems.

PubMed

Fonseca, Keila B; Gomes, David B; Lee, Kangwon; Santos, Susana G; Sousa, Aureliana; Silva, Eduardo A; Mooney, David J; Granja, Pedro L; Barrias, Cristina C

2014-01-13

Hydrogels with the potential to provide minimally invasive cell delivery represent a powerful tool for tissue-regeneration therapies. In this context, entrapped cells should be able to escape the matrix becoming more available to actively participate in the healing process. Here, we analyzed the performance of proteolytically degradable alginate hydrogels as vehicles for human mesenchymal stem cells (hMSC) transplantation. Alginate was modified with the matrix metalloproteinase (MMP)-sensitive peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG), which did not promote dendritic cell maturation in vitro, neither free nor conjugated to alginate chains, indicating low immunogenicity. hMSC were entrapped within MMP-sensitive and MMP-insensitive alginate hydrogels, both containing cell-adhesion RGD peptides. Softer (2 wt % alginate) and stiffer (4 wt % alginate) matrices were tested. When embedded in a Matrigel layer, hMSC-laden MMP-sensitive alginate hydrogels promoted more extensive outward cell migration and invasion into the tissue mimic. In vivo, after 4 weeks of subcutaneous implantation in a xenograft mouse model, hMSC-laden MMP-sensitive alginate hydrogels showed higher degradation and host tissue invasion than their MMP-insensitive equivalents. In both cases, softer matrices degraded faster than stiffer ones. The transplanted hMSC were able to produce their own collagenous extracellular matrix, and were located not only inside the hydrogels, but also outside, integrated in the host tissue. In summary, injectable MMP-sensitive alginate hydrogels can act as localized depots of cells and confer protection to transplanted cells while facilitating tissue regeneration.

Preferential localization of Lactococcus lactis cells entrapped in a caseinate/alginate phase separated system.

PubMed

Léonard, Lucie; Gharsallaoui, Adem; Ouaali, Fahima; Degraeve, Pascal; Waché, Yves; Saurel, Rémi; Oulahal, Nadia

2013-09-01

This study aimed to entrap bioprotective lactic acid bacteria in a sodium caseinate/sodium alginate aqueous two-phase system. Phase diagram at pH=7 showed that sodium alginate and sodium caseinate were not miscible when their concentrations exceeded 1% (w/w) and 6% (w/w), respectively. The stability of the caseinate/alginate two-phase system was also checked at pH values of 6.0 and 5.5. Lactococcus lactis subsp. lactis LAB3 cells were added in a 4% (w/w) caseinate/1.5% (w/w) alginate two-phase system at pH=7. Fluorescence microscopy allowed to observe that the caseinate-rich phase formed droplets dispersed in a continuous alginate-rich phase. The distribution of bacteria in such a system was observed by epifluorescence microscopy: Lc. lactis LAB3 cells stained with Live/Dead(®) Baclight kit™ were located exclusively in the protein phase. Since zeta-potential measurements indicated that alginate, caseinate and bacterial cells all had an overall negative charge at pH 7, the preferential adhesion of LAB cells was assumed to be driven by hydrophobic effect or by depletion phenomena in such biopolymeric systems. Moreover, LAB cells viability was significantly higher in the ternary mixture obtained in the presence of both caseinate and alginate than in single alginate solution. Caseinate/alginate phase separated systems appeared thus well suited for Lc. lactis LAB3 cells entrapment. Copyright © 2013 Elsevier B.V. All rights reserved.

Three-dimensional bioprinting of complex cell laden alginate hydrogel structures.

PubMed

Tabriz, Atabak Ghanizadeh; Hermida, Miguel A; Leslie, Nicholas R; Shu, Wenmiao

2015-12-21

Different bioprinting techniques have been used to produce cell-laden alginate hydrogel structures, however these approaches have been limited to 2D or simple three-dimension (3D) structures. In this study, a new extrusion based bioprinting technique was developed to produce more complex alginate hydrogel structures. This was achieved by dividing the alginate hydrogel cross-linking process into three stages: primary calcium ion cross-linking for printability of the gel, secondary calcium cross-linking for rigidity of the alginate hydrogel immediately after printing and tertiary barium ion cross-linking for long-term stability of the alginate hydrogel in culture medium. Simple 3D structures including tubes were first printed to ensure the feasibility of the bioprinting technique and then complex 3D structures such as branched vascular structures were successfully printed. The static stiffness of the alginate hydrogel after printing was 20.18 ± 1.62 KPa which was rigid enough to sustain the integrity of the complex 3D alginate hydrogel structure during the printing. The addition of 60 mM barium chloride was found to significantly extend the stability of the cross-linked alginate hydrogel from 3 d to beyond 11 d without compromising the cellular viability. The results based on cell bioprinting suggested that viability of U87-MG cells was 93 ± 0.9% immediately after bioprinting and cell viability maintained above 88% ± 4.3% in the alginate hydrogel over the period of 11 d.

Strategies to overcome pH-dependent solubility of weakly basic drugs by using different types of alginates.

PubMed

Gutsche, S; Krause, M; Kranz, H

2008-12-01

Weakly basic drugs demonstrate higher solubility at lower pH, thus often leading to faster drug release at lower pH. The objective of this study was to achieve pH-independent release of weakly basic drugs from extended release formulations based on the naturally occurring polymer sodium alginate. Three approaches to overcome the pH-dependent solubility of the weakly basic model drug verapamil hydrochloride were investigated. First, matrix tablets were prepared by direct compression of drug substance with different types of sodium alginate only. Second, pH-modifiers were added to the drug/alginate matrix systems. Third, press-coated tablets consisting of an inner pH-modifier tablet core and an outer drug/sodium alginate coat were prepared. pH-Independent drug release was achieved from matrix tablets consisting of selected alginates and drug substance only. Alginates are better soluble at higher pH. Therefore, they are able to compensate the poor solubility of weakly basic drugs at higher pH as the matrix of the tablets dissolves faster. This approach was successful when using alginates that demonstrated fast hydration and erosion at higher pH. The approach failed for alginates with less-pronounced erosion at higher pH. The addition of fumaric acid to drug/alginate-based matrix systems decreased the microenvironmental pH within the tablets thus increasing the solubility of the weakly basic drug at higher pH. Therefore, pH-independent drug release was achieved irrespective of the type of alginate used. Drug release from press-coated tablets did not provide any further advantages as compound release remained pH-dependent.

In Vitro Human Umbilical Vein Endothelial Cells Response to Ionic Dissolution Products from Lithium-Containing 45S5 Bioactive Glass

PubMed Central

Haro Durand, Luis A.; Vargas, Gabriela E.; Vera-Mesones, Rosa; Baldi, Alberto; Zago, María P.; Fanovich, María A.; Boccaccini, Aldo R.; Gorustovich, Alejandro

2017-01-01

Since lithium (Li+) plays roles in angiogenesis, the localized and controlled release of Li+ ions from bioactive glasses (BGs) represents a promising alternative therapy for the regeneration and repair of tissues with a high degree of vascularization. Here, microparticles from a base 45S5 BG composition containing (wt %) 45% SiO2, 24.5% Na2O, 24.5% CaO, and 6% P2O5, in which Na2O was partially substituted by 5% Li2O (45S5.5Li), were obtained. The results demonstrate that human umbilical vein endothelial cells (HUVECs) have greater migratory and proliferative response and ability to form tubules in vitro after stimulation with the ionic dissolution products (IDPs) of the 45S5.5Li BG. The results also show the activation of the canonical Wnt/β-catenin pathway and the increase in expression of proangiogenic cytokines insulin like growth factor 1 (IGF1) and transforming growth factor beta (TGFβ). We conclude that the IDPs of 45S5.5Li BG would act as useful inorganic agents to improve tissue repair and regeneration, ultimately stimulating HUVECs behavior in the absence of exogenous growth factors. PMID:28773103

Stagnation point flow of wormlike micellar solutions in a microfluidic cross-slot device: effects of surfactant concentration and ionic environment.

PubMed

Haward, Simon J; McKinley, Gareth H

2012-03-01

We employ the techniques of microparticle image velocimetry and full-field birefringence microscopy combined with mechanical measurements of the pressure drop to perform a detailed characterization of the extensional rheology and elastic flow instabilities observed for a range of wormlike micellar solutions flowing through a microfluidic cross-slot device. As the flow rate through the device is increased, the flow first bifurcates from a steady symmetric to a steady asymmetric configuration characterized by a birefringent strand of highly aligned micellar chains oriented along the shear-free centerline of the flow field. At higher flow rates the flow becomes three dimensional and time dependent and is characterized by aperiodic spatiotemporal fluctuations of the birefringent strand. The extensional properties and critical conditions for the onset of flow instabilities in the fluids are highly dependent on the fluid formulation (surfactant concentration and ionic strength) and the resulting changes in the linear viscoelasticity and nonlinear shear rheology of the fluids. By combining the measurements of critical conditions for the flow transitions with the viscometric material properties and the degree of shear-thinning characterizing each test fluid, it is possible to construct a stability diagram for viscoelastic flow of complex fluids in the cross-slot geometry.

Influence of hydrophobic modification in alginate-based hydrogels for biomedical applications

NASA Astrophysics Data System (ADS)

Choudhary, Soumitra

Alginate has been exploited commercially for decades in foods, textiles, paper, pharmaceutical industries, and also as a detoxifier for removing heavy metals. Alginate is also popular in cell encapsulation because of its relatively mild gelation protocol and simple chemistry with which biological active entities can be immobilized. Surface modification of alginate gels has been explored to induce desired cell interactions with the gel matrix. These modifications alter the bulk properties, which strongly determine on how cells feel and response to the three-dimensional microenvironment. However, there is a need to develop strategies to engineer functionalities into bulk alginate hydrogels that not only preserve their inherent qualities but are also less toxic. In this thesis, our main focus was to optimize the mechanical properties of alginate-based hydrogels, and by doing so control the performance of the biomaterials. In the first scheme, we used alginate and hydrophobically modified ethyl hydroxy ethyl cellulose as components in interpenetrating polymer network (IPN) gels. The second network was used to control gelation time and rheological properties. We believe these experiments also may provide insight into the mechanical and structural properties of more complex biopolymer gels and naturally-occurring IPNs. Next, we worked on incorporating a hydrophobic moiety directly into the alginate chain, resulting in materials for extended release of hydrophobic drugs. We successfully synthesized hydrophobically modified alginate (HMA) by attaching octylamine groups onto the alginate backbone by standard carbodiimide based amide coupling reaction. Solubility of several model hydrophobic drugs in dilute HMA solutions was found to be increased by more than an order of magnitude. HMA hydrogels, prepared by crosslinking the alginate chains with calcium ions, were found to exhibit excellent mechanical properties (modulus ˜100 kPa) with release extended upto 5 days. Ability to vary the hydrophobic tails, degree of substitution, and crosslinker density gave us handles to tune the properties of the materials. Finally we will show how modulus of the alginate gels can be used to influence the proliferation and differentiation of encapsulated neural stem cells. A preliminary attempt was also made to develop three dimensional "life-like" vasculature network made from alginate tubes and other biomaterials.

Intracellular origin and ultrastructure of platelet-derived microparticles.

PubMed

Ponomareva, A A; Nevzorova, T A; Mordakhanova, E R; Andrianova, I A; Rauova, L; Litvinov, R I; Weisel, J W

2017-08-01

Essentials Platelet microparticles play a major role in pathologies, including hemostasis and thrombosis. Platelet microparticles have been analyzed and classified based on their ultrastructure. The structure and intracellular origin of microparticles depend on the cell-activating stimulus. Thrombin-treated platelets fall apart and form microparticles that contain cellular organelles. Background Platelet-derived microparticles comprise the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the (patho)physiological roles of platelet-derived microparticles, mechanisms of their formation and structural details remain largely unknown. Objectives Here we studied the formation, ultrastructure and composition of platelet-derived microparticles from isolated human platelets, either quiescent or stimulated with one of the following activators: arachidonic acid, ADP, collagen, thrombin or calcium ionophore A23187. Methods Using flow cytometry, transmission and scanning electron microscopy, we analyzed the intracellular origin, structural diversity and size distributions of the subcellular particles released from platelets. Results The structure, dimensions and intracellular origin of microparticles depend on the cell-activating stimulus. The main structural groups include a vesicle surrounded by one thin membrane or multivesicular structures. Thrombin, unlike other stimuli, induced formation of microparticles not only from the platelet plasma membrane and cytoplasm but also from intracellular structures. A fraction of these vesicular particles having an intracellular origin contained organelles, such as mitochondria, glycogen granules and vacuoles. The size of platelet-derived microparticles depended on the nature of the cell-activating stimulus. Conclusion The results obtained provide a structural basis for the qualitative differences of various platelet activators, for specific physiological and pathological effects of microparticles, and for development of advanced assays. © 2017 International Society on Thrombosis and Haemostasis.

Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases

PubMed Central

Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

2009-01-01

Background Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Design and Methods Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Results Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-α) and also induced allogeneic naive CD4+ T cells to proliferate and to produce type 1 cytokines such as interferon-γ and tumor necrosis factor-α. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Conclusions Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and endothelial microparticles could be an important immunmodulatory therapeutic target. PMID:19648164

Circulating levels of cell-derived microparticles are reduced by mild hypobaric hypoxia: data from a randomised controlled trial.

PubMed

Ayers, Lisa; Stoewhas, Anne-Christin; Ferry, Berne; Latshang, Tsogyal D; Lo Cascio, Christian M; Sadler, Ross; Stadelmann, Katrin; Tesler, Noemi; Huber, Reto; Achermann, Peter; Bloch, Konrad E; Kohler, Malcolm

2014-05-01

Hypoxia is known to induce the release of microparticles in vitro. However, few publications have addressed the role of hypoxia in vivo on circulating levels of microparticles. This randomised, controlled, crossover trial aimed to determine the effect of mild hypoxia on in vivo levels of circulating microparticles in healthy individuals. Blood was obtained from 51 healthy male volunteers (mean age of 26.9 years) at baseline altitude (490 m) and after 24 and 48 h at moderate altitude (2,590 m). The order of altitude exposure was randomised. Flow cytometry was used to assess platelet-poor plasma for levels of circulating microparticles derived from platelets, endothelial cells, leucocytes, granulocytes, monocytes, red blood cells and procoagulant microparticles. Mean (standard deviation) oxygen saturation was significantly lower on the first and second day after arrival at 2,590 m, 91.0 (2.0) and 92.0 (2.0) %, respectively, compared to 490 m, 96 (1.0) %, p < 0.001 for both comparisons. A significant decrease in the levels of procoagulant microparticles (annexin V+ -221/μl 95 % CI -370.8/-119.0, lactadherin+ -202/μl 95 % CI -372.2/-93.1), platelet-derived microparticles (-114/μl 95 % CI -189.9/-51.0) and red blood cell-derived microparticles (-81.4 μl 95 % CI -109.9/-57.7) after 48 h at moderate altitude was found. Microparticles derived from endothelial cells, granulocytes, monocytes and leucocytes were not significantly altered by exposure to moderate altitude. In healthy male individuals, mild hypobaric hypoxia, induced by a short-term stay at moderate altitude, is associated with lower levels of procoagulant microparticles, platelet-derived microparticles and red blood cell-derived microparticles, suggesting a reduction in thrombotic potential.

Microparticles variability in fresh frozen plasma: preparation protocol and storage time effects

PubMed Central

Kriebardis, Anastasios G.; Antonelou, Marianna H.; Georgatzakou, Hara T.; Tzounakas, Vassilis L.; Stamoulis, Konstantinos E.; Papassideri, Issidora S.

2016-01-01

Background Extracellular vesicles or microparticles exhibiting procoagulant and thrombogenic activity may contribute to the haemostatic potential of fresh frozen plasma. Materials and methods Fresh frozen plasma was prepared from platelet-rich plasma at 20 °C (Group-1 donors) or directly from whole blood at 4 °C (Group-2 donors). Each unit was aseptically divided into three parts, stored frozen for specific periods of time, and analysed by flow cytometry for procoagulant activity immediately after thaw or following post-thaw storage for 24 h at 4 °C. Donors’ haematologic, biochemical and life-style profiles as well as circulating microparticles were analysed in parallel. Results Circulating microparticles exhibited a considerable interdonor but not intergroup variation. Fresh frozen plasma units were enriched in microparticles compared to plasma in vivo. Duration of storage significantly affected platelet- and red cell-derived microparticles. Fresh frozen plasma prepared directly from whole blood contained more residual platelets and more platelet-derived microparticles compared to fresh frozen plasma prepared from platelet-rich plasma. Consequently, there was a statistically significant difference in total, platelet- and red cell-derived microparticles between the two preparation protocols over storage time in the freezer. Preservation of the thawed units for 24 h at 4 °C did not significantly alter microparticle accumulation. Microparticle accumulation and anti-oxidant capacity of fresh frozen plasma was positively or negatively correlated, respectively, with the level of circulating microparticles in individual donors. Discussion The preparation protocol and the duration of storage in the freezer, independently and in combination, influenced the accumulation of microparticles in fresh frozen plasma units. In contrast, storage of thawed units for 24 h at 4 °C had no significant effect on the concentration of microparticles. PMID:27136430

Microparticles variability in fresh frozen plasma: preparation protocol and storage time effects.

PubMed

Kriebardis, Anastasios G; Antonelou, Marianna H; Georgatzakou, Hara T; Tzounakas, Vassilis L; Stamoulis, Konstantinos E; Papassideri, Issidora S

2016-05-01

Extracellular vesicles or microparticles exhibiting procoagulant and thrombogenic activity may contribute to the haemostatic potential of fresh frozen plasma. Fresh frozen plasma was prepared from platelet-rich plasma at 20 °C (Group-1 donors) or directly from whole blood at 4 °C (Group-2 donors). Each unit was aseptically divided into three parts, stored frozen for specific periods of time, and analysed by flow cytometry for procoagulant activity immediately after thaw or following post-thaw storage for 24 h at 4 °C. Donors' haematologic, biochemical and life-style profiles as well as circulating microparticles were analysed in parallel. Circulating microparticles exhibited a considerable interdonor but not intergroup variation. Fresh frozen plasma units were enriched in microparticles compared to plasma in vivo. Duration of storage significantly affected platelet- and red cell-derived microparticles. Fresh frozen plasma prepared directly from whole blood contained more residual platelets and more platelet-derived microparticles compared to fresh frozen plasma prepared from platelet-rich plasma. Consequently, there was a statistically significant difference in total, platelet- and red cell-derived microparticles between the two preparation protocols over storage time in the freezer. Preservation of the thawed units for 24 h at 4 °C did not significantly alter microparticle accumulation. Microparticle accumulation and anti-oxidant capacity of fresh frozen plasma was positively or negatively correlated, respectively, with the level of circulating microparticles in individual donors. The preparation protocol and the duration of storage in the freezer, independently and in combination, influenced the accumulation of microparticles in fresh frozen plasma units. In contrast, storage of thawed units for 24 h at 4 °C had no significant effect on the concentration of microparticles.

Improvement of desolvation and resilience of alginate binders for Si-based anodes in a lithium ion battery by calcium-mediated cross-linking.

PubMed

Yoon, Jihee; Oh, Dongyeop X; Jo, Changshin; Lee, Jinwoo; Hwang, Dong Soo

2014-12-14

Si-based anodes in lithium ion batteries (LIBs) have exceptionally high theoretical capacity, but the use of a Si-based anode in LIBs is problematic because the charging-discharging process can fracture the Si particles. Alginate and its derivatives show promise as Si particle binders in the anode. We show that calcium-mediated "egg-box" electrostatic cross-linking of alginate improves toughness, resilience, electrolyte desolvation of the alginate binder as a Si-binder for LIBs. Consequently, the improved mechanical properties of the calcium alginate binder compared to the sodium alginate binder and other commercial binders extend the lifetime and increase the capacity of Si-based anodes in LIBs.

Formation of inhalable rifampicin-poly(L-lactide) microparticles by supercritical anti-solvent process.

PubMed

Patomchaiviwat, Vipaluk; Paeratakul, Ornlaksana; Kulvanich, Poj

2008-01-01

Formation of inhalable microparticles containing rifampicin and poly(L-lactide) (L-PLA) by using supercritical anti-solvent process (SAS) was investigated. The solutions of drug and polymer in methylene chloride were sprayed into supercritical carbon dioxide. The effect of polymer content and operating conditions, temperature, pressure, carbon dioxide molar fraction, and concentration of solution, on product characteristics were studied. The prepared microparticles were characterized with respect to their morphology, particle size and size distribution, drug content, drug loading efficiency, and drug release characteristic. Discrete, spherical microparticles were obtained at high polymer:drug ratios of 7:3, 8:2, and 9:1. The shape of L-PLA microparticles became more irregular and agglomerated with decreasing polymer content. Microparticles with polymer content higher than 60% exhibited volumetric mean diameter less than 5 microm, but percent drug loading efficiency was relatively low. Drug-loaded microparticles containing 70% and 80% L-PLA showed a sustainable drug release property without initial burst release. Operating temperature level influenced on mean size and size distribution of microparticles. The operating pressure and carbon dioxide molar fraction in the range investigated were unlikely to have an effect on microparticle formation. An increasing concentration of feed solution provided larger size microparticles. Rifampicin-loaded L-PLA microparticles could be produced by SAS in a size range suitable for dry powder inhaler formulation.

Microparticle analysis system and method

NASA Technical Reports Server (NTRS)

Morrison, Dennis R. (Inventor)

2007-01-01

A device for analyzing microparticles is provided which includes a chamber with an inlet and an outlet for respectively introducing and dispensing a flowing fluid comprising microparticles, a light source for providing light through the chamber and a photometer for measuring the intensity of light transmitted through individual microparticles. The device further includes an imaging system for acquiring images of the fluid. In some cases, the device may be configured to identify and determine a quantity of the microparticles within the fluid. Consequently, a method for identifying and tracking microparticles in motion is contemplated herein. The method involves flowing a fluid comprising microparticles in laminar motion through a chamber, transmitting light through the fluid, measuring the intensities of the light transmitted through the microparticles, imaging the fluid a plurality of times and comparing at least some of the intensities of light between different images of the fluid.

Decellularized extracellular matrix microparticles as a vehicle for cellular delivery in a model of anastomosis healing.

PubMed

Hoganson, David M; Owens, Gwen E; Meppelink, Amanda M; Bassett, Erik K; Bowley, Chris M; Hinkel, Cameron J; Finkelstein, Eric B; Goldman, Scott M; Vacanti, Joseph P

2016-07-01

Extracellular matrix (ECM) materials from animal and human sources have become important materials for soft tissue repair. Microparticles of ECM materials have increased surface area and exposed binding sites compared to sheet materials. Decellularized porcine peritoneum was mechanically dissociated into 200 µm microparticles, seeded with fibroblasts and cultured in a low gravity rotating bioreactor. The cells avidly attached and maintained excellent viability on the microparticles. When the seeded microparticles were placed in a collagen gel, the cells quickly migrated off the microparticles and through the gel. Cells from seeded microparticles migrated to and across an in vitro anastomosis model, increasing the tensile strength of the model. Cell seeded microparticles of ECM material have potential for paracrine and cellular delivery therapies when delivered in a gel carrier. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1728-1735, 2016. © 2016 Wiley Periodicals, Inc.

Lipid-induced toxicity stimulates hepatocytes to release angiogenic microparticles that require Vanin-1 for uptake by endothelial cells

PubMed Central

Povero, Davide; Eguchi, Akiko; Niesman, Ingrid R.; Andronikou, Nektaria; de Mollerat du Jeu, Xavier; Mulya, Anny; Berk, Michael; Lazic, Milos; Thapaliya, Samjana; Parola, Maurizio; Patel, Hemal H.; Feldstein, Ariel E.

2014-01-01

Angiogenesis is a key pathological feature of experimental and human steatohepatitis, a common chronic liver disease that is associated with obesity. We demonstrated that hepatocytes generated a type of membrane-bound vesicle, microparticles, in response to conditions that mimicked the lipid accumulation that occurs in the liver in some forms of steatohepatitis and that these microparticles promoted angiogenesis. When applied to an endothelial cell line, medium conditioned by murine hepatocytes or a human hepatocyte cell line exposed to saturated free fatty acids induced migration and tube formation, two processes required for angiogenesis. Medium from hepatocytes in which caspase 3 was inhibited or medium in which the microparticles were removed by ultracentrifugation lacked proangiogenic activity. Isolated hepatocyte-derived microparticles induced migration and tube formation of an endothelial cell line in vitro and angiogenesis in mice, processes that depended on internalization of microparticles. Microparticle internalization required the interaction of the ectoenzyme Vanin-1 (VNN1), an abundant surface protein on the microparticles, with lipid raft domains of endothelial cells. Large quantities of hepatocyte-derived microparticles were detected in the blood of mice with diet-induced steatohepatitis, and microparticle quantity correlated with disease severity. Genetic ablation of caspase 3 or RNA interference directed against VNN1 protected mice from steatohepatitis-induced pathological angiogenesis in the liver and resulted in a loss of the proangiogenic effects of microparticles. Our data identify hepatocyte-derived microparticles as critical signals that contribute to angiogenesis and liver damage in steatohepatitis and suggest a therapeutic target for this condition. PMID:24106341

Method for determining surface properties of microparticles

DOEpatents

Eisenthal, Kenneth B.

2000-01-01

Second harmonic generation (SHG), sum frequency generation (SFG) and difference frequency generation (DFG) can be used for surface analysis or characterization of microparticles having a non-metallic surface feature. The microparticles can be centrosymmetric or such that non-metallic molecules of interest are centrosymmetrically distributed inside and outside the microparticles but not at the surface of the microparticles where the asymmetry aligns the molecules. The signal is quadratic in incident laser intensity or proportional to the product of two incident laser intensities for SFG, it is sharply peaked at the second harmonic wavelength, quadratic in the density of molecules adsorbed onto the microparticle surface, and linear in microparticles density. In medical or pharmacological applications, molecules of interest may be of drugs or toxins, for example.

Effects of alginate on frozen-thawed boar spermatozoa quality, lipid peroxidation and antioxidant enzymes activities.

PubMed

Hu, Jinghua; Geng, Guoxia; Li, Qingwang; Sun, Xiuzhu; Cao, Hualin; Liu, Yawei

2014-06-30

Although alginate was reported to play an important role as free radical scavengers in vitro and could be used as sources of natural antioxidants, there was no study about the cryoprotective effects of alginate on boar spermatozoa freezing. The objective of this research was to evaluate the effects of different concentrations of alginate added to the freezing extenders on boar spermatozoa motility, plasma membrane integrity, acrosomal integrity, mitochondrial activities, lipid peroxidation and antioxidative enzymes activities (SOD and GSH-Px) after thawing. Alginate was added to the TCG extender to yield six different final concentrations: 0, 0.2, 0.4, 0.6, 0.8, and 1.0mg/mL. The semen extender supplemented with various doses of alginate increased (P<0.05) total motility. The spermatozoa plasma membrane integrity and mitochondrial activity were improved at four different concentrations: 0.4, 0.6, 0.8, 1.0mg/mL. The addition of alginate also provided significantly positive effect on post-thaw boar spermatozoa acrosomal integrity at concentrations of 0.6, 0.8, 1.0mg/mL, compared with that of the control (P<0.05). The freezing extenders with the presence of alginate led to higher SOD and GSH-Px activities and lower MDA levels, in comparison to the control (P<0.05). In summary, alginate exhibited a dose-related response on frozen-thawed boar spermatozoa motility, functional integrity and antioxidative capacity at appropriate concentrations. Therefore alginate could be employed as an effective cryoprotectant in boar spermatozoa cryopreservation. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy of chitosan and sodium alginate scaffolds for repair of spinal cord injury in rats

PubMed Central

Yao, Zi-ang; Chen, Feng-jia; Cui, Hong-li; Lin, Tong; Guo, Na; Wu, Hai-ge

2018-01-01

Spinal cord injury results in the loss of motor and sensory pathways and spontaneous regeneration of adult mammalian spinal cord neurons is limited. Chitosan and sodium alginate have good biocompatibility, biodegradability, and are suitable to assist the recovery of damaged tissues, such as skin, bone and nerve. Chitosan scaffolds, sodium alginate scaffolds and chitosan-sodium alginate scaffolds were separately transplanted into rats with spinal cord hemisection. Basso-Beattie-Bresnahan locomotor rating scale scores and electrophysiological results showed that chitosan scaffolds promoted recovery of locomotor capacity and nerve transduction of the experimental rats. Sixty days after surgery, chitosan scaffolds retained the original shape of the spinal cord. Compared with sodium alginate scaffolds- and chitosan-sodium alginate scaffolds-transplanted rats, more neurofilament-H-immunoreactive cells (regenerating nerve fibers) and less glial fibrillary acidic protein-immunoreactive cells (astrocytic scar tissue) were observed at the injury site of experimental rats in chitosan scaffold-transplanted rats. Due to the fast degradation rate of sodium alginate, sodium alginate scaffolds and composite material scaffolds did not have a supporting and bridging effect on the damaged tissue. Above all, compared with sodium alginate and composite material scaffolds, chitosan had better biocompatibility, could promote the regeneration of nerve fibers and prevent the formation of scar tissue, and as such, is more suitable to help the repair of spinal cord injury. PMID:29623937

Alginate-Iron Speciation and Its Effect on In Vitro Cellular Iron Metabolism

PubMed Central

Horniblow, Richard D.; Dowle, Miriam; Iqbal, Tariq H.; Latunde-Dada, Gladys O.; Palmer, Richard E.

2015-01-01

Alginates are a class of biopolymers with known iron binding properties which are routinely used in the fabrication of iron-oxide nanoparticles. In addition, alginates have been implicated in influencing human iron absorption. However, the synthesis of iron oxide nanoparticles employs non-physiological pH conditions and whether nanoparticle formation in vivo is responsible for influencing cellular iron metabolism is unclear. Thus the aims of this study were to determine how alginate and iron interact at gastric-comparable pH conditions and how this influences iron metabolism. Employing a range of spectroscopic techniques under physiological conditions alginate-iron complexation was confirmed and, in conjunction with aberration corrected scanning transmission electron microscopy, nanoparticles were observed. The results infer a nucleation-type model of iron binding whereby alginate is templating the condensation of iron-hydroxide complexes to form iron oxide centred nanoparticles. The interaction of alginate and iron at a cellular level was found to decrease cellular iron acquisition by 37% (p < 0.05) and in combination with confocal microscopy the alginate inhibits cellular iron transport through extracellular iron chelation with the resulting complexes not internalised. These results infer alginate as being useful in the chelation of excess iron, especially in the context of inflammatory bowel disease and colorectal cancer where excess unabsorbed luminal iron is thought to be a driver of disease. PMID:26378798

Alginate as a cell culture substrate for growth and differentiation of human retinal pigment epithelial cells.

PubMed

Heidari, Razeih; Soheili, Zahra-Soheila; Samiei, Shahram; Ahmadieh, Hamid; Davari, Maliheh; Nazemroaya, Fatemeh; Bagheri, Abouzar; Deezagi, Abdolkhalegh

2015-03-01

The purpose of this study was to evaluate retinal pigment epithelium (RPE) cells' behavior in alginate beads that establish 3D environment for cellular growth and mimic extracellular matrix versus the conventional 2D monolayer culture. RPE cells were encapsulated in alginate beads by dripping alginate cell suspension into CaCl2 solution. Beads were suspended in three different media including Dulbecco's modified Eagle's medium (DMEM)/F12 alone, DMEM/F12 supplemented with 10 % fetal bovine serum (FBS), and DMEM/F12 supplemented with 30 % human amniotic fluid (HAF). RPE cells were cultivated on polystyrene under the same conditions as controls. Cell phenotype, cell proliferation, cell death, and MTT assay, immunocytochemistry, and real-time RT-PCR were performed to evaluate the effect of alginate on RPE cells characteristics and integrity. RPE cells can survive and proliferate in alginate matrixes. Immunocytochemistry analysis exhibited Nestin, RPE65, and cytokeratin expressions in a reasonable number of cultured cells in alginate beads. Real-time PCR data demonstrated high levels of Nestin, CHX10, RPE65, and tyrosinase gene expressions in RPE cells immobilized in alginate when compared to 2D monolayer culture systems. The results suggest that alginate can be used as a reliable scaffold for maintenance of RPE cells' integrity and in vitro propagation of human retinal progenitor cells for cell replacement therapies in retinal diseases.

Review: efficacy of alginate supplementation in relation to appetite regulation and metabolic risk factors: evidence from animal and human studies.

PubMed

Georg Jensen, M; Pedersen, C; Kristensen, M; Frost, G; Astrup, A

2013-02-01

This review provides a critical update on human and animal studies investigating the effect of alginate supplementation on appetite regulation, glycaemic and insulinemic responses, and lipid metabolism with discussion of the evidence on potential mechanisms, efficacy and tolerability. Dependent on vehicle applied for alginate supplementation, the majority of animal and human studies suggest that alginate consumption does suppress satiety and to some extent energy intake. Only one long-term intervention trial found effects on weight loss. In addition, alginates seem to exhibit beneficial influence on postprandial glucose absorption and insulin response in animals and humans. However, alginate supplementation was only found to have cholesterol-lowering properties in animals. Several mechanisms have been suggested for the positive effect observed, which involve delayed gastric emptying, increased viscosity of digesta and slowed nutrient absorption in the small intestine upon alginate gel formation. Despite reasonable efficacy and tolerability from the acute or short-term studies, we still realize there is a critical need for development of optimal alginate types and vehicles as well as studies on further long-term investigation on alginate supplementation in humans before inferring that it could be useful in the management of obesity and the metabolic syndrome. © 2012 The Authors. obesity reviews © 2012 International Association for the Study of Obesity.

The acetylation degree of alginates in Azotobacter vinelandii ATCC9046 is determined by dissolved oxygen and specific growth rate: studies in glucose-limited chemostat cultivations.

PubMed

Castillo, Tania; Galindo, Enrique; Peña, Carlos F

2013-07-01

Alginates are polysaccharides that may be used as viscosifiers and gel or film-forming agents with a great diversity of applications. The alginates produced by bacteria such as Azotobacter vinelandii are acetylated. The presence of acetyl groups in this type of alginate increases its solubility, viscosity, and swelling capability. The aim of this study was to evaluate, in glucose-limited chemostat cultivations of A. vinelandii ATCC9046, the influence of dissolved oxygen tension (DO) and specific growth rate (μ) on the degree of acetylation of alginates produced by this bacterium. In glucose-limited chemostat cultivations, the degree of alginate acetylation was evaluated under two conditions of DO (1 and 9 %) and for a range of specific growth rates (0.02-0.15 h⁻¹). In addition, the alginate yields and PHB production were evaluated. High DO in the culture resulted in a high degree of alginate acetylation, reaching a maximum acetylation degree of 6.88 % at 9 % DO. In contrast, the increment of μ had a negative effect on the production and acetylation of the polymer. It was found that at high DO (9 %) and low μ, there was a reduction of the respiration rate, and the PHB accumulation was negligible, suggesting that the flux of acetyl-CoA (the acetyl donor) was diverted to alginate acetylation.

Jellyfish collagen and alginate: Combined marine materials for superior chondrogenesis of hMSC.

PubMed

Pustlauk, W; Paul, B; Gelinsky, M; Bernhardt, A

2016-07-01

Marine, hybrid constructs of porous scaffolds from fibrillized jellyfish collagen and alginate hydrogel are mimicking both of the main tissue components of cartilage, thus being a promising approach for chondrogenic differentiation of human mesenchymal stem cells (hMSC). Investigating their potential for articular cartilage repair, the present study examined scaffolds being either infiltrated with an alginate-cell-suspension (ACS) or seeded with hMSC and embedded in alginate after cell adhesion (EAS). Hybrid constructs with 2×10(5) and 4.5×10(5)hMSC/scaffold were compared to hMSC encapsulated in pure alginate discs, both chondrogenically stimulated for 21days. Typical round, chondrocyte-like morphology was observed in pure alginate gels and ACS scaffolds, while cells in EAS were elongated and tightly attached to the collagen pores. Col 2 gene expression was comparable in all scaffold types examined. However, the Col 2/Col 1 ratio was higher for pure alginate discs and ACS scaffolds compared to EAS. In contrast, cells in EAS scaffolds displayed higher gene expression of Sox 9, Col 11 and ACAN compared to ACS and pure alginate. Secretion of sulfated glycosaminoglycans (sGAG) was comparable for ACS and EAS scaffolds. In conclusion hybrid constructs of jellyfish collagen and alginate support hMSC chondrogenic differentiation and provide more stable and constructs compared to pure hydrogels. Copyright © 2016 Elsevier B.V. All rights reserved.

A Facile Bottom-Up Approach to Construct Hybrid Flexible Cathode Scaffold for High-Performance Lithium-Sulfur Batteries.

PubMed

Ghosh, Arnab; Manjunatha, Revanasiddappa; Kumar, Rajat; Mitra, Sagar

2016-12-14

Lithium-sulfur batteries mostly suffer from the low utilization of sulfur, poor cycle life, and low rate performances. The prime factors that affect the performance are enormous volume change of the electrode, soluble intermediate product formation, poor electronic and ionic conductivity of S, and end discharge products (i.e., Li 2 S 2 and Li 2 S). The attractive way to mitigate these challenges underlying in the fabrication of a sulfur nanocomposite electrode consisting of different nanoparticles with distinct properties of lithium storage capability, mechanical reinforcement, and ionic as well as electronic conductivity leading to a mechanically robust and mixed conductive (ionic and electronic conductive) sulfur electrode. Herein, we report a novel bottom-up approach to synthesize a unique freestanding, flexible cathode scaffold made of porous reduced graphene oxide, nanosized sulfur, and Mn 3 O 4 nanoparticles, and all are three-dimensionally interconnected to each other by hybrid polyaniline/sodium alginate (PANI-SA) matrix to serve individual purposes. A capacity of 1098 mAh g -1 is achieved against lithium after 200 cycles at a current rate of 2 A g -1 with 97.6% of initial capacity at a same current rate, suggesting the extreme stability and cycling performance of such electrode. Interestingly, with the higher current density of 5 A g -1 , the composite electrode exhibited an initial capacity of 1015 mA h g -1 and retained 71% of the original capacity after 500 cycles. The in situ Raman study confirms the polysulfide absorption capability of Mn 3 O 4 . This work provides a new strategy to design a mechanically robust, mixed conductive nanocomposite electrode for high-performance lithium-sulfur batteries and a strategy that can be used to develop flexible large power storage devices.

External and internal gelation of pectin solutions: microscopic dynamics versus macroscopic rheology

NASA Astrophysics Data System (ADS)

Secchi, E.; Munarin, F.; Alaimo, M. D.; Bosisio, S.; Buzzaccaro, S.; Ciccarella, G.; Vergaro, V.; Petrini, P.; Piazza, R.

2014-11-01

Pectin is a natural biopolymer that forms, in the presence of divalent cations, ionic-bound gels typifying a large class of biological gels stabilized by non-covalent cross-links. We investigate and compare the kinetics of formation and aging of pectin gels obtained either through external gelation via perfusion of free Ca2+ ions, or by internal gelation due to the supply of the same ions from the dissolution of CaCO3 nanoparticles. The microscopic dynamics obtained with photon correlation imaging, a novel optical technique that allows obtaining the microscopic dynamics of the sample while retaining the spatial resolution of imaging techniques, is contrasted with macroscopic rheological measurements at constant strain. Pectin gelation is found to display peculiar two-stage kinetics, highlighted by non-monotonic growth in time of both microscopic correlations and gel mechanical strength. These results are compared to those found for alginate, another biopolymer extensively used in food formulation.

High surface area mesoporous activated carbon-alginate beads for efficient removal of methylene blue.

PubMed

Nasrullah, Asma; Bhat, A H; Naeem, Abdul; Isa, Mohamed Hasnain; Danish, Mohammed

2018-02-01

High surface area mesoporous activated carbon-alginate (AC-alginate) beads were successfully synthesized by entrapping activated carbon powder derived from Mangosteen fruit peel into calcium-alginate beads for methylene blue (MB) removal from aqueous solution. The structure and surface characteristics of AC-alginate beads were analyzed using Fourier transform infra-red (FTIR) spectroscopy, scanning electron microscopy (SEM) and surface area analysis (S BET ), while thermal properties were tested using thermogravimetric analysis (TGA). The effect of AC-alginate dose, pH of solution, contact time, initial concentration of MB solution and temperature on MB removal was elucidated. The results showed that the maximum adsorption capacity of 230mg/g was achieved for 100mg/L of MB solution at pH 9.5 and temperature 25°C. Furthermore, the adsorption of MB on AC-alginate beads followed well pseudo-second order equation and equilibrium adsorption data were better fitted by the Freundlich isotherm model. The findings reveal the feasibility of AC-alginate beads composite to be used as a potential and low cost adsorbent for removal of cationic dyes. Copyright © 2017 Elsevier B.V. All rights reserved.

Encapsulating Non-Human Primate Multipotent Stromal Cells in Alginate via High Voltage for Cell-Based Therapies and Cryopreservation

PubMed Central

Gryshkov, Oleksandr; Pogozhykh, Denys; Hofmann, Nicola; Pogozhykh, Olena; Mueller, Thomas; Glasmacher, Birgit

2014-01-01

Alginate cell-based therapy requires further development focused on clinical application. To assess engraftment, risk of mutations and therapeutic benefit studies should be performed in an appropriate non-human primate model, such as the common marmoset (Callithrix jacchus). In this work we encapsulated amnion derived multipotent stromal cells (MSCs) from Callithrix jacchus in defined size alginate beads using a high voltage technique. Our results indicate that i) alginate-cell mixing procedure and cell concentration do not affect the diameter of alginate beads, ii) encapsulation of high cell numbers (up to 10×106 cells/ml) can be performed in alginate beads utilizing high voltage and iii) high voltage (15–30 kV) does not alter the viability, proliferation and differentiation capacity of MSCs post-encapsulation compared with alginate encapsulated cells produced by the traditional air-flow method. The consistent results were obtained over the period of 7 days of encapsulated MSCs culture and after cryopreservation utilizing a slow cooling procedure (1 K/min). The results of this work show that high voltage encapsulation can further be maximized to develop cell-based therapies with alginate beads in a non-human primate model towards human application. PMID:25259731

Alginate as immobilization matrix and stabilizing agent in a two-phase liquid system: application in lipase-catalysed reactions.

PubMed

Hertzberg, S; Kvittingen, L; Anthonsen, T; Skjåk-Braek, G

1992-01-01

Alginate was evaluated as an immobilization matrix for enzyme-catalyzed reactions in organic solvents. In contrast to most hydrogels, calcium alginate was found to be stable in a range of organic solvents and to retain the enzyme inside the gel matrix. In hydrophobic solvents, the alginate gel (greater than 95% water) thus provided a stable, two-phase liquid system. The lipase from Candida cylindracea, after immobilization in alginate beads, catalysed esterification and transesterification in n-hexane under both batch and continuous-flow conditions. The operational stability of the lipase was markedly enhanced by alginate entrapment. In the esterification of butanoic acid with n-butanol, better results were obtained in the typical hydrophilic calcium alginate beads than in less hydrophilic matrices. The effects of substrate concentration, matrix area, and polarity of the substrate alcohols and of the organic solvent on the esterification activity were examined. The transesterification of octyl 2-bromopropanoate with ethanol was less efficient than that of ethyl 2-bromopropanoate with octanol. By using the hydrophilic alginate gel as an immobilization matrix in combination with a mobile hydrophobic phase, a two-phase liquid system was achieved with definite advantages for a continuous, enzyme-catalysed process.

Impact of higher alginate expression on deposition of Pseudomonas aeruginosa in radial stagnation point flow and reverse osmosis systems.

PubMed

Herzberg, Moshe; Rezene, Tesfalem Zere; Ziemba, Christopher; Gillor, Osnat; Mathee, Kalai

2009-10-01

Extracellular polymeric substances (EPS) have major impact on biofouling of reverse osmosis (RO) membranes. On one hand, EPS can reduce membrane permeability and on the other, EPS production by the primary colonizers may influence their deposition and attachment rate and subsequently affect the biofouling propensity of the membrane. The role of bacterial exopolysaccharides in bacterial deposition followed by the biofouling potential of an RO membrane was evaluated using an alginate overproducing (mucoid) Pseudomonas aeruginosa. The mucoid P. aeruginosa PAOmucA22 was compared with its isogenic nonmucoid prototypic parent PAO1 microscopically in a radial stagnation point flow (RSPF) system for their bacterial deposition characteristics. Then, biofouling potential of PAO1 and PAOmucA22 was determined in a crossflow rectangular plate-and-frame membrane cell, in which the strains were cultivated on a thin-film composite, polyamide, flat RO membrane coupon (LFC-1) under laminar flow conditions. In the RSPF system, the observed deposition rate of the mucoid strain was between 5- and 10-fold lower than of the wild type using either synthetic wastewater medium (with ionic strength of 14.7 mM and pH 7.4) or 15 mM KCl solution (pH of 6.2). The slower deposition rate of the mucoid strain is explained by 5- to 25-fold increased hydrophilicity of the mucoid strain as compared to the isogenic wild type, PAO1. Corroborating with these results, a significant delay in the onset of biofouling of the RO membrane was observed when the mucoid strain was used as the membrane colonizer, in which the observed time for the induced permeate flux decline was delayed (ca. 2-fold). In conclusion, the lower initial cell attachment of the mucoid strain decelerated biofouling of the RO membrane. Bacterial deposition and attachment is a critical step in biofilm formation and governed by intimate interactions between outer membrane proteins of the bacteria and the surface. Shielding these interactions by a hydrated and hydrophilic alginate capsule is shown to dramatically lessen the biofouling potential of the membrane colonizers.

Antimicrobial cerium ion-chitosan crosslinked alginate biopolymer films: A novel and potential wound dressing.

PubMed

Kaygusuz, Hakan; Torlak, Emrah; Akın-Evingür, Gülşen; Özen, İlhan; von Klitzing, Regine; Erim, F Bedia

2017-12-01

Wound dressings require good antiseptic properties, mechanical strength and, more trustably, natural material ingredients. Antimicrobial properties of cerium ions and chitosan are known and alginate based wound dressings are commercially available. In this study, the advantages of these materials were combined and alginate films were crosslinked with cerium(III) solution and chitosan added cerium(III) solution. Films were characterized by Fourier transform infrared spectroscopy (FTIR), light transmittance, scanning electron microscopy (SEM), swelling experiments, water vapor transmittance tests, and mechanical stretching tests. The antibacterial and physical properties of the films were compared with those of conventional calcium alginate films. Both cerium ion crosslinked and cerium ion-chitosan crosslinked alginate films gained antibacterial activity against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. Cerium alginate-chitosan films showed high resistance to being deformed elastically. Results show that cerium alginate-chitosan films can be flexible, ultraviolet-protecting, and antibacterial wound dressings. Copyright © 2017 Elsevier B.V. All rights reserved.

Copper-releasing, boron-containing bioactive glass-based scaffolds coated with alginate for bone tissue engineering.

PubMed

Erol, M M; Mouriňo, V; Newby, P; Chatzistavrou, X; Roether, J A; Hupa, L; Boccaccini, Aldo R

2012-02-01

The aim of this study was to synthesize and characterize new boron-containing bioactive glass-based scaffolds coated with alginate cross-linked with copper ions. A recently developed bioactive glass powder with nominal composition (wt.%) 65 SiO2, 15 CaO, 18.4 Na2O, 0.1 MgO and 1.5 B2O3 was fabricated as porous scaffolds by the foam replica method. Scaffolds were alginate coated by dipping them in alginate solution. Scanning electron microscopy investigations indicated that the alginate effectively attached on the surface of the three-dimensional scaffolds leading to a homogeneous coating. It was confirmed that the scaffold structure remained amorphous after the sintering process and that the alginate coating improved the scaffold bioactivity and mechanical properties. Copper release studies showed that the alginate-coated scaffolds allowed controlled release of copper ions. The novel copper-releasing composite scaffolds represent promising candidates for bone regeneration. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Alginate Microcapsules Incorporating Hyaluronic Acid Recreate Closer in Vivo Environment for Mesenchymal Stem Cells.

PubMed

Cañibano-Hernández, Alberto; Saenz Del Burgo, Laura; Espona-Noguera, Albert; Orive, Gorka; Hernández, Rosa M; Ciriza, Jesús; Pedraz, Jose Luis

2017-07-03

The potential clinical application of alginate cell microencapsulation has advanced enormously during the past decade. However, the 3D environment created by alginate beads does not mimic the natural extracellular matrix surrounding cells in vivo, responsible of cell survival and functionality. As one of the most frequent macromolecules present in the extracellular matrix is hyaluronic acid, we have formed hybrid beads with alginate and hyaluronic acid recreating a closer in vivo cell environment. Our results show that 1% alginate-0.25% hyaluronic acid microcapsules retain 1.5% alginate physicochemical properties. Moreover, mesenchymal stem cells encapsulated in these hybrid beads show enhanced viability therapeutic protein release and mesenchymal stem cells' potential to differentiate into chondrogenic lineage. Although future studies with additional proteins need to be done in order to approach even more the extracellular matrix features, we have shown that hyaluronic acid protects alginate encapsulated mesenchymal stem cells by providing a niche-like environment and remaining them competent as a sustainable drug delivery system.

Milled non-mulberry silk fibroin microparticles as biomaterial for biomedical applications.

PubMed

Bhardwaj, Nandana; Rajkhowa, Rangam; Wang, Xungai; Devi, Dipali

2015-11-01

Silk fibroin has been widely employed in various forms as biomaterials for biomedical applications due to its superb biocompatibility and tunable degradation and mechanical properties. Herein, silk fibroin microparticles of non-mulberry silkworm species (Antheraea assamensis, Antheraea mylitta and Philosamia ricini) were fabricated via a top-down approach using a combination of wet-milling and spray drying techniques. Microparticles of mulberry silkworm (Bombyx mori) were also utilized for comparative studies. The fabricated microparticles were physico-chemically characterized for size, stability, morphology, chemical composition and thermal properties. The silk fibroin microparticles of all species were porous (∼5μm in size) and showed nearly spherical morphology with rough surface as revealed from dynamic light scattering and microscopic studies. Non-mulberry silk microparticles maintained the typical silk-II structure with β-sheet secondary conformation with higher thermal stability. Additionally, non-mulberry silk fibroin microparticles supported enhanced cell adhesion, spreading and viability of mouse fibroblasts than mulberry silk fibroin microparticles (p<0.001) as evidenced from fluorescence microscopy and cytotoxicity studies. Furthermore, in vitro drug release from the microparticles showed a significantly sustained release over 3 weeks. Taken together, this study demonstrates promising attributes of non-mulberry silk fibroin microparticles as a potential drug delivery vehicle/micro carrier for diverse biomedical applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Plasma-derived microparticles in polycythaemia vera.

PubMed

Ahadon, M; Abdul Aziz, S; Wong, C L; Leong, C F

2018-04-01

Microparticles are membrane bound vesicles, measuring less than 1.0 um, which are released during cellular activation or during apoptosis. Studies have shown that these circulating microparticles play a role in coagulation, cell signaling and cellular interactions. Increased levels of circulating microparticles have been observed in a number of conditions where there is vascular dysfunction, thrombosis and inflammation. The objective of this study was to determine the various plasma-derived microparticles in patients with polycythaemia vera (PV) in Universiti Kebangsaan Malaysia Medical Centre and to compare them with normal control. A total of 15 patients with PV and 15 healthy volunteers were included in this cross-sectional descriptive study. Plasma samples from both patients and healthy volunteers were prepared and further processed for isolation of microparticles. Flow cytometry analyses were then carried out in all samples to determine the cellular origin of the microparticles. Full blood count parameters for both groups were also collected. Data collected were analyzed using SPSS version 12.0. Patients with PV had a significantly higher percentage of platelet derived microparticles compared to healthy controls (P <0.05). The control group had a higher level of endothelial derived microparticles but the differences were not statistically significant (P > 0.05). The median percentage of positive events for platelet derived microparticles was higher in patients with PV compared to normal healthy controls.

Mitotic trafficking of silicon microparticles†

PubMed Central

Serda, Rita E.; Ferrati, Silvia; Godin, Biana; Tasciotti, Ennio; Liu, XueWu

2010-01-01

Multistage carriers were recently introduced by our laboratory, with the concurrent objectives of co-localized delivery of multiple therapeutic agents, the “theranostic” integration of bioactive moieties with imaging contrast, and the selective, potentially personalized bypassing of the multiplicity of biological barriers that adversely impact biodistribution of vascularly injected particulates. Mesoporous (“nanoporous”) silicon microparticles were selected as primary carriers in multi-stage devices, with targets including vascular endothelia at pathological lesions. The objective of this study was to evaluate biocompatibility of mesoporous silicon microparticles with endothelial cells using in vitro assays with an emphasis on microparticle compatibility with mitotic events. We observed that vascular endothelial cells, following internalization of silicon microparticles, maintain cellular integrity, as demonstrated by cellular morphology, viability and intact mitotic trafficking of vesicles bearing silicon microparticles. The presence of gold or iron oxide nanoparticles within the porous matrix did not alter the cellular uptake of particles or the viability of endothelial cells subsequent to engulfment of microparticles. Endothelial cells maintained basal levels of IL-6 and IL-8 release in the presence of silicon microparticles. This is the first study that demonstrates polarized, ordered partitioning of endosomes based on tracking microparticles. The finding that mitotic sorting of endosomes is unencumbered by the presence of nanoporous silicon microparticles advocates the use of silicon microparticles for biomedical applications. PMID:20644846

Cryopreservation alters the membrane and cytoskeletal protein profile of platelet microparticles.

PubMed

Raynel, Sarah; Padula, Matthew P; Marks, Denese C; Johnson, Lacey

2015-10-01

Cryopreservation of platelets (PLTs) in dimethyl sulfoxide (DMSO) and storage at -80 °C extends the PLT shelf life to at least 2 years, allowing greater accessibility in military and rural environments. While cryopreserved PLTs have been extensively characterized, the microparticles formed as a result of cryopreservation are yet to be fully described. Apheresis PLTs were cryopreserved at -80 °C with 5% DMSO and sampled before freezing and after thawing. Microparticle number, size, surface receptor phenotype, and function were assessed by microscopy, flow cytometry, dynamic light scattering, and thrombin-generating capacity. Proteomic changes were examined using two-dimensional gel electrophoresis and Western blotting. PLT cryopreservation resulted in a 15-fold increase in the number of microparticles compared to fresh PLTs. The surface receptor phenotype of these microparticles differed to microparticles from fresh PLTs, with more microparticles expressing glycoprotein (GP)IV, GPIIb, and the GPIb-V-IX complex. Cryopreservation drastically altered the abundance of many cytoskeletal proteins in the PLT microparticles, including actin, filamin, gelsolin, and tropomyosin. Despite these changes, PLT microparticles were functional and contributed to phosphatidylserine- and tissue factor- induced thrombin generation. This study demonstrates that PLT microparticles formed by cryopreservation are phenotypically distinct from those present before freezing. These differences may be associated with the procoagulant properties of cryopreserved PLTs. © 2015 AABB.

Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

PubMed

Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

2014-10-15

Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

Montmorillonite-Alginate Composites as a Drug delivery System: Intercalation and In vitro Release of Diclofenac sodium

PubMed Central

Kevadiya, B. D.; Patel, H. A.; Joshi, G. V.; Abdi, S. H. R.; Bajaj, H. C.

2010-01-01

Diclofenac sodium and alginate was intercalated into montmorillonite to form uniform sized beads by gelation method. The structure and surface morphology of the synthesized composite beads were characterized by powdered X-ray diffraction, Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning electron microscopy. Diclofenac release kinetics of the composite in simulated intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in vitro release of diclofenac from diclofenac-montmorillonite-alginate composites bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation efficiency in the montmorillonite-alginate composites bead increases with an increase in the montmorillonite content. The control release of diclofenac from diclofenac-montmorillonite-alginate composites beads was observed to be better as compared to diclofenac-alginate beads. PMID:21969745

Monitoring structural features, biocompatibility and biological efficacy of gamma-irradiated methotrexate-loaded spray-dried microparticles.

PubMed

de Oliveira, Alice R; Mesquita, Philippe C; Machado, Paula R L; Farias, Kleber J S; de Almeida, Yêda M B; Fernandes-Pedrosa, Matheus F; Cornélio, Alianda M; do Egito, Eryvaldo Sócrates T; da Silva-Júnior, Arnóbio A

2017-11-01

In this study, biodegradable and biocompatible gamma irradiated poly-(dl-lactide-co-glycolide) (PLGA) spray-dried microparticles were prepared aiming to improve the efficacy of methotrexate (MTX). The experimental design included three formulations of microparticles containing distinct drug amount (9%, 18%, and 27% w/w) and three distinct gamma irradiation dose (15kGy, 25kGy, and 30kGy). The physicochemical and drug release properties of the microparticles supported their biocompatibility and biological efficacy studies in different cell lines. The irradiation induced slight changes in the spherical shape of the microparticles and the formation of free radicals was dependent on the drug loading. However, the amorphous character, particle size, drug loading, and drug release rate of the microparticles were preserved. The drug release data from all microparticles formulation were evaluated by using four drug kinetic models and by comparison of their similarity factor (f 2 ). The gamma irradiation did not induce changes in the biocompatibility of PLGA microparticles and in the biological activity of the MTX-loaded microparticles. Finally, the spray-dried MTX-loaded PLGA microparticles enhanced the efficacy of the drug in the human cervical cancer cells (SiHa cell line). This study demonstrated the feasibility of the gamma irradiated spray dried PLGA microparticles for prolonged release of MTX, supporting a promising antitumor-drug delivery system for parenteral (subcutaneous) or pulmonary use. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterisation of the Poly-(Vinylpyrrolidone)-Poly-(Vinylacetate-Co-Crotonic Acid) (PVP:PVAc-CA) Interpolymer Complex Matrix Microparticles Encapsulating a Bifidobacterium lactis Bb12 Probiotic Strain.

PubMed

Mamvura, C I; Moolman, F S; Kalombo, L; Hall, A N; Thantsha, M S

2011-06-01

The method of producing poly-(vinylpyrrolidone)-poly-(vinylacetate-co-crotonic acid) (PVP:PVAc-CA) interpolymer complex matrix microparticles in supercritical carbon dioxide (scCO2), encapsulating bacteria, has recently been developed. This study was aimed at probing the external and internal structure of these microparticles, which can be used in food. The encapsulation efficiency and distribution of encapsulated Bifidobacterium lactis Bb12 within these microparticles were also investigated. Scanning electron microscopy (SEM) revealed irregular, mostly small, smooth microparticles with no visible bacterial cells on the surface. However, some of the microparticles appeared to have porous surfaces. The results of a Microtrac S3500 particle size analyzer showed that the PVP:PVAc-CA interpolymer complex matrix microparticles encapsulating B. lactis Bb12 had an average particle size of 166.1 μm (<350 μm designated standard size for microparticles). The D 10, D 50 and D 90 values for these microparticles were 48.16, 166.06 and 382.55 μm, respectively. Both SEM and confocal laser scanning microscopy showed a high density of bacterial cells within the microparticles. An average encapsulation efficiency of 96% was achieved. Consequently, the microparticles have the potential to be evenly distributed in foods, deliver adequate amounts of probiotics and produce minimal adverse effects on the texture and mouth feel of the foods into which they are incorporated.

Circulating Mesenchymal Stem Cells Microparticles in Patients with Cerebrovascular Disease

PubMed Central

Cho, Yeon Hee; Kang, Ho Young; Hyung, Na Kyum; Kim, Donghee; Lee, Ji Hyun; Nam, Ji Yoon; Bang, Oh Young

2012-01-01

Preclinical and clinical studies have shown that the application of CD105+ mesenchymal stem cells (MSCs) is feasible and may lead to recovery after stroke. In addition, circulating microparticles are reportedly functional in various disease conditions. We tested the levels of circulating CD105+ microparticles in patients with acute ischemic stroke. The expression of CD105 (a surface marker of MSCs) and CXCR4 (a CXC chemokine receptor for MSC homing) on circulating microparticles was evaluated by flow cytometry of samples from 111 patients and 50 healthy subjects. The percentage of apoptotic CD105 microparticles was determined based on annexin V (AV) expression. The relationship between serum levels of CD105+/AV− microparticles, stromal cells derived factor-1α (SDF-1α), and the extensiveness of cerebral infarcts was also evaluated. CD105+/AV− microparticles were higher in stroke patients than control subjects. Correlation analysis showed that the levels of CD105+/AV− microparticles increased as the baseline stroke severity increased. Multivariate testing showed that the initial severity of stroke was independently associated with circulating CD105+/AV− microparticles (OR, 1.103 for 1 point increase in the NIHSS score on admission; 95% CI, 1.032–1.178) after adjusting for other variables. The levels of CD105+/CXCR4+/AV− microparticles were also increased in patients with severe disability (r = 0.192, p = 0.046 for NIHSS score on admission), but were decreased with time after stroke onset (r = −0.204, p = 0.036). Risk factor profiles were not associated with the levels of circulating microparticles or SDF-1α. In conclusion, our data showed that stroke triggers the mobilization of MSC-derived microparticles, especially in patients with extensive ischemic stroke. PMID:22615882

Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer.

PubMed

Grill, Alex E; Shahani, Komal; Koniar, Brenda; Panyam, Jayanth

2018-04-01

Curcumin has shown promising inhibitory activity against HER-2-positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3 weeks compared to that in control mice that received empty microparticles. At 12 weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κΒ. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention.

Roughness-controlled self-assembly of mannitol/LB agar microparticles by polymorphic transformation for pulmonary drug delivery.

PubMed

Zhang, Fengying; Ngoc, Nguyen Thi Quynh; Tay, Bao Hui; Mendyk, Aleksander; Shao, Yu-Hsuan; Lau, Raymond

2015-01-05

Novel roughness-controlled mannitol/LB Agar microparticles were synthesized by polymorphic transformation and self-assembly method using hexane as the polymorphic transformation reagent and spray-dried mannitol/LB Agar microparticles as the starting material. As-prepared microparticles were characterized by Fourier transform infrared spectra (FTIR), X-ray diffraction spectra (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and Andersen Cascade Impactor (ACI). The XRD and DSC results indicate that after immersing spray-dried mannitol/LB Agar microparticles in hexane, β-mannitol was completely transformed to α-mannitol in 1 h, and all the δ-mannitol was transformed to α form after 14 days. SEM shows that during the transformation the nanobelts on the spray-dried mannitol/LB Agar microparticles become more dispersed and the contour of the individual nanobelts becomes more noticeable. Afterward, the nanobelts self-assemble to nanorods and result in rod-covered mannitol/LB Agar microparticles. FTIR indicates new hydrogen bonds were formed among mannitol, LB Agar, and hexane. SEM images coupled with image analysis software reveal that different surface morphology of the microparticles have different drug adhesion mechanisms. Comparison of ACI results and image analysis of SEM images shows that an increase in the particle surface roughness can increase the fine particle fractions (FPFs) using the rod-covered mannitol microparticles as drug carriers. Transformed microparticles show higher FPFs than commercially available lactose carriers. An FPF of 28.6 ± 2.4% was achieved by microparticles transformed from spray-dried microparticles using 2% mannitol(w/v)/LB Agar as feed solution. It is comparable to the highest FPF reported in the literature using lactose and spray-dried mannitol as carriers.

A conformational landscape for alginate secretion across the outer membrane of Pseudomonas aeruginosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Jingquan; Rouse, Sarah L.; Li, Dianfan

2014-08-01

Crystal structures of the β-barrel porin AlgE reveal a mechanism whereby alginate is exported from P. aeruginosa for biofilm formation. The exopolysaccharide alginate is an important component of biofilms produced by Pseudomonas aeruginosa, a major pathogen that contributes to the demise of cystic fibrosis patients. Alginate exits the cell via the outer membrane porin AlgE. X-ray structures of several AlgE crystal forms are reported here. Whilst all share a common β-barrel constitution, they differ in the degree to which loops L2 and T8 are ordered. L2 and T8 have been identified as an extracellular gate (E-gate) and a periplasmic gatemore » (P-gate), respectively, that reside on either side of an alginate-selectivity pore located midway through AlgE. Passage of alginate across the membrane is proposed to be regulated by the sequential opening and closing of the two gates. In one crystal form, the selectivity pore contains a bound citrate. Because citrate mimics the uronate monomers of alginate, its location is taken to highlight a route through AlgE taken by alginate as it crosses the pore. Docking and molecular-dynamics simulations support and extend the proposed transport mechanism. Specifically, the P-gate and E-gate are flexible and move between open and closed states. Citrate can leave the selectivity pore bidirectionally. Alginate docks stably in a linear conformation through the open pore. To translate across the pore, a force is required that presumably is provided by the alginate-synthesis machinery. Accessing the open pore is facilitated by complex formation between AlgE and the periplasmic protein AlgK. Alginate can thread through a continuous pore in the complex, suggesting that AlgK pre-orients newly synthesized exopolysaccharide for delivery to AlgE.« less

Evaluation of outgassing, tear strength, and detail reproduction in alginate substitute materials.

PubMed

Baxter, R T; Lawson, N C; Cakir, D; Beck, P; Ramp, L C; Burgess, J O

2012-01-01

To compare three alginate substitute materials to an alginate impression material for cast surface porosity (outgassing), tear strength, and detail reproduction. Detail reproduction tests were performed following American National Standards Institute/American Dental Association (ANSI/ADA) Specification No. 19. To measure tear strength, 12 samples of each material were made using a split mold, placed in a water bath until testing, and loaded in tension until failure at a rate of 500 mm/min using a universal testing machine. For cast surface porosity testing, five impressions of a Teflon mold with each material were placed in a water bath (37.8°C) for the in-mouth setting time and poured with vacuum-mixed Silky Rock die stone at 5, 10, 30, and 60 minutes from the start of mixing. The gypsum samples were analyzed with a digital microscope for surface porosity indicative of hydrogen gas release by comparing the surface obtained at each interval with four casts representing no, little, some, and significant porosity. Data analysis was performed using parametric and Kruskal-Wallis analysis of variance (ANOVA), Tukey/Kramer post-hoc tests (α=0.05), and individual Mann-Whitney U tests (α=0.0167). All alginate substitute materials passed the detail reproduction test. Tear strength of the alginate substitute materials was significantly better than alginate and formed three statistically different groups: AlgiNot had the lowest tear strength, Algin-X Ultra had the highest tear strength, and Position Penta Quick had intermediate tear strength. Significant variation in outgassing existed between materials and pouring times (p<0.05). All alginate substitute materials exhibited the least outgassing and cast porosity 60 minutes after mixing. Detail reproduction and tear strength of alginate substitute materials were superior to traditional alginate. The outgassing effect was minimal for most materials tested. Alginate substitute materials are superior replacements for irreversible hydrocolloid.

An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease.

PubMed

Rohof, Wout O; Bennink, Roel J; Smout, Andre J P M; Thomas, Edward; Boeckxstaens, Guy E

2013-12-01

Alginate rafts (polysaccharide polymers that precipitate into a low-density viscous gel when they contact gastric acid) have been reported to form at the acid pocket, an unbuffered pool of acid that floats on top of ingested food and causes postprandial acid reflux. We studied the location of an alginate formulation in relation to the acid pocket and the corresponding effects on reflux parameters and acid pocket positioning in patients with gastroesophageal reflux disease (GERD). We randomly assigned patients with symptomatic GERD and large hiatal hernias to groups who were given either (111)In-labeled alginate-antacid (n = 8, Gaviscon Double Action Liquid) or antacid (n = 8, Antagel) after a standard meal. The relative positions of labeled alginate and acid pocket were analyzed for 2 hours by using scintigraphy; reflux episodes were detected by using high-resolution manometry and pH-impedance monitoring. The alginate-antacid label localized to the acid pocket. The number of acid reflux episodes was significantly reduced in patients receiving alginate-antacid (3.5; range, 0-6.5; P = .03) compared with those receiving antacid (15; range, 5-20), whereas time to acid reflux was significantly increased in patients receiving alginate-antacid (63 minutes; range, 23-92) vs those receiving antacid (14 minutes; range, 9-23; P = .01). The acid pocket was located below the diaphragm in 71% of patients given alginate-antacid vs 21% of those given antacid (P = .08). There was an inverse correlation between a subdiaphragm position of the acid pocket and acid reflux (r = -0.76, P < .001). In a study of 16 patients with GERD, we observed that the alginate-antacid raft localizes to the postprandial acid pocket and displaces it below the diaphragm to reduce postprandial acid reflux. These findings indicate the importance of the acid pocket in GERD pathogenesis and establish alginate-antacid as an appropriate therapy for postprandial acid reflux. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Preparation of donut-shaped starch microparticles by aqueous-alcoholic treatment.

PubMed

Farrag, Yousof; Sabando, Constanza; Rodríguez-Llamazares, Saddys; Bouza, Rebeca; Rojas, Claudio; Barral, Luís

2018-04-25

A simple method for producing donut-shaped starch microparticles by adding ethanol to a heated aqueous slurry of corn starch is presented. The obtained microparticles were analysed by SEM, XRD and DSC. The average size of microparticles was 14.1 ± 0.3 μm with holes of an average size of 4.6 ± 0.2 μm. The crystalline arrangement of the microparticles was of a V-type single helix. The change in crystallinity from A-type of the starch granules to a more open structure, where water molecules could penetrate easier within the microparticles, substantially increased their solubility and swelling power. The microparticles exhibited a higher gelatinization temperature and a lower gelatinization enthalpy than did the starch granules. The donut-shaped microparticles were stable for more than 18 months and can be used as a carrier of an active compound or as a filler in bioplastics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microparticles of Aloe vera/vitamin E/chitosan: microscopic, a nuclear imaging and an in vivo test analysis for burn treatment.

PubMed

Pereira, Gabriela Garrastazu; Santos-Oliveira, Ralph; Albernaz, Martha S; Canema, Daniel; Weismüller, Gilberto; Barros, Eduardo Bede; Magalhães, Luciana; Lima-Ribeiro, Maria Helena Madruga; Pohlmann, Adriana Raffin; Guterres, Silvia S

2014-02-01

The use of drug-loaded nanoparticles and microparticles has been increasing, especially for cosmetic and drug delivery purposes. In this work, a new microparticle formulation was developed for use in the healing process of skin burns in a composition of Aloe vera/vitamin E/chitosan. In order to observe the morphological properties, Raman and atomic force microscopy evaluation were performed. The biodistribution studies were analyzed by using a nuclear methodology, labeling the microparticles with Technetium-99m and in vivo test was procedure to analyzed the cicatrization process. The results of AFM analysis show the formation and the adherence property of the microparticles. Raman analyses show the distribution of each component in the microparticle. The nuclear method used shows that the biodistribution of the microparticles remained in the skin. The in vivo cicatrization test showed that the poloxamer gel containing the microparticles make a better cicatrization in relation to the other formulations tested. Copyright © 2013 Elsevier B.V. All rights reserved.

Chitosan microparticles for sustaining the topical delivery of minoxidil sulphate.

PubMed

Gelfuso, Guilherme Martins; Gratieri, Taís; Simão, Patrícia Sper; de Freitas, Luís Alexandre Pedro; Lopez, Renata Fonseca Vianna

2011-01-01

Given the hypothesis that microparticles can penetrate the skin barrier along the transfollicular route, this work aimed to obtain and characterise chitosan microparticles loaded with minoxidil sulphate (MXS) and to study their ability to sustain the release of the drug, attempting a further application utilising them in a targeted delivery system for the topical treatment of alopecia. Chitosan microparticles, containing different proportions of MXS/polymer, were prepared by spray drying and were characterised by yield, encapsulation efficiency, size and morphology. Microparticles selected for further studies showed high encapsulation efficiency (∼82%), a mean diameter of 3.0 µm and a spherical morphology without porosities. When suspended in an ethanol/water solution, chitosan microparticles underwent instantaneous swelling, increasing their mean diameter by 90%. Release studies revealed that the chitosan microparticles were able to sustain about three times the release rate of MXS. This feature, combined with suitable size, confers to these microparticles the potential to target and improve topical therapy of alopecia with minoxidil.

Optimized preparation of in situ forming microparticles for the parenteral delivery of vinpocetine.

PubMed

Li, Jizhong; Chen, Fei; Hu, Chanjuan; He, Ling; Yan, Keshu; Zhou, Liying; Pan, Weisan

2008-06-01

A spherical symmetric design-response surface methodology was applied to optimize the preparation of vinpocetine-loaded poly(D,L-lactide-co-glycolide) PLGA in situ forming microparticles (ISM system). The influence of the ratio of PLGA to vinpocetine (w/w), the concentration of Tween 80 (w/v) and the volume of propylene glycol on the burst release, medium particle diameter and size distribution was evaluated. Scan electron microscopy of the optimized in situ microparticles exhibited spherical shape, and vinpocetine-loading mainly inside the microparticles. The data showed that the release of vinpocetine from in situ microparticles in vitro and in vivo lasted about 40 d. In vivo pharmacokinetic characteristics of the optimized in situ microparticles was assessed after they were intramuscularly injected into rats. HPLC method was used to determine the plasma concentration of vinpocetine. The absolute bioavailability of vinpocetine in the microparticles was 27.6% in rats, which suggested that PLGA in situ microparticles were a valuable system for the delivery of vinpocetine.

Electrospray of multifunctional microparticles for image-guided drug delivery

NASA Astrophysics Data System (ADS)

Zhang, Leilei; Yan, Yan; Mena, Joshua; Sun, Jingjing; Letson, Alan; Roberts, Cynthia; Zhou, Chuanqing; Chai, Xinyu; Ren, Qiushi; Xu, Ronald

2012-03-01

Anti-VEGF therapies have been widely explored for the management of posterior ocular disease, like neovascular age-related macular degeneration (AMD). Loading anti-VEGF therapies in biodegradable microparticles may enable sustained drug release and improved therapeutic outcome. However, existing microfabrication processes such as double emulsification produce drug-loaded microparticles with low encapsulation rate and poor antibody bioactivity. To overcome these limitations, we fabricate multifunctional microparticles by both single needle and coaxial needle electrospray. The experimental setup for the process includes flat-end syringe needles (both single needle and coaxial needle), high voltage power supplies, and syringe pumps. Microparticles are formed by an electrical field between the needles and the ground electrode. Droplet size and morphology are controlled by multiple process parameters and material properties, such as flow rate and applied voltage. The droplets are collected and freezing dried to obtain multifunctional microparticles. Fluorescent beads encapsulated poly(DL-lactide-co-glycolide) acid (PLGA) microparticles are injected into rabbits eyes through intravitreal injection to test the biodegradable time of microparticles.

Novel hierarchical microparticles super-assembled from nanoparticles with the induction of casein micelles

NASA Astrophysics Data System (ADS)

Xiong, Xiaopeng; Duan, Jiangjiang; Wang, Yong; Yu, Zhaoju

2013-08-01

We have demonstrated a solution-based synthesis of novel waxberry-like hierarchical ZnO microparticles in the presence casein micelles under mild conditions. The microstructures of the sub-micrometer-sized hierarchical microparticles were characterized, and the synthesis conditions were optimized. The formation mechanism of the hierarchical microparticle was analyzed through control experiments. The hierarchical ZnO microparticles are found to be super-assemblies of 30-70 nm ZnO nanoparticles, which are thought to be based on casein micelle induction followed by Ostwald ripening. In the same manner, copper-based hierarchical microparticles with a similar morphology have also been successfully synthesized. By controlling the synthetic time or temperature, solid or hollow microparticles can be fabricated. The narrowly distributed ZnO microparticles have a high specific surface area, exhibiting great potential application in fields such as photocatalytic and energy conversion. Our findings may meanwhile open a new bottom-up strategy in order to construct structurally sophisticated nanomaterials.

Immunogenicity and Protection of Oral Influenza Vaccines Formulated into Microparticles

PubMed Central

SHASTRI, PRATHAP NAGARAJA; KIM, MIN-CHUL; QUAN, FU-SHI; D’SOUZA, MARTIN J.; KANG, SANG-MOO

2017-01-01

Influenza is a deadly disease affecting humans and animals. It is recommended that every individual should be vaccinated annually against influenza. Considering the frequency of administration of this vaccine, we have explored the oral route of vaccination with a microparticulate formulation. Microparticles containing inactivated influenza A/PR/34/8 H1N1 virus with Eudragit S and trehalose as a matrix were prepared using the Buchi spray dryer. Particle size distribution of microparticles was measured and the bioactivity of vaccine in a microparticle form was analyzed using a hemagglutination activity test. Furthermore, the efficacy of microparticle vaccines was evaluated in vivo in Balb/c mice. Analysis of serum samples showed that microparticles resulted in enhanced antigen-specific immunoglobulin G (IgG), IgG1, and IgG2a antibodies. Upon challenge with homologous and heterologous influenza viruses, microparticle vaccines showed significantly increased levels of protection. Use of microparticles to deliver vaccines could be a promising tool for the development of an oral influenza vaccine. PMID:22711602

Development of nanocomposites based on hydroxyapatite/sodium alginate: Synthesis and characterisation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rajkumar, M.; Meenakshisundaram, N.; Rajendran, V., E-mail: veerajendran@gmail.com

2011-05-15

In this study, a novel method was used to produce a nanostructured composite consisting of hydroxyapatite and sodium alginate by varying the composition of sodium alginate. The structure, morphology, simulated body fluid response and mechanical properties of the synthesised nanocomposites were characterised. From X-ray diffraction analysis, an increase in crystallite size and degree of crystallinity with an increase in the composition of sodium alginate up to 1.5 wt.% was observed. Further, it was found to decrease with an increase in the composition of sodium alginate. A notable peak shift from 1635 to 1607 cm{sup -1} and 1456 to 1418 cm{supmore » -1} in the Fourier transform infrared spectra of the nanocomposite was observed towards the lower wave number side when compared with pure hydroxyapatite. It reveals a strong interaction between the positively charged calcium (Ca{sup 2+}) and the negatively charged carboxyl group (COO{sup -}) in sodium alginate. Transmission electron microscopy images of pure hydroxyapatite showed a short nanorod-like morphology with an average particle size of 13 nm. Bioresorbability of the samples was observed by immersing them in simulated body fluid medium for 14 days to evaluate the changes in pH and Ca{sup 2+} ion strength. Microhardness shows an increasing trend with an increase in the composition of sodium alginate from 1.5 to 3.0 wt.%, which is similar to that in the density. - Research Highlights: {yields} We have prepared nanohydroxyapatite/sodium alginate as a composite. {yields} Effect of sodium alginate on the properties of nanohydrroxyapatite has been studied. {yields} The sodium alginate ranges from 0 to 3.75 wt.% has been used. {yields} Composites show improved biological and mechanical properties.« less

Fabrication of individual alginate-TCP scaffolds for bone tissue engineering by means of powder printing.

PubMed

Castilho, Miguel; Rodrigues, Jorge; Pires, Inês; Gouveia, Barbara; Pereira, Manuel; Moseke, Claus; Groll, Jürgen; Ewald, Andrea; Vorndran, Elke

2015-01-06

The development of polymer-calcium phosphate composite scaffolds with tailored architectures and properties has great potential for bone regeneration. Herein, we aimed to improve the functional performance of brittle ceramic scaffolds by developing a promising biopolymer-ceramic network. For this purpose, two strategies, namely, direct printing of a powder composition consisting of a 60:40 mixture of α/β-tricalcium phosphate (TCP) powder and alginate powder or vacuum infiltration of printed TCP scaffolds with an alginate solution, were tracked. Results of structural characterization revealed that the scaffolds printed with 2.5 wt% alginate-modified TCP powders presented a uniformly distributed and interfusing alginate TCP network. Mechanical results indicated a significant increase in strength, energy to failure and reliability of powder-modified scaffolds with an alginate content in the educts of 2.5 wt% when compared to pure TCP, as well as to TCP scaffolds containing 5 wt% or 7.5 wt% in the educts, in both dry and wet states. Culture of human osteoblast cells on these scaffolds also demonstrated a great improvement of cell proliferation and cell viability. While in the case of powder-mixed alginate TCP scaffolds, isolated alginate gels were formed between the calcium phosphate crystals, the vacuum-infiltration strategy resulted in the covering of the surface and internal pores of the TCP scaffold with a thin alginate film. Furthermore, the prediction of the scaffolds' critical fracture conditions under more complex stress states by the applied Mohr fracture criterion confirmed the potential of the powder-modified scaffolds with 2.5 wt% alginate in the educts as structural biomaterial for bone tissue engineering.

Biomaterials for the Decorporation of Sr-85 in the Rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levitskaia, Tatiana G.; Creim, Jeffrey A.; Curry, Terry L.

2010-09-01

Although four stable isotopes of strontium occur naturally, strontium-90 is produced by nuclear fission and is present in surface soil around the world as a result of fallout from atmospheric nuclear weapons tests. It can easily transfer to man in the event of a nuclear/radiological emergency or through the plant-animal-human food chain causing long-term exposures. Strontium is chemically and biologically similar to calcium, and is incorporated primarily into bone following internal deposition. Alginic acid (alginate) obtained from seaweed (kelp) extract selectively binds ingested strontium in the GI tract blocking its systemic uptake and reducing distribution to bone in rats, whilemore » other natural polysaccharides including chitosan and hyaluronic acid had little in vivo affinity for strontium. Alginate exhibits the unique ability to discriminate between strontium and calcium and has been previously shown to reduce intestinal absorption and skeletal retention of strontium without changing calcium metabolism. In our studies, the effect of commercially available alginate on strontium intestinal absorption was examined. One problem associated with alginate treatment is its limited solubility and gel formation in water. The aqueous solubility of sodium alginate was improved in a sodium chloride/sodium bicarbonate electrolyte solution containing low molecular weight polyethylene glycol (PEG). Furthermore, oral administration of the combined alginate/electrolyte//PEG solution synergistically accelerated removal of internal strontium in rats when compared to treatment with individual sodium alginate/electrolyte or electrolyte/PEG solutions. Importantly, both alginate and PEG are nontoxic, readily available materials that can be easily administered orally in case of a national emergency when potentially large numbers of the population may require medical treatment for internal depositions. Our results suggest further studies to optimize in vivo decorporation performance of engineered alginate material via modification of its chemical and physicochemical properties is warranted.« less

Evolution of Sulfobacillus thermosulfidooxidans secreting alginate during bioleaching of chalcopyrite concentrate.

PubMed

Yu, R-L; Liu, A; Liu, Y; Yu, Z; Peng, T; Wu, X; Shen, L; Liu, Y; Li, J; Liu, X; Qiu, G; Chen, M; Zeng, W

2017-06-01

To explore the distribution disciplinarian of alginate on the chalcopyrite concentrate surface during bioleaching. The evolution of Sulfobacillus thermosulfidooxidans secreting alginate during bioleaching of chalcopyrite concentrate was investigated through gas chromatography coupled with mass spectrometry (GC-MS) and confocal laser scanning microscope (CLSM), and the critical synthetic genes (algA, algC, algD) of alginate were analysed by real-time polymerase chain reaction (RT-PCR). The GC-MS analysis results indicated that there was a little amount of alginate formed on the mineral surface at the early stage, while increasing largely to the maximum value at the intermediate stage, and then kept a stable value at the end stage. The CLSM analysis of chalcopyrite slice showed the same variation trend of alginate content on the mineral surface. Furthermore, the RT-PCR results showed that during the early stage of bioleaching, the expressions of the algA, algC and the algD genes were all overexpressed. However, at the final stage, the algD gene expression decreased in a large scale, and the algA and algC decreased slightly. This expression pattern was attributed to the fact that algA and algC genes were involved in several biosynthesis reactions, but the algD gene only participated in the alginate biosynthesis and this was considered as the key gene to control alginate synthesis. The content of alginate on the mineral surface increased largely at the beginning of bioleaching, and remained stable at the end of bioleaching due to the restriction of algD gene expression. Our findings provide valuable information to explore the relationship between alginate formation and bioleaching of chalcopyrite. © 2017 The Society for Applied Microbiology.

External and Intraparticle Diffusion of Coumarin 102 with Surfactant in the ODS-silica Gel/water System by Single Microparticle Injection and Confocal Fluorescence Microspectroscopy.

PubMed

Nakatani, Kiyoharu; Matsuta, Emi

2015-01-01

The release mechanism of coumarin 102 from a single ODS-silica gel microparticle into the water phase in the presence of Triton X-100 was investigated by confocal fluorescence microspectroscopy combined with the single microparticle injection technique. The release rate significantly depended on the Triton X-100 concentration in the water phase and was not limited by diffusion in the pores of the microparticle. The release rate constant was inversely proportional to the microparticle radius squared, indicating that the rate-determining step is the external diffusion between the microparticle and the water phase.

Characterization of nitric oxide-releasing microparticles for the mucosal delivery.

PubMed

Yoo, Jin-Wook; Lee, Jae-Suk; Lee, Chi H

2010-03-15

For the treatment of female sexual arousal disorder (FSAD), we developed microparticles made of PLGA containing nitric oxide (NO) donor (DETA NONOate) to efficiently deliver NO to vaginal mucosa. The NO-releasing microparticles were prepared by various emulsion methods. SEM and DSC studies were performed to examine the microparticles. The release studies were conducted under various conditions to optimize the loading dose in the microparticles. NO diffusivity through vaginal epithelial cells was evaluated and pharmacological activity of NO-releasing microparticles was examined by assessment of intracellular cGMP level in vaginal cells. Through the modified double emulsion solvent evaporation method (w/o/w(a)), the acid labile DETA NONOate was stabilized during the fabrication process and homogenous morphology and high entrapment efficiency were achieved. DETA NONOate was protected under the acidic conditions of the vagina and NO was released from the microparticles in a controlled manner. A significant amount of NO produced from DETA NONOate penetrated through the vaginal epithelial cells. The intracellular cGMP level increased with the treatment of NO-releasing microparticles in vaginal cells. These findings suggest that NO-releasing microparticles could improve the vaginal blood perfusion and open up the possibilities of novel treatment of FSAD. (c) 2009 Wiley Periodicals, Inc.

Cell-derived microparticles and the lung.

PubMed

Nieri, Dario; Neri, Tommaso; Petrini, Silvia; Vagaggini, Barbara; Paggiaro, Pierluigi; Celi, Alessandro

2016-09-01

Cell-derived microparticles are small (0.1-1 μm) vesicles shed by most eukaryotic cells upon activation or during apoptosis. Microparticles carry on their surface, and enclose within their cytoplasm, molecules derived from the parental cell, including proteins, DNA, RNA, microRNA and phospholipids. Microparticles are now considered functional units that represent a disseminated storage pool of bioactive effectors and participate both in the maintenance of homeostasis and in the pathogenesis of diseases. The mechanisms involved in microparticle generation include intracellular calcium mobilisation, cytoskeleton rearrangement, kinase phosphorylation and activation of the nuclear factor-κB. The role of microparticles in blood coagulation and inflammation, including airway inflammation, is well established in in vitro and animal models. The role of microparticles in human pulmonary diseases, both as pathogenic determinants and biomarkers, is being actively investigated. Microparticles of endothelial origin, suggestive of apoptosis, have been demonstrated in the peripheral blood of patients with emphysema, lending support to the hypothesis that endothelial dysfunction and apoptosis are involved in the pathogenesis of the disease and represent a link with cardiovascular comorbidities. Microparticles also have potential roles in patients with asthma, diffuse parenchymal lung disease, thromboembolism, lung cancer and pulmonary arterial hypertension. Copyright ©ERS 2016.

Injectable nanosilica-chitosan microparticles for bone regeneration applications.

PubMed

Gaihre, Bipin; Lecka-Czernik, Beata; Jayasuriya, Ambalangodage C

2018-01-01

This study was aimed at assessing the effects of silica nanopowder incorporation into chitosan-tripolyphosphate microparticles with the ultimate goal of improving their osteogenic properties. The microparticles were prepared by simple coacervation technique and silica nanopowder was added at 0% (C), 2.5% (S1), 5% (S2) and 10% (S3) (w/w) to chitosan. We observed that this simple incorporation of silica nanopowder improved the growth and proliferation of osteoblasts along the surface of the microparticles. In addition, the composite microparticles also showed the increased expression of alkaline phosphatase and osteoblast specific genes. We observed a significant increase ( p < 0.05) in the expression of alkaline phosphatase by the cells growing on all sample groups compared to the control (C) groups at day 14. The morphological characterization of these microparticles through scanning electron microscopy showed that these microparticles were well suited to be used as the injectable scaffolds with perfectly spherical shape and size. The incorporation of silica nanopowder altered the nano-roughness of the microparticles as observed through atomic force microscopy scans with roughness values going down from C to S3. The results in this study, taken together, show the potential of chitosan-tripolyphosphate-silica nanopowder microparticles for improved bone regeneration applications.

Effect of short-chain fatty acids on the formation of amylose microparticles by amylosucrase.

PubMed

Lim, Min-Cheol; Park, Kyu-Hwan; Choi, Jong-Hyun; Lee, Da-Hee; Letona, Carlos Andres Morales; Baik, Moo-Yeol; Park, Cheon-Seok; Kim, Young-Rok

2016-10-20

Amylose microparticles can be produced by self-assembly of amylose molecules through an amylosucrase-mediated synthesis. Here we investigated the role of short-chain fatty acids in the formation of amylose microparticles and the fate of these fatty acids at the end of the reaction. The rate of self-assembly and production yields of amylose microparticles were significantly enhanced in the presence of fatty acids. The effect was dependent on the length of the fatty acid carbon tail; butanoic acid (C4) was the most effective, followed by hexanoic acid (C6) and octanoic acid (C8). The amylose microparticles were investigated by carrying out SEM, XRD, Raman, NMR, FT-IR and DSC analysis. The size, morphology and crystal structure of the resulting amylose microparticles were comparable with those of amylose microparticles produced without fatty acids. The results indicated the carboxyl group of the fatty acid to be responsible for promoting the self-assembly of amylose chains to form microparticles. The fatty acids were eventually removed from the microstructure through the tight association of amylose double helices to form the amylose microparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improving the performance of transglutaminase-crosslinked microparticles for enteric delivery.

PubMed

Tello, Fernando; Prata, Ana S; Rodrigues, Rodney A F; Sartoratto, Adilson; Grosso, Carlos R F

2016-10-01

Various agents for cross-linking have been investigated for stabilizing and controlling the barrier properties of microparticles for enteric applications. Transglutaminase, in addition to being commercially available for human consumption, presents inferior cross-linking action compared to glutaraldehyde. In this study, the intensity of this enzymatic cross-linking was investigated in microparticles obtained by complex coacervation between gelatin and gum Arabic. The effectiveness of cross-linking in these microparticles was evaluated based on swelling, release of a model substance (parika oleoresin: colored and hydrophobic) and gastrointestinal assays. The cross-linked microparticles remained intact under gastric conditions, whereas the uncross-linked microparticles have been dissolved. However, all of the microparticles have been dissolved under intestinal conditions. The amount of oily core that was released decreased as the amount of transglutaminase increased. For the most efficient microparticles (50U/g of protein), the performance was improved by increasing the pH of cross-linking from 4.0 to 6.0, resulting in a release of 17.1% rather than 32.3% of the core material. These results were considerably closer to the 10.3% of core material released by glutaraldehyde-cross-linked microparticles (1mM/g of protein). Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of anti-TNF-α agents on circulating endothelial-derived and platelet-derived microparticles in psoriasis.

PubMed

Pelletier, Fabien; Garnache-Ottou, Francine; Biichlé, Sabeha; Vivot, Aurore; Humbert, Philippe; Saas, Philippe; Seillès, Estelle; Aubin, François

2014-12-01

Psoriasis involves TNF-α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti-TNF-α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti-TNF-α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti-TNF-α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti-TNF-α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel cryomilled physically cross-linked biodegradable hydrogel microparticles as carriers for inhalation therapy.

PubMed

El-Sherbiny, I M; Smyth, H D C

2010-01-01

In this study, novel biodegradable physically cross-linked hydrogel microparticles were developed and evaluated in-vitro as potential carriers for inhalation therapy. These hydrogel microparticles were prepared to be respirable (desired aerodynamic size) when dry and also designed to avoid the macrophage uptake (attain large swollen size once deposited in lung). The swellable microparticles, prepared using cryomilling, were based on Pluronic® F-108 in combination with PEG grafted onto both chitosan (Cs) and its N-phthaloyl derivative (NPHCs). Polymers synthesized in the study were characterized using EA, FTIR, 2D-XRD and DSC. Morphology, particle size, density, biodegradation and moisture content of the microparticles were quantified. Swelling characteristics for both drug-free and drug-loaded microparticles showed excellent size increases (between 700-1300%) and the release profiles indicated sustained release could be achieved for up to 20 days. The respirable microparticles showed drug loading efficiency up to 92%. The enzymatic degradation of developed microparticles started within the first hour and only ∼10% weights were remaining after 10 days. In conclusion, these respirable microparticles demonstrated promising in-vitro performance for potential sustained release vectors in pulmonary drug delivery.

Dynamic release and clearance of circulating microparticles during cardiac stress.

PubMed

Augustine, Daniel; Ayers, Lisa V; Lima, Eduardo; Newton, Laura; Lewandowski, Adam J; Davis, Esther F; Ferry, Berne; Leeson, Paul

2014-01-03

Microparticles are cell-derived membrane vesicles, relevant to a range of biological responses and known to be elevated in cardiovascular disease. To investigate microparticle release during cardiac stress and how this response differs in those with vascular disease. We measured a comprehensive panel of circulating cell-derived microparticles by a standardized flow cytometric protocol in 119 patients referred for stress echocardiography. Procoagulant, platelet, erythrocyte, and endothelial but not leukocyte, granulocyte, or monocyte-derived microparticles were elevated immediately after a standardized dobutamine stress echocardiogram and decreased after 1 hour. Twenty-five patients developed stress-induced wall motion abnormalities suggestive of myocardial ischemia. They had similar baseline microparticle levels to those who did not develop ischemia, but, interestingly, their microparticle levels did not change during stress. Furthermore, no stress-induced increase was observed in those without inducible ischemia but with a history of vascular disease. Fourteen patients subsequently underwent coronary angiography. A microparticle rise during stress echocardiography had occurred only in those with normal coronary arteries. Procoagulant, platelet, erythrocyte, and endothelial microparticles are released during cardiac stress and then clear from the circulation during the next hour. This stress-induced rise seems to be a normal physiological response that is diminished in those with vascular disease.

Polygalacturonase production by calcium alginate immobilized Enterobacter aerogenes NBO2 cells.

PubMed

Darah, I; Nisha, M; Lim, Sheh-Hong

2015-03-01

Bacterial cells of Enterobacter aerogenes NBO2 were entrapped in calcium alginate beads in order to enhance polygalacturonase production compared to free cells. The optimized condition of 5 % (w/v) sodium alginate concentration, agitation speed of 250 rpm, and 15 beads of calcium alginate with inoculum size of 4 % (v/v; 5.4 × 10(7) cells/ml) produced 23.48 U/mL of polygalacturonase compared to free cells of 18.54 U/ml. There was about 26.6 % increment in polygalaturonase production. However, in this study, there was 296.6 % of increment in polygalacturonase production after improvement parameters compared to before improvement parameters of calcium alginate bead immobilization cells (5.92 U/ml). This research has indicated that optimized physical parameters of calcium alginate bead immobilization cells have significantly enhanced the production of polygalacturonase.

Chitosan Enriched Three-Dimensional Matrix Reduces Inflammatory and Catabolic Mediators Production by Human Chondrocytes

PubMed Central

Oprenyeszk, Frederic; Sanchez, Christelle; Dubuc, Jean-Emile; Maquet, Véronique; Henrist, Catherine; Compère, Philippe; Henrotin, Yves

2015-01-01

This in vitro study investigated the metabolism of human osteoarthritic (OA) chondrocytes encapsulated in a spherical matrix enriched of chitosan. Human OA chondrocytes were encapsulated and cultured for 28 days either in chitosan-alginate beads or in alginate beads. The beads were formed by slowly passing dropwise either the chitosan 0.6%–alginate 1.2% or the alginate 1.2% solution through a syringe into a 102 mM CaCl2 solution. Beads were analyzed histologically after 28 days. Interleukin (IL)-6 and -8, prostaglandin (PG) E2, matrix metalloproteinases (MMPs), hyaluronan and aggrecan were quantified directly in the culture supernatant by specific ELISA and nitric oxide (NO) by using a colorimetric method based on the Griess reaction. Hematoxylin and eosin staining showed that chitosan was homogeneously distributed through the matrix and was in direct contact with chondrocytes. The production of IL-6, IL-8 and MMP-3 by chondrocytes significantly decreased in chitosan-alginate beads compared to alginate beads. PGE2 and NO decreased also significantly but only during the first three days of culture. Hyaluronan and aggrecan production tended to increase in chitosan-alginate beads after 28 days of culture. Chitosan-alginate beads reduced the production of inflammatory and catabolic mediators by OA chondrocytes and tended to stimulate the synthesis of cartilage matrix components. These particular effects indicate that chitosan-alginate beads are an interesting scaffold for chondrocytes encapsulation before transplantation to repair cartilage defects. PMID:26020773

Microfluidics-assisted generation of stimuli-responsive hydrogels based on alginates incorporated with thermo-responsive and amphiphilic polymers as novel biomaterials.

PubMed

Karakasyan, C; Mathos, J; Lack, S; Davy, J; Marquis, M; Renard, D

2015-11-01

We used a droplet-based microfluidics technique to produce monodisperse responsive alginate-block-polyetheramine copolymer microgels. The polyetheramine group (PEA), corresponding to a propylene oxide /ethylene oxide ratio (PO/EO) of 29/6 (Jeffamine(®) M2005), was condensed, via the amine link, to alginates with various mannuronic/guluronic acids ratios and using two alginate:jeffamine mass ratios. The size of the grafted-alginate microgels varied from 60 to 80 μm depending on the type of alginate used and the degree of substitution. The droplet-based microfluidics technique offered exquisite control of both the dimension and physical chemical properties of the grafted-alginate microgels. These microgels were therefore comparable to isolated grafted-alginate chains in retaining both their amphiphilic and thermo-sensitive properties. Amphiphilicity was demonstrated at the oil-water interface where grafted-alginate microgels were found to decrease interfacial tension by ∼ 50%. The thermo-sensitivity of microgels was clearly demonstrated and a 10 to 20% reduction in size between was evidenced on increasing the temperature above the lower critical solution temperature (TLCST) of Jeffamine. In addition, the reversibility of thermo-sensitivity was demonstrated by studying the oil-water affinity of microgels with temperature after Congo red labeling. Finally, droplet-based microfluidics was found to be a good and promising tool for generating responsive biobased hydrogels for drug delivery applications and potential new colloidal stabilizers for dispersed systems such as Pickering emulsions. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation, In Vitro Characterization, and In Vivo Pharmacokinetic Evaluation of Respirable Porous Microparticles Containing Rifampicin

PubMed Central

Kundawala, Aliasgar; Patel, Vishnu; Patel, Harsha; Choudhary, Dhaglaram

2014-01-01

Abstract This study aimed to prepare and evaluate rifampicin microparticles for the lung delivery of rifampicin as respirable powder. The microparticles were prepared using chitosan by the spray-drying method and evaluated for aerodynamic properties and pulmonary drug absorption. To control the drug release, tripoly-phosphate in different concentrations 0.6, 0.9, 1.2, and 1.5 was employed to get a sustained drug release profile. The microparticles were evaluated for drug loading, % entrapment efficiency, tapped density, morphological characteristics, and in vitro drug release studies. Aerosol properties were determined using the Andersen cascade impactor. Porous microparticles with particle sizes (d0.5) less than 10 μm were obtained. The entrapment of rifampicin in microparticles was up to 72%. In vitro drug release suggested that the crosslinked microparticles showed sustained release for more than 12 hrs. The drug release rate was found to be decreased as the TPP concentration was increased. The microparticles showed a fine particle fraction in the range of 55–63% with mass median aerodynamic diameter (MMAD) values below 3 μm. The in vivo pulmonary absorption of the chitosan microparticles suggested a sustained drug release profile up to 72 hrs with an elimination rate of 0.010 per hr. The studies revealed that the spray-dried porous microparticles have suitable properties to be used as respirable powder in rifampicin delivery to the lungs. PMID:25853075

Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine.

PubMed Central

Singh, M; Li, X M; Wang, H; McGee, J P; Zamb, T; Koff, W; Wang, C Y; O'Hagan, D T

1997-01-01

Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization. PMID:9125552

Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.

PubMed

György, Bence; Pálóczi, Krisztina; Kovács, Alexandra; Barabás, Eszter; Bekő, Gabriella; Várnai, Katalin; Pállinger, Éva; Szabó-Taylor, Katalin; Szabó, Tamás G; Kiss, Attila A; Falus, András; Buzás, Edit I

2014-02-01

Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Increased circulating leukocyte-derived microparticles in ischemic cerebrovascular disease.

PubMed

He, Zhangping; Tang, Yanyan; Qin, Chao

2017-06-01

Circulating leukocyte-derived microparticles act as proinflammatory mediators that reflect vascular inflammation. In this study, we examined the hypothesis that the quantity of leukocyte-derived microparticles is increased in patients with ischemic cerebrovascular diseases, and investigated utility of various phenotypes of leukocyte-derived microparticles as specific biomarkers of vascular inflammation injury. Additionally we focused on identifying leukocyte-derived microparticles that may be correlated with stroke severity in acute ischemic stroke patients. The plasma concentration of leukocyte-derived microparticles obtained by a series of centrifugations of 76 consecutive patients with ischemic cerebrovascular diseases and 70 age-, sex-, and race-matched healthy controls were determined by flow cytometry. Significantly elevated numbers of leukocyte (CD45+), monocyte (CD14+), lymphocyte (CD4+), granulocyte (CD15+) derived microparticles were found in the plasma samples of patients ischemic cerebrovascular diseases, compared to healthy controls (p<0.05). Furthermore, the plasma levels of CD14+ microparticles were significantly correlated with stroke severity (r=0.355, p=0.019), cerebral vascular stenosis severity (r=0.255, p=0.025) and stroke subtype (r=0.242, p=0.036). No association with stroke was observed for other leukocyte-derived phenotypes. These results demonstrate that circulating leukocyte-derived microparticles amounts are increased in patients with ischemic cerebrovascular diseases, compared with healthy controls. As proinflammatory mediators, leukocyte-derived microparticles may contribute to vascular inflammatory and the inflammatory process in acute ischemic stroke. Levels of CD14+ microparticles may be a promising biomarker of ischemic severity and outcome of stroke in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Procoagulant effects of lung cancer chemotherapy: impact on microparticles and cell-free DNA.

PubMed

Lysov, Zakhar; Dwivedi, Dhruva J; Gould, Travis J; Liaw, Patricia C

2017-01-01

Lung cancer is the second leading type of cancer, with venous thromboembolism being the second leading cause of death. Studies have shown increased levels of microparticles and cell-free DNA (CFDNA) in cancer patients, which can activate coagulation through extrinsic and intrinsic pathways, respectively. However, the impact of lung cancer chemotherapy on microparticle and/or CFDNA generation is not completely understood. The aim of the study was to study the effects of platinum-based chemotherapeutic agents on generation of procoagulant microparticles and CFDNA in vitro and in vivo. Microparticles were isolated from chemotherapy-treated monocytes, human umbilical vein endothelial cells, or cancer cells. Tissue factor (TF) and phosphatidylserine levels were characterized and thrombin/factor Xa generation assays were used to determine microparticle procoagulant activity. CFDNA levels were isolated from cell supernatants and plasma. A murine xenograft model of human lung carcinoma was used to study the procoagulant effects of TF microparticles and CFDNA in vivo. In vitro, platinum-based chemotherapy induced TF/phosphatidylserine microparticle shedding from A549 and A427 lung cancers cells, which enhanced thrombin generation in plasma in a FVII-dependent manner. CFDNA levels were increased in supernatants of chemotherapy-treated neutrophils and plasma of chemotherapy-treated mice. TF microparticles were elevated in plasma of chemotherapy-treated tumour-bearing mice. Plasma CFDNA levels are increased in chemotherapy-treated tumour-free mice and correlate with increased thrombin generation. In tumour-bearing mice, chemotherapy increases plasma levels of CFDNA and TF/phosphatidylserine microparticles. Platinum-based chemotherapy induces the shedding of TF/phosphatidylserine microparticles from tumour cells and the release of CFDNA from host neutrophils.

CIRCULATING MICROPARTICLES IN PATIENTS WITH ANTIPHOSPHOLIPID ANTIBODIES: CHARACTERIZATION AND ASSOCIATIONS

PubMed Central

Chaturvedi, Shruti; Cockrell, Erin; Espinola, Ricardo; Hsi, Linda; Fulton, Stacey; Khan, Mohammad; Li, Liang; Fonseca, Fabio; Kundu, Suman; McCrae, Keith R.

2014-01-01

The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte, platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-β2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2 hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R = 0.60, p=0.006) and IgM anti-beta2-glycoprotein I antibodies (R=0.58, p=0.006). The elevation of endothelial and platelet derived microparticles in patients with APS and their correlation with anti-β2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for β2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies. PMID:25467081

Fabrication of magnetic alginate beads with uniform dispersion of CoFe2O4 by the polydopamine surface functionalization for organic pollutants removal

NASA Astrophysics Data System (ADS)

Li, Xiaoli; Lu, Haijun; Zhang, Yun; He, Fu; Jing, Lingyun; He, Xinghua

2016-12-01

A simple and efficient method for production of magnetic composites by decorating CoFe2O4 with polydopamine (PDA) through oxidative polymerization of dopamine was conducted. Further, magnetic alginate beads with porous structure containing well-dispersed CoFe2O4-PDA were fabricated by ionic crosslinking technology. The resulting SA@CoFe2O4-PDA beads were characterized using scanning electron microscopy, Fourier transform infrared spectrometry, X-ray diffractometer, vibrating sample magnetometer and X-ray photoelectron spectroscopy. Adsorption potential of SA@CoFe2O4-PDA beads for organic dyes including Methylene Blue (MB), Crystal Violet (CV) and Malachite Green (MG) was evaluated. SA@CoFe2O4-PDA beads exhibited excellent adsorption performances due to the composite effect, large surface area and porous structure. Organic dyes could be removed from water solution with high efficiency in a wide pH range of 4.0-9.0. Moreover, it exhibited much higher adsorptivity towards MB and CV with the maximum adsorption capacities of 466.60 and 456.52 mg/g, respectively, which were much higher than that of MG (248.78 mg/g). Ca-electrolyte had obvious adverse effects on MB and CV adsorption than MG. FTIR and XPS demonstrated that carboxylate, catechol, hydroxyl and amine groups might be involved in adsorption of organic dyes. The characteristics of wide pH range, high adsorption capacity and convenient magnetic separation would make SA@CoFe2O4-PDA beads as effective adsorbent for removal of organic dyes from wastewater.

Alginate/Gelatin scaffolds incorporated with Silibinin-loaded Chitosan nanoparticles for bone formation in vitro.

PubMed

Leena, R S; Vairamani, M; Selvamurugan, N

2017-10-01

Silibinin is a plant derived flavonolignan known for its multiple biological properties, but its role in the promotion of bone formation has not yet been well studied. Moreover, the delivery of Silibinin is hindered by its complex hydrophobic nature, which limits its bioavailability. Hence, in this study, we fabricated a drug delivery system using chitosan nanoparticles loaded with Silibinin at different concentrations (20μM, 50μM, and 100μM). They were then incorporated into scaffolds containing Alginate and Gelatin (Alg/Gel) for the sustained and prolonged release of Silibinin. The Silibinin-loaded chitosan nanoparticles (SCN) were prepared using the ionic gelation technique, and the scaffolds (Alg/Gel-SCN) were synthesized by the conventional method of freeze drying. The scaffolds were subjected to physicochemical and material characterization studies. The addition of SCN did not affect the porosity of the scaffolds, yet increased the protein adsorption, degradation rates, and bio-mineralization. These scaffolds were biocompatible with mouse mesenchymal stem cells. The scaffolds loaded with 50μM Silibinin promoted osteoblast differentiation, which was determined at cellular and molecular levels. Recent studies indicated the role of microRNAs (miRNAs) in osteogenesis and we found that the Silibinin released from scaffolds regulated miRNAs that control the bone morphogenetic protein pathway. Hence, our results suggest the potential for sustained and prolonged release of Silibinin to promote bone formation and, thus, these Alg/Gel-SCN scaffolds may be candidates for bone tissue engineering applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Microencapsulation of Lactobacillus helveticus and Lactobacillus delbrueckii using alginate and gellan gum.

PubMed

Rosas-Flores, Walfred; Ramos-Ramírez, Emma Gloria; Salazar-Montoya, Juan Alfredo

2013-10-15

Sodium alginate (SA) at 2% (w/v) and low acylated gellan gum (LAG) at 0.2% (w/v) were used to microencapsulate Lactobacillus helveticus and Lactobacillus delbrueckii spp lactis by employing the internal ionic gelation technique through water-oil emulsions at three different stirring rates: 480, 800 and 1200 rpm. The flow behavior of the biopolymer dispersions, the activation energy of the emulsion, the microencapsulation efficiency, the size distribution, the microcapsules morphology and the effect of the stirring rate on the culture viability were analyzed. All of the dispersions exhibited a non-Newtonian shear-thinning flow behavior because the apparent viscosity decreased in value when the shear rate was increased. The activation energy was calculated using the Arrhenius-like equation; the value obtained for the emulsion was 32.59 kJ/mol. It was observed that at 400 rpm, the microencapsulation efficiency was 92.83%, whereas at 800 and 1200 rpm, the stirring rates reduced the efficiency to 15.83% and 4.56%, respectively, evidencing the sensitivity of the microorganisms to the shear rate (13.36 and 20.05 s(-1)). Both optical and scanning electron microscopy (SEM) showed spherical microcapsules with irregular topography due to the presence of holes on its surface. The obtained size distribution range was modified when the stirring rate was increased. At 400 rpm, bimodal behavior was observed in the range of 20-420 μm; at 800 and 1200 rpm, the behavior became unimodal and the range was from 20 to 200 μm and 20 to 160 μm, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

In vitro fermentation of alginate and its derivatives by human gut microbiota.

PubMed

Li, Miaomiao; Li, Guangsheng; Shang, Qingsen; Chen, Xiuxia; Liu, Wei; Pi, Xiong'e; Zhu, Liying; Yin, Yeshi; Yu, Guangli; Wang, Xin

2016-06-01

Alginate (Alg) has a long history as a food ingredient in East Asia. However, the human gut microbes responsible for the degradation of alginate and its derivatives have not been fully understood yet. Here, we report that alginate and the low molecular polymer derivatives of mannuronic acid oligosaccharides (MO) and guluronic acid oligosaccharides (GO) can be completely degraded and utilized at various rates by fecal microbiota obtained from six Chinese individuals. However, the derivative of propylene glycol alginate sodium sulfate (PSS) was not hydrolyzed. The bacteria having a pronounced ability to degrade Alg, MO and GO were isolated from human fecal samples and were identified as Bacteroides ovatus, Bacteroides xylanisolvens, and Bacteroides thetaiotaomicron. Alg, MO and GO can increase the production level of short chain fatty acids (SCFA), but GO generates the highest level of SCFA. Our data suggest that alginate and its derivatives could be degraded by specific bacteria in the human gut, providing the basis for the impacts of alginate and its derivates as special food additives on human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of cryopreservation and hypothermic storage on cell viability and enzyme activity in recombinant encapsulated cells overexpressing alpha-L-iduronidase.

PubMed

Mayer, Fabiana Quoos; Baldo, Guilherme; de Carvalho, Talita Giacomet; Lagranha, Valeska Lizzi; Giugliani, Roberto; Matte, Ursula

2010-05-01

Here, we show the effects of cryopreservation and hypothermic storage upon cell viability and enzyme release in alginate beads containing baby hamster kidney cells overexpressing alpha-L-iduronidase (IDUA), the enzyme deficient in mucopolysaccharidosis type I. In addition, we compared two different concentrations of alginate gel (1% and 1.5%) in respect to enzyme release from the beads and their shape and integrity. Our results indicate that in both alginate concentrations, the enzyme is released in lower amounts compared with nonencapsulated cells. Alginate 1% beads presented increased levels of IDUA release, although this group presented more deformities when compared with alginate 1.5% beads. Importantly, both encapsulated groups presented higher cell viability after long cryopreservation period and hypothermic storage. In addition, alginate 1.5% beads presented higher enzyme release after freezing protocols. Taken together, our findings suggest a benefic effect of alginate upon cell viability and functionality. These results may have important application for treatment of both genetic and nongenetic diseases using microencapsulation-based artificial organs.

Formation and cleaning function of physically cross-linked dual strengthened water-soluble chitosan-based core-shell particles.

PubMed

Dong, Yanrui; Xiao, Congming

2017-09-01

Facile and mild ionic cross-linking and freezing/thawing technologies were applied to prepare double strengthened core-shell particles by using water-soluble chitosan (WSC), sodium alginate (SA) and poly(vinyl alcohol) (PVA) as starting materials. The aqueous solution contained WSC and PVA was dropped in ethanol to form beads. The beads were converted into WSC/PVA hydrogel particles by being subjected to three freeze/thaw cycles. Subsequently, ionic cross-linked hydrogel layer was formed around each WSC/PVA particle to generate core-shell particulates. Fourier transform infrared spectra confirmed the combination among various components. Dynamic mechanical thermal analysis indicated that the storage modulus of the core-shell hydrogel was improved obviously. Thermogravimetric analysis exhibited the thermal stability of the particles was also enhanced by incorporation of PVA. It was found that the particles were able to adsorb carbon dioxide, lead ion and copper ion. The adsorption capacities of dry particles toward carbon dioxide, Pb(II) and Cu(II) could reach 199.62, 39.28 and 26.03mg/g, respectively. The rates of the particles for binding Pb(II) and Cu(II) at initial stage were 26.57 and 4.30%/min, respectively. These experimental results suggested that the particles were an efficient sorbent for removing hazardous substances such as carbon dioxide and heavy-metal ions. Copyright © 2017 Elsevier B.V. All rights reserved.

Cell-derived microparticles in the pathogenesis of cardiovascular disease: friend or foe?

PubMed

Tushuizen, Maarten E; Diamant, Michaela; Sturk, Augueste; Nieuwland, Rienk

2011-01-01

Microparticles are ascribed important roles in coagulation, inflammation, and endothelial function. These processes are mandatory to safeguard the integrity of the organism, and their derangements contribute to the development of atherosclerosis and cardiovascular disease. More recently, the presumed solely harmful role of microparticles has been challenged because microparticles may also be involved in the maintenance and preservation of cellular homeostasis and in promoting defense mechanisms. Here, we summarize recent studies revealing these 2 faces of microparticles in cardiovascular disease.

Bacterial alginate production: an overview of its biosynthesis and potential industrial production.

PubMed

Urtuvia, Viviana; Maturana, Nataly; Acevedo, Fernando; Peña, Carlos; Díaz-Barrera, Alvaro

2017-10-07

Alginate is a linear polysaccharide that can be used for different applications in the food and pharmaceutical industries. These polysaccharides have a chemical structure composed of subunits of (1-4)-β-D-mannuronic acid (M) and its C-5 epimer α-L-guluronic acid (G). The monomer composition and molecular weight of alginates are known to have effects on their properties. Currently, these polysaccharides are commercially extracted from seaweed but can also be produced by Azotobacter vinelandii and Pseudomonas spp. as an extracellular polymer. One strategy to produce alginates with different molecular weights and with reproducible physicochemical characteristics is through the manipulation of the culture conditions during fermentation. This mini-review provides a comparative analysis of the metabolic pathways and molecular mechanisms involved in alginate polymerization from A. vinelandii and Pseudomonas spp. Different fermentation strategies used to produce alginates at a bioreactor laboratory scale are described.

Purification and characterization of an alginate lyase from marine Bacterium Vibrio sp. mutant strain 510-64.

PubMed

Hu, Xiaoke; Jiang, Xiaolu; Hwang, Huey-Min

2006-08-01

Marine Vibrio sp. 510 was chosen as a parent strain for screening high producers of alginate lyase using the complex mutagenesis of Ethyl Methanesulphonate and UV radiation treatments. The mutant strain Vibrio sp. 510-64 was selected and its alginate lyase activity was increased by 3.87-fold (reaching 46.12 EU/mg) over that of the parent strain. An extracellular alginate lyase was purified from Vibrio sp. 510-64 cultural supernatant by successive fractionation on DEAE Sepharose FF and two steps of Superdex 75. The purified enzyme yielded a single band on SDS-PAGE with the molecular weight of 34.6 kDa. Data of the N-terminal amino acid sequence indicated that this protein might be a novel alginate lyase. The substrate specificity results demonstrated that the alginate lyase had the specificity for poly G block.

Biodegradable Nanocomposite Films Based on Sodium Alginate and Cellulose Nanofibrils

PubMed Central

Deepa, B.; Abraham, Eldho; Pothan, Laly A.; Cordeiro, Nereida; Faria, Marisa; Thomas, Sabu

2016-01-01

Biodegradable nanocomposite films were prepared by incorporation of cellulose nanofibrils (CNF) into alginate biopolymer using the solution casting method. The effects of CNF content (2.5, 5, 7.5, 10 and 15 wt %) on mechanical, biodegradability and swelling behavior of the nanocomposite films were determined. The results showed that the tensile modulus value of the nanocomposite films increased from 308 to 1403 MPa with increasing CNF content from 0% to 10%; however, it decreased with further increase of the filler content. Incorporation of CNF also significantly reduced the swelling percentage and water solubility of alginate-based films, with the lower values found for 10 wt % in CNF. Biodegradation studies of the films in soil confirmed that the biodegradation time of alginate/CNF films greatly depends on the CNF content. The results evidence that the stronger intermolecular interaction and molecular compatibility between alginate and CNF components was at 10 wt % in CNF alginate films. PMID:28787850

Crystallization and preliminary X-ray analysis of an exotype alginate lyase Atu3025 from Agrobacterium tumefaciens strain C58, a member of polysaccharide lyase family 15

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ochiai, Akihito; Yamasaki, Masayuki; Mikami, Bunzo

2006-05-01

The crystallization and preliminary X-ray characterization of a family PL-15 exotype alginate lyase are presented. Almost all alginate lyases depolymerize alginate in an endolytical fashion via a β-elimination reaction. The alginate lyase Atu3025 from Agrobacterium tumefaciens strain C58, consisting of 776 amino-acid residues, is a novel exotype alginate lyase classified into polysaccharide lyase family 15. The enzyme was crystallized at 293 K by sitting-drop vapour diffusion with polyethylene glycol 4000 as a precipitant. Preliminary X-ray analysis showed that the Atu3025 crystal belonged to space group P2{sub 1} and diffracted to 2.8 Å resolution, with unit-cell parameters a = 107.7, bmore » = 108.3, c = 149.5 Å, β = 91.5°.« less

The study of the structural properties of very low viscosity sodium alginate by small-angle neutron scattering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Badita, C. R., E-mail: ramona@tandem.nipne.ro; University of Bucharest, Faculty of Physics, Atomiştilor 405, CP MG - 11, RO – 077125, Bucharest-Magurele; Aranghel, D., E-mail: daranghe@nipne.ro

2016-03-25

Sodium alginate is a linear polymer extract from brown algae and it is used in the biomedical, food, cosmetics and pharmaceutical industries as solution property modifiers and gelling agents. But despite the extensive studies of the alginate gelation process, still some fundamental questions remain unresolved. The fractal behavior of very low viscosity sodium alginate solutions and their influence on the critical gelation of alginate induced by Ca{sup 2+} ions were investigated using Small-Angle Neutron Scattering (SANS) measurements. SANS data are interpreted using both standard linear plots and the Beaucage model. The scattering intensity is dependent by alginate concentration and Ca{supmore » 2+} concentration. From a critical concentration of 1.0 % w/w our polymer swelled forming spherical structures with rough surfaces. Also the addition of the salt induces the collapse and the appearance of the aggregation and clusters formation.« less

Effects of process variables on the encapsulation of oil in ca-alginate capsules using an inverse gelation technique.

PubMed

Abang, Sariah; Chan, Eng-Seng; Poncelet, Denis

2012-01-01

The objective of this study was to investigate the effects of process variables on the encapsulation of oil in a calcium alginate membrane using an inverse gelation technique. A dispersion of calcium chloride solution in sunflower oil (water-in-oil emulsion) was added dropwise to the alginate solution. The migration of calcium ions to the alginate solution initiates the formation of a ca-alginate membrane around the emulsion droplets. The membrane thickness of wet capsules and the elastic modulus of dry capsules increased following first-order kinetics with an increasing curing time. An increase in the calcium chloride concentration increased the membrane thickness of wet capsules and the elastic modulus of dry capsules. An increase in the alginate concentration decreased the mean diameter of wet capsules but increased the elastic modulus of dry capsules.

The study of the structural properties of very low viscosity sodium alginate by small-angle neutron scattering

NASA Astrophysics Data System (ADS)

Badita, C. R.; Aranghel, D.; Radulescu, A.; Anitas, E. M.

2016-03-01

Sodium alginate is a linear polymer extract from brown algae and it is used in the biomedical, food, cosmetics and pharmaceutical industries as solution property modifiers and gelling agents. But despite the extensive studies of the alginate gelation process, still some fundamental questions remain unresolved. The fractal behavior of very low viscosity sodium alginate solutions and their influence on the critical gelation of alginate induced by Ca2+ ions were investigated using Small-Angle Neutron Scattering (SANS) measurements. SANS data are interpreted using both standard linear plots and the Beaucage model. The scattering intensity is dependent by alginate concentration and Ca2+ concentration. From a critical concentration of 1.0 % w/w our polymer swelled forming spherical structures with rough surfaces. Also the addition of the salt induces the collapse and the appearance of the aggregation and clusters formation.

Preparation and characterization of safe microparticles based on xylan.

PubMed

Cartaxo da Costa Urtiga, Silvana; Aquino Azevedo de Lucena Gabi, Camilla; Rodrigues de Araújo Eleamen, Giovanna; Santos Souza, Bartolomeu; Pessôa, Hilzeth de Luna Freire; Marcelino, Henrique Rodrigues; Afonso de Moura Mendonça, Elisângela; Egito, Eryvaldo Sócrates Tabosa do; Oliveira, Elquio Eleamen

2017-10-01

This work describes the preparation and evaluation of safe xylan-based microparticles prepared by cross-linking polymerization using sodium trimetaphosphate. The resulting microparticles were evaluated for morphology, particle size, polymer-cross-link agent interaction, and in vitro toxicity. The microparticles showed narrow monodisperse size distributions with their mean sizes being between 3.5 and 12.5 µm in dried state. FT-IR analyzes confirmed the interaction between sodium trimetaphosphate and xylan during the cross-linking process with formation of phosphate ester bonds. Additionally, the X-ray diffraction patterns and FT-IR analyzes suggested that little or no cross-linking agent remained inside the microparticles. Furthermore, the in-vitro studies using Artemia salina and human erythrocytes revealed that the microparticles are not toxic. Therefore, the overall results suggest that these xylan microparticles can be used as a platform for new drug delivery system.

Engineering fungal morphology for enhanced production of hydrolytic enzymes by Aspergillus oryzae SBS50 using microparticles.

PubMed

Singh, Bijender

2018-06-01

Effect of microparticles and silver nanoparticles was studied on the production of hydrolytic enzymes by a potent phytase-producing mould, Aspergillus oryzae SBS50. Addition of microparticles, viz. talc powder and aluminum oxide enhanced phytase production from 2894 to 3903 and 2847 to 4204 U/L, cellulase from 2529 to 4931 and 2455 to 3444 U/L, xylanase from 9067 to 9642 and 9994 to 14,783 U/L, amylase from 5880 to 11,000 and 6130 to 13,145 U/L, respectively. Fungal morphology was also engineered by the use of microparticles. Fungal pellet size was significantly reduced (~ 90%) by the addition of microparticles. Fermentation time was reduced from 4 to 3 days after the addition of microparticles, thus increasing the productivity of the enzymes significantly. These results confirmed the importance of microparticles in engineering fungal morphology for enhanced production of hydrolytic enzymes.

The size-reduced Eudragit® RS microparticles prepared by solvent evaporation method - monitoring the effect of selected variables on tested parameters.

PubMed

Vasileiou, Kalliopi; Vysloužil, Jakub; Pavelková, Miroslava; Vysloužil, Jan; Kubová, Kateřina

2018-01-01

Size-reduced microparticles were successfully obtained by solvent evaporation method. Different parameters were applied in each sample and their influence on microparticles was evaluated. As a model drug the insoluble ibuprofen was selected for the encapsulation process with Eudragit® RS. The obtained microparticles were inspected by optical microscopy and scanning electron microscopy. The effect of aqueous phase volume (600, 400, 200 ml) and the concentration of polyvinyl alcohol (PVA; 1.0% and 0.1%) were studied. It was evaluated how those variations and also size can affect microparticle characteristics such as encapsulation efficiency, drug loading, burst effect and microparticle morphology. It was observed that the sample prepared with 600 ml aqueous phase and 1% concentration of polyvinyl alcohol gave the most favorable results.Key words: microparticles solvent evaporation sustained drug release Eudragit RS®.

Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume.

PubMed

Wegman, F; Poldervaart, M T; van der Helm, Y J; Oner, F C; Dhert, W J; Alblas, J

2015-07-27

Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.

Design and evaluation of acrylate polymeric carriers for fabrication of pH-sensitive microparticles.

PubMed

Arya, Amit; Majumdar, Dipak K; Pathak, Dharam Pal; Sharma, Anil K; Ray, Alok R

2017-02-01

Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.4 and -29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer. The microparticles released less than 5% drug at pH 1.2, while more than 90% of the drug load was released at pH 7.4. This suggested the colon targeting nature of the formulations. In experimentally developed colitis in Wistar rats, the microparticle formulation showed significant reduction (p < .05) in the disease activity score (disease symptoms), the colon-to-body weight ratio (tissue edema) and the myeloperoxidase, tumor necrosis factor (TNF)-α and interleukin (IL)-1β activities.

Anti-Neutrophil Cytoplasmic Antibodies Stimulate Release of Neutrophil Microparticles

PubMed Central

Eleftheriou, Despina; Hussain, Abdullah A.K.; Price-Kuehne, Fiona E.; Savage, Caroline O.; Jayne, David; Little, Mark A.; Salama, Alan D.; Klein, Nigel J.; Brogan, Paul A.

2012-01-01

The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3–ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics. PMID:22052057

Optimizing Prednisolone Loading into Distiller's Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery.

PubMed

Lau, Esther T L; Johnson, Stuart K; Williams, Barbara A; Mikkelsen, Deirdre; McCourt, Elizabeth; Stanley, Roger A; Mereddy, Ram; Halley, Peter J; Steadman, Kathryn J

2017-05-19

Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT.

Preparation and evaluation of posaconazole-loaded enteric microparticles in rats.

PubMed

Yang, Min; Dong, Zhonghua; Zhang, Yongchun; Zhang, Fang; Wang, Yongjie; Zhao, Zhongxi

2017-04-01

Posaconazole (POS) is an antifungal compound which has a low oral bioavailability. The aim of this study was to prepare POS enteric microparticles to enhance its oral bioavailability. POS enteric microparticles were prepared with hypromellose acetate succinate (HPMCAS) via the spray drying method. The solvent mixtures of acetone and ethanol used in the preparation of the microparticles were optimized to produce the ideal POS enteric microparticles. Multivariate data analysis using a principal component analysis (PCA) was used to find the relationship among the HPMCAS molecular characteristics, particle properties and drug release kinetics from the spray dried microparticles. The optimal spray solvent mixtures were critical to produce the POS microparticles with the defined polymer entanglement index, drug surface enrichment, particle size and drug loading. The HPMCAS molecular characteristics affected the microscopic connectivity and diffusivity of polymer matrix and eventually influenced the drug release behavior, and enhanced the bioavailability of POS. These studies suggested that the selection of suitable solvent mixtures of acetone and ethanol used in the spray drying of the microparticles was quite important to produce the entangled polymer structures with preferred polymer molecular properties of polymer coiling, overlap concentration and entanglement index. Additional studies on particle size and surface drug enrichment eventually produced HPMCAS-based enteric microparticles to enhance the oral bioavailability of POS.

Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery

PubMed Central

Giri, Tapan Kumar; Choudhary, Chhatrapal; Ajazuddin; Alexander, Amit; Badwaik, Hemant; Tripathi, Dulal Krishna

2012-01-01

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active. PMID:23960828

Preparation of protein loaded poly(D,L-lactide-co-glycolide) microparticles for the antigen delivery to dendritic cells using a static micromixer.

PubMed

Wischke, Christian; Lorenzen, Dirk; Zimmermann, Julian; Borchert, Hans-Hubert

2006-04-01

The cellular immune response against tumors, viruses, or intracellular bacteria requires adequate antigen delivery to professional phagocytes, their processing and the presentation of antigenic peptides to T-cells. Biodegradable microparticles to enhance antigen phagocytosis and the response of cytotoxic lymphocytes have been proposed. The aim of the present study was to formulate poly(lactide-co-glycolide) (PLGA) microparticles using a w/o/w solvent evaporation procedure in order to obtain suitable vehicles for vaccination. Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as a model antigen. For microparticle preparation a static micromixer was employed. Microparticles of 2-3 microm can be produced with good reproducibility by applying high flow rates at the micromixer. Microparticles with a smooth surface and only one pore were observed using scanning electron microscopy (SEM). Confocal laser scanning microscopy (CLSM) allowed localisation of the FITC-BSA near the surface of the microparticle. Microencapsulation of FITC-BSA did not altered the polymer characteristics, as determined by measuring the glass transition temperature. Additionally we could determine residual methylene chloride, employed as solvent in microparticle preparation, to be less than 1/1000 of the USP and Ph. Eur. limit. The microparticles described herein were able to deliver the model antigen to human dendritic cells (DC).

Facile and High-Throughput Synthesis of Functional Microparticles with Quick Response Codes.

PubMed

Ramirez, Lisa Marie S; He, Muhan; Mailloux, Shay; George, Justin; Wang, Jun

2016-06-01

Encoded microparticles are high demand in multiplexed assays and labeling. However, the current methods for the synthesis and coding of microparticles either lack robustness and reliability, or possess limited coding capacity. Here, a massive coding of dissociated elements (MiCODE) technology based on innovation of a chemically reactive off-stoichimetry thiol-allyl photocurable polymer and standard lithography to produce a large number of quick response (QR) code microparticles is introduced. The coding process is performed by photobleaching the QR code patterns on microparticles when fluorophores are incorporated into the prepolymer formulation. The fabricated encoded microparticles can be released from a substrate without changing their features. Excess thiol functionality on the microparticle surface allows for grafting of amine groups and further DNA probes. A multiplexed assay is demonstrated using the DNA-grafted QR code microparticles. The MiCODE technology is further characterized by showing the incorporation of BODIPY-maleimide (BDP-M) and Nile Red fluorophores for coding and the use of microcontact printing for immobilizing DNA probes on microparticle surfaces. This versatile technology leverages mature lithography facilities for fabrication and thus is amenable to scale-up in the future, with potential applications in bioassays and in labeling consumer products. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spray Dried Chitosan Microparticles for Intravesical Delivery of Celecoxib: Preparation and Characterization.

PubMed

Lopedota, Angela; Cutrignelli, Annalisa; Laquintana, Valentino; Denora, Nunzio; Iacobazzi, Rosa Maria; Perrone, Mara; Fanizza, Elisabetta; Mastrodonato, Maria; Mentino, Donatella; Lopalco, Antonio; Depalo, Nicoletta; Franco, Massimo

2016-09-01

Chitosan microparticles containing celecoxib (CB), were developed as chemoprevention of bladder cancer. Furthermore two inclusion complexes of CB with methyl-β-cyclodextrin (C1 and C2) were prepared to improve the solubility of the drug. C1 and C2 were obtained by freeze-drying and characterized in the solid state and in solution. Microparticles loaded with CB or C1 or C2 were prepared by spray drying and fully characterized. The yield and encapsulation efficiencies of microparticles depended by both the viscosity and the presence of the inclusion complex in the feed medium nebulised. Generally, the microparticles exhibited a spherical shape with mean diameter of approximately 2 μm which was compatible with local intravesical administration using a catheter. The CB release studies from the microparticles allowed us to identify both immediate release systems (microparticles including the complexes) and prolonged release systems (microparticles including CB alone). The latter exhibited good adhesion to the bladder mucosa, as highlighted by a mucoadhesion study. Histological studies revealed a desquamation of the superficial cells when the bladder mucosa was treated with microparticles loaded with CB, while the morphology of the urothelium did not change when it was treated with microparticles loaded with the inclusion complex. A new CB intravesical formulation than can easily be administered with a catheter and is able to release the drug at the target site for several hours was realized. This new delivery system could be a good alternative to classic oral CB administration.

IGF-1 Release Kinetics from Chitosan Microparticles Fabricated Using Environmentally Benign Conditions

PubMed Central

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2014-01-01

The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated into microparticles to study release kinetics and bioactivity. In order to authenticate the harms of using organic solvents like hexane and acetone during microparticle preparation, IGF-1 encapsulated microparticles prepared by the emulsification and coacervation methods were compared. The microparticles fabricated by emulsification method have shown a significant decrease (p<0.05) in IGF-1 encapsulation efficiency, and cumulative release during the two-week period. The biocompatibility of chitosan microparticles and the bioactivity of the released IGF-1 were determined in vitro by live/dead viability assay. The mineralization data observed with Von Kossa assay, was supported by mRNA expression levels of osterix and runx2, which are transcription factors necessary for osteoblasts differentiation. Real time RT-PCR data showed an increased expression of runx 2 and a decreased expression of osterix over time, indicating differentiating osteoblasts. Chitosan microparticles prepared in optimum environmental conditions are a promising controlled delivery system for cells to attach, proliferate, differentiate and mineralize, thereby acting as a suitable bone repairing material. PMID:25063148

Fabrication of Protein Microparticles and Microcapsules with Biomolecular Tools

NASA Astrophysics Data System (ADS)

Cheung, Kwan Yee; Lai, Kwok Kei; Mak, Wing Cheung

2018-05-01

Microparticles have attracted much attention for medical, analytical and biological applications. Calcium carbonate (CaCO3) templating method with the advantages of having narrow size distribution, controlled morphology and good biocompatibility that has been widely used for the synthesis of various protein-based microparticles. Despite CaCO3 template is biocompatible, most of the conventional methods to create stable protein microparticles are mainly driven by chemical crosslink reagents which may induce potential harmful effect and remains undesirable especially for biomedical or clinical applications. In this article, we demonstrate the fabrication of protein microparticles and microcapsules with an innovative method using biomolecular tools such as enzymes and affinity molecules to trigger the assembling of protein molecules within a porous CaCO3 template followed by a template removal step. We demonstrated the enzyme-assisted fabrication of collagen microparticles triggered by transglutaminase, as well as the affinity-assisted fabrication of BSA-biotin avidin microcapsules triggered by biotin-avidin affinity interaction, respectively. Based on the different protein assemble mechanisms, the collagen microparticles appeared as a solid-structured particles, while the BSA-biotin avidin microcapsules appeared as hollow-structured morphology. The fabrication procedures are simple and robust that allows producing protein microparticles or microcapsules under mild conditions at physiological pH and temperature. In addition, the microparticle morphologies, protein compositions and the assemble mechanisms were studied. Our technology provides a facile approach to design and fabricate protein microparticles and microcapsules that are useful in the area of biomaterials, pharmaceuticals and analytical chemistry.

Controlled release of beta-estradiol from PLAGA microparticles: the effect of organic phase solvent on encapsulation and release.

PubMed

Birnbaum, D T; Kosmala, J D; Henthorn, D B; Brannon-Peppas, L

2000-04-03

To determine the effect of the organic solvent used during microparticle preparation on the in vitro release of beta-estradiol, a number of formulations were evaluated in terms of size, shape and drug delivery performance. Biodegradable microparticles of poly(lactide-co-glycolide) were prepared containing beta-estradiol that utilized dichloromethane, ethyl acetate or a mixture of dichloromethane and methanol as the organic phase solvent during the particle preparation. The drug delivery behavior from the microparticles was studied and comparisons were made of their physical properties for different formulations. The varying solubilities of beta-estradiol and poly(lactide-co-glycolide) in the solvents studied resulted in biodegradable microparticles with very different physical characteristics. Microparticles prepared from solid suspensions of beta-estradiol using dichloromethane as the organic phase solvent were similar in appearance to microparticles prepared without drug. Microparticles prepared from dichloromethane/methanol solutions appeared transparent to translucent depending on the initial amount of drug used in the formulation. Microparticles prepared using ethyl acetate appeared to have the most homogeneous encapsulation of beta-estradiol, appearing as solid white spheres regardless of initial drug content. Studies showed that microparticles prepared from either ethyl acetate or a mixture of dichloromethane and methanol gave a more constant release profile of beta-estradiol than particles prepared using dichloromethane alone. For all formulations, an initial burst of release increased with increasing drug loading, regardless of the organic solvent used.

Antibacterial Loaded Spray Dried Chitosan Polyelectrolyte Complexes as Dry Powder Aerosol for the Treatment of Lung Infections

PubMed Central

Mishra, Brahmeshwar; Mishra, Madhusmita; Yadav, Sarita Kumari

2017-01-01

Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections. Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr’s index, solid state interaction by XRD, aerosolization behaviour and in-vitro drug release. In-vitro cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis. The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher Cmax values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution. The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection. PMID:28496463

Copper(II)-mediated thermolysis of alginates: a model kinetic study on the influence of metal ions in the thermochemical processing of macroalgae

PubMed Central

Rowbotham, J. S.; Dyer, P. W.; Greenwell, H. C.; Selby, D.; Theodorou, M. K.

2013-01-01

Thermochemical processing methods such as pyrolysis are of growing interest as a means of converting biomass into fuels and commodity chemicals in a sustainable manner. Macroalgae, or seaweed, represent a novel class of feedstock for pyrolysis that, owing to the nature of the environments in which they grow coupled with their biochemistry, naturally possess high metal contents. Although the impact of metals upon the pyrolysis of terrestrial biomass is well documented, their influence on the thermochemical conversion of marine-derived feeds is largely unknown. Furthermore, these effects are inherently difficult to study, owing to the heterogeneous character of natural seaweed samples. The work described in this paper uses copper(II) alginate, together with alginic acid and sodium alginate as model compounds for exploring the effects of metals upon macroalgae thermolysis. A thermogravimetric analysis–Fourier transform infrared spectroscopic study revealed that, unusually, Cu2+ ions promote the onset of pyrolysis in the alginate polymer, with copper(II) alginate initiating rapid devolatilization at 143°C, 14°C lower than alginic acid and 61°C below the equivalent point for sodium alginate. Moreover, this effect was mirrored in a sample of wild Laminaria digitata that had been doped with Cu2+ ions prior to pyrolysis, thus validating the use of alginates as model compounds with which to study the thermolysis of macroalgae. These observations indicate the varying impact of different metal species on thermochemical behaviour of seaweeds and offer an insight into the pyrolysis of brown macroalgae used in phytoremediation of metal-containing waste streams. PMID:24427515

Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles.

PubMed

Venkatesan, Jayachandran; Lee, Jin-Young; Kang, Dong Seop; Anil, Sukumaran; Kim, Se-Kwon; Shim, Min Suk; Kim, Dong Gyu

2017-05-01

The main aim of this study was to obtain porous antimicrobial composites consisting of chitosan, alginate, and biosynthesized silver nanoparticles (AgNPs). Chitosan and alginate were used owing to their pore-forming capacity, while AgNPs were used for their antimicrobial property. The developed porous composites of chitosan-alginate-AgNPs were characterized using Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy, X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM). The FT-IR results revealed the presence of a strong chemical interaction between chitosan and alginate due to polyelectrolyte complex; whereas, the XRD results confirmed the presence of AgNPs in the composites. The dispersion of AgNPs in the porous membrane was uniform with a pore size of 50-500μm. Antimicrobial activity of the composites was checked with Escherichia coli and Staphylococcus aureus. The developed composites resulted in the formation of a zone of inhibition of 11±1mm for the Escherichia coli, and 10±1mm for Staphylococcus aureus. The bacterial filtration efficiency of chitosan-alginate-AgNPs was 1.5-times higher than that of the chitosan-alginate composite. The breast cancer cell line MDA-MB-231 was used to test the anticancer activity of the composites. The IC 50 value of chitosan-alginate-AgNPs on MDA-MB-231 was 4.6mg. The developed chitosan-alginate-AgNPs composite showed a huge potential for its applications in antimicrobial filtration and cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamics of rigid microparticles at the interface of co-flowing immiscible liquids in a microchannel.

PubMed

Jayaprakash, K S; Banerjee, U; Sen, A K

2017-05-01

We report the dynamical migration behavior of rigid polystyrene microparticles at an interface of co-flowing streams of primary CP 1 (aqueous) and secondary CP 2 (oils) immiscible phases at low Reynolds numbers (Re) in a microchannel. The microparticles initially suspended in the CP 1 either continue to flow in the bulk CP 1 or migrate across the interface into CP 2 , when the stream width of the CP 1 approaches the diameter of the microparticles. Experiments were performed with different secondary phases and it is found that the migration criterion depends on the sign of the spreading parameter S and the presence of surfactant at the interface. To substantiate the migration criterion, experiments were also carried out by suspending the microparticles in CP 2 (oil phase). Our study reveals that in case of aqueous-silicone oil combination, the microparticles get attached to the interface since S<0 and the three phase contact angle, θ>90°. For complete detachment of microparticles from the interface into the secondary phase, additional energy ΔG is needed. We discuss the role of interfacial perturbation, which causes detachment of microparticles from the interface. In case of mineral and olive oils, the surfactants present at the interface prevents attachment of the microparticles to the interface due to the repulsive disjoining pressure. Finally, using a aqueous-silicone oil system, we demonstrate size based sorting of microparticles of size 25μm and 15μm respectively from that of 15μm and 10μm and study the variation of separation efficiency η with the ratio of the width of the aqueous stream to the diameter of the microparticles ρ. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative studies on the properties of glycyrrhetinic acid-loaded PLGA microparticles prepared by emulsion and template methods.

PubMed

Wang, Hong; Zhang, Guangxing; Sui, Hong; Liu, Yanhua; Park, Kinam; Wang, Wenping

2015-12-30

The O/W emulsion method has been widely used for the production of poly (lactide-co-glycolide) (PLGA) microparticles. Recently, a template method has been used to make homogeneous microparticles with predefined size and shape, and shown to be useful in encapsulating different types of active compounds. However, differences between the template method and emulsion method have not been examined. In the current study, PLGA microparticles were prepared by the two methods using glycyrrhetinic acid (GA) as a model drug. The properties of obtained microparticles were characterized and compared on drug distribution, in vitro release, and degradation. An encapsulation efficiency of over 70% and a mean particle size of about 40μm were found for both methods. DSC thermograms and XRPD diffractograms indicated that GA was highly dispersed or in the amorphous state in the matrix of microparticles. The emulsion method produced microparticles of a broad size distribution with a core-shell type structure and many drug-rich domains inside each microparticle. Its drug release and matrix degradation was slow before Day 50 and then accelerated. In contrast, the template method formed microparticles with narrow size distribution and drug distribution without apparent drug-rich domains. The template microparticles with a loading efficiency of 85% exhibited a zero-order release profile for 3 months after the initial burst release of 26.7%, and a steady surface erosion process as well. The same microparticles made by two different methods showed two distinguished drug release profiles. The two different methods can be supplementary with each other in optimization of drug formulation for achieving predetermined drug release patterns. Copyright © 2015 Elsevier B.V. All rights reserved.

Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

PubMed

Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Phospholipid Binding Protein C Inhibitor (PCI) Is Present on Microparticles Generated In Vitro and In Vivo

PubMed Central

Einfinger, Katrin; Badrnya, Sigrun; Furtmüller, Margareta; Handschuh, Daniela; Lindner, Herbert; Geiger, Margarethe

2015-01-01

Protein C inhibitor is a secreted, non-specific serine protease inhibitor with broad protease reactivity. It binds glycosaminoglycans and anionic phospholipids, which can modulate its activity. Anionic phospholipids, such as phosphatidylserine are normally localized to the inner leaflet of the plasma membrane, but are exposed on activated and apoptotic cells and on plasma membrane-derived microparticles. In this report we show by flow cytometry that microparticles derived from cultured cells and activated platelets incorporated protein C inhibitor during membrane blebbing. Moreover, protein C inhibitor is present in/on microparticles circulating in normal human plasma as judged from Western blots, ELISAs, flow cytometry, and mass spectrometry. These plasma microparticles are mainly derived from megakaryocytes. They seem to be saturated with protein C inhibitor, since they do not bind added fluorescence-labeled protein C inhibitor. Heparin partially removed microparticle-bound protein C inhibitor, supporting our assumption that protein C inhibitor is bound via phospholipids. To assess the biological role of microparticle-bound protein C inhibitor we performed protease inhibition assays and co-precipitated putative binding partners on microparticles with anti-protein C inhibitor IgG. As judged from amidolytic assays microparticle-bound protein C inhibitor did not inhibit activated protein C or thrombin, nor did microparticles modulate the activity of exogenous protein C inhibitor. Among the proteins co-precipitating with protein C inhibitor, complement factors, especially complement factor 3, were most striking. Taken together, our data do not support a major role of microparticle-associated protein C inhibitor in coagulation, but rather suggest an interaction with proteins of the complement system present on these phospholipid vesicles. PMID:26580551

Assessing consumption of bioactive micro-particles by filter-feeding Asian carp

USGS Publications Warehouse

Jensen, Nathan R.; Amberg, Jon J.; Luoma, James A.; Walleser, Liza R.; Gaikowski, Mark P.

2012-01-01

Silver carp Hypophthalmichthys molitrix (SVC) and bighead carp H. nobilis (BHC) have impacted waters in the US since their escape. Current chemical controls for aquatic nuisance species are non-selective. Development of a bioactive micro-particle that exploits filter-feeding habits of SVC or BHC could result in a new control tool. It is not fully understood if SVC or BHC will consume bioactive micro-particles. Two discrete trials were performed to: 1) evaluate if SVC and BHC consume the candidate micro-particle formulation; 2) determine what size they consume; 3) establish methods to evaluate consumption of filter-feeders for future experiments. Both SVC and BHC were exposed to small (50-100 μm) and large (150-200 μm) micro-particles in two 24-h trials. Particles in water were counted electronically and manually (microscopy). Particles on gill rakers were counted manually and intestinal tracts inspected for the presence of micro-particles. In Trial 1, both manual and electronic count data confirmed reductions of both size particles; SVC appeared to remove more small particles than large; more BHC consumed particles; SVC had fewer overall particles in their gill rakers than BHC. In Trial 2, electronic counts confirmed reductions of both size particles; both SVC and BHC consumed particles, yet more SVC consumed micro-particles compared to BHC. Of the fish that ate micro-particles, SVC consumed more than BHC. It is recommended to use multiple metrics to assess consumption of candidate micro-particles by filter-feeders when attempting to distinguish differential particle consumption. This study has implications for developing micro-particles for species-specific delivery of bioactive controls to help fisheries, provides some methods for further experiments with bioactive micro-particles, and may also have applications in aquaculture.

Detection of microparticles from human red blood cells by multiparametric flow cytometry

PubMed Central

Grisendi, Giulia; Finetti, Elena; Manganaro, Daniele; Cordova, Nicoletta; Montagnani, Giuliano; Spano, Carlotta; Prapa, Malvina; Guarneri, Valentina; Otsuru, Satoru; Horwitz, Edwin M.; Mari, Giorgio; Dominici, Massimo

2015-01-01

Background During storage, red blood cells (RBC) undergo chemical and biochemical changes referred to as “storage lesions”. These events determine the loss of RBC integrity, resulting in lysis and release of microparticles. There is growing evidence of the clinical importance of microparticles and their role in blood transfusion-related side effects and pathogen transmission. Flow cytometry is currently one of the most common techniques used to quantify and characterise microparticles. Here we propose multiparametric staining to monitor and quantify the dynamic release of microparticles by stored human RBC. Material and methods RBC units (n=10) were stored under blood bank conditions for up to 42 days. Samples were tested at different time points to detect microparticles and determine the haemolysis rate (HR%). Microparticles were identified by flow cytometry combining carboxyfluorescein diacetate succinimidyl ester (CFSE) dye, annexin V and anti-glycophorin A antibody. Results We demonstrated that CFSE can be successfully used to label closed vesicles with an intact membrane. The combination of CFSE and glycophorin A antibody was effective for monitoring and quantifying the dynamic release of microparticles from RBC during storage. Double staining with CFSE/glycophorin A was a more precise approach, increasing vesicle detection up to 4.7-fold vs the use of glycophorin A/annexin V alone. Moreover, at all the time points tested, we found a robust correlation (R=0.625; p=0.0001) between HR% and number of microparticles detected. Discussion Multiparametric staining, based on a combination of CFSE, glycophorin A antibody and annexin V, was able to detect, characterise and monitor the release of microparticles from RBC units during storage, providing a sensitive approach to labelling and identifying microparticles for transfusion medicine and, more broadly, for cell-based therapies. PMID:25369588

Increased serum concentration of immune cell derived microparticles in polymyositis/dermatomyositis.

PubMed

Baka, Zsuzsanna; Senolt, Ladislav; Vencovsky, Jiri; Mann, Herman; Simon, Piroska Sebestyén; Kittel, Agnes; Buzás, Edit; Nagy, György

2010-02-16

Microparticles are recently recognized players of intercellular communication. They are involved in signal transduction, cell activation and apoptosis. Their importance is also suggested in autoimmune diseases such as rheumatoid arthritis and systemic sclerosis. We investigated the role of microparticles in polymyositis/dermatomyositis, a group of rare autoimmune diseases, characterized by specific skin lesions and muscle weakness. The plasma concentration of monocyte and lymphocyte derived microparticles of 20 patients with polymyositis/dermatomyositis and 20 healthy controls were determined by flow cytometry. The structure of microparticles was visualized by electron microscopy. Significantly elevated numbers of monocyte (CD14 positive), T-lymphocyte (CD3 positive) and B-lymphocyte (CD19 positive) derived microparticles were found in the plasma samples of polymyositis/dermatomyositis patients, compared to healthy controls (p=0.001, 0.01 and 0.006, respectively). Furthermore, the plasma levels of monocyte and B-lymphocyte derived microparticles correlated with the manual muscle strength test (r=0.497, p=0.027; r=0.508, p=0.023; respectively). Patients with anti-Jo-1 antibody and lung involvement had significantly higher numbers of T- and B-lymphocyte and monocyte derived MPs (p=0.006, 0.012 and 0.007, respectively, for anti-Jo-1; p=0.013, 0.016 and 0.025, respectively, for lung involvement). After ultracentrifugation, CK activity could be detected only in traces in the resuspended pellet containing microparticles of healthy and diseased individuals. The electron microscopy revealed slightly different microparticles in the samples of patients with polymyositis/dermatomyositis. These results suggest that immune cell derived microparticles may contribute to the inflammatory process in polymyositis/dermatomyositis, however, CK-positive, possibly muscle derived microparticles do not seem to be present in the blood of patients with polymyositis/dermatomyositis. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Complement activation on the surface of cell-derived microparticles during cardiac surgery with cardiopulmonary bypass - is retransfusion of pericardial blood harmful?

PubMed

Biró, E; van den Goor, J M; de Mol, B A; Schaap, M C; Ko, L-Y; Sturk, A; Hack, C E; Nieuwland, R

2011-01-01

To investigate whether cell-derived microparticles play a role in complement activation in pericardial blood of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and whether microparticles in pericardial blood contribute to systemic complement activation upon retransfusion. Pericardial blood of 13 patients was retransfused in 9 and discarded in 4 cases. Microparticles were isolated from systemic blood collected before anesthesia (T1) and at the end of CPB (T2), and from pericardial blood. The microparticles were analyzed by flow cytometry for bound complement components C1q, C4 and C3, and bound complement activator molecules C-reactive protein (CRP), serum amyloid P-component (SAP), immunoglobulin (Ig)M and IgG. Fluid-phase complement activation products (C4b/c, C3b/c) and activator molecules were determined by ELISA. Compared with systemic T1 blood, pericardial blood contained increased C4b/c and C3b/c, and increased levels of microparticles with bound complement components. In systemic T1 samples, microparticle-bound CRP, whereas in pericardial blood, microparticle-bound SAP and IgM were associated with complement activation. At the end of CPB, increased C3b/c (but not C4b/c) was present in systemic T2 blood compared with T1, while concentrations of microparticles binding complement components and of those binding complement activator molecules were similar. Concentrations of fluid-phase complement activation products and microparticles were similar in patients whether or not retransfused with pericardial blood. In pericardial blood of patients undergoing cardiac surgery with CPB, microparticles contribute to activation of the complement system via bound SAP and IgM. Retransfusion of pericardial blood, however, does not contribute to systemic complement activation.

Cell-derived microparticles and complement activation in preeclampsia versus normal pregnancy.

PubMed

Biró, E; Lok, C A R; Hack, C E; van der Post, J A M; Schaap, M C L; Sturk, A; Nieuwland, R

2007-01-01

Inflammation plays a major role in the vascular dysfunction seen in preeclampsia, and several studies suggest involvement of the complement system. To investigate whether complement activation on the surface of microparticles is increased in plasma of preeclamptic patients versus healthy pregnant controls. Microparticles from plasma of preeclamptic (n=10), healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed by flow cytometry for bound complement components (C1q, C4, C3) and complement activator molecules (C-reactive protein [CRP], serum amyloid P component [SAP], immunoglobulin [Ig]M, IgG). Fluid phase complement activation products and activator molecules were also determined. Levels of microparticles with bound complement components showed no increase in complement activation on the microparticle surface in preeclamptic women, in line with levels of fluid phase complement activation products. In healthy nonpregnant and pregnant women, bound CRP was associated with classical pathway activation on the microparticle surface, and in healthy pregnant women IgM and IgG molecules also contributed. In preeclamptic women, microparticles with bound SAP and those with IgG seemed to contribute to C1q binding without a clear association to further classical pathway activation. Furthermore, significantly increased levels of microparticles with bound CRP were present in preeclamptic compared with healthy pregnant women (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases in complement activation. We found no evidence of increased complement activation on the microparticle surface in preeclamptic women. Microparticles with bound CRP were significantly increased, but in contrast to healthy pregnant and nonpregnant women, this was not associated with increased classical pathway activation on the surface of the microparticles.

Galectin-3 binding protein links circulating microparticles with electron dense glomerular deposits in lupus nephritis.

PubMed

Nielsen, C T; Østergaard, O; Rekvig, O P; Sturfelt, G; Jacobsen, S; Heegaard, N H H

2015-10-01

A high level of galectin-3-binding protein (G3BP) appears to distinguish circulating cell-derived microparticles in systemic lupus erythematosus (SLE). The aim of this study is to characterize the population of G3BP-positive microparticles from SLE patients compared to healthy controls, explore putative clinical correlates, and examine if G3BP is present in immune complex deposits in kidney biopsies from patients with lupus nephritis. Numbers of annexin V-binding and G3BP-exposing plasma microparticles from 56 SLE patients and 36 healthy controls were determined by flow cytometry. Quantitation of microparticle-associated G3BP, C1q and immunoglobulins was obtained by liquid chromatography tandem mass spectrometry (LC-MS/MS). Correlations between microparticle-G3BP data and clinical parameters were analyzed. Co-localization of G3BP with in vivo-bound IgG was examined in kidney biopsies from one non-SLE control and from patients with class IV (n = 2) and class V (n = 1) lupus nephritis using co-localization immune electron microscopy. Microparticle-G3BP, microparticle-C1q and microparticle-immunoglobulins were significantly (P < 0.01) increased in SLE patients by LC-MS/MS. Three G3BP-exposing microparticle populations could be discerned by flow cytometry, including two subpopulations that were significantly increased in SLE samples (P = 0.01 and P = 0.0002, respectively). No associations of G3BP-positive microparticles with clinical manifestations or disease activity were found. Immune electron microscopy showed co-localization of G3BP with in vivo-bound IgG in glomerular electron dense immune complex deposits in all lupus nephritis biopsies. Both circulating microparticle-G3BP numbers as well as G3BP expression are increased in SLE patients corroborating G3BP being a feature of SLE microparticles. By demonstrating G3BP co-localized with deposited immune complexes in lupus nephritis, the study supports cell-derived microparticles as a major autoantigen source and provides a new understanding of the origin of immune complexes occurring in lupus nephritis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Preparation and Characterization of Doripenem-Loaded Microparticles for Pulmonary Delivery.

PubMed

Yildiz-Peköz, Ayca; Akbal, Ozlem; Tekarslan, S Hande; Sagirli, A Olcay; Mulazimoglu, Lütfiye; Morina, Deniz; Cevher, Erdal

2018-06-07

Pneumonia is a bacterial lower respiratory tract infection that has a high morbidity rate. The gram-negative pathogen Pseudomonas aeruginosa is a significant cause of nosocomial infections and ventilator-associated pneumonias and is mainly treated by carbapenems. Doripenem is a carbapenem drug, which has a broad-spectrum antibacterial activity. The aim of this study was to develop doripenem-loaded chitosan microparticles for pulmonary administration to provide more efficient treatment for pneumonia. Ionotropic gelation and the spray-drying method were used to obtain doripenem-loaded chitosan microparticles with different lactose, trehalose, and L-leucine concentrations. Physicochemical characteristics, in vitro drug release properties, and aerodynamics properties were investigated and in vitro antimicrobial susceptibility tests of the formulations were performed. Assessment of aerodynamic properties of the powders, including Mass Median Aerodynamic Diameter, size distribution, and fine particle fraction (FPF), were performed using a Next Generation Impactor. Cytotoxicity of the fabricated microparticles was assessed using the Calu-3 cell airway epithelial cell line. Optimum microparticles were produced using a combination of ionotropic gelation and spray-drying methods. Spray-dried microparticle production yield was relatively high (74.03% ± 3.88% to 98.23% ± 1.70%). Lactose, trehalose, and L-leucine were added to the formulation to prevent aggregation produced by the ionotropic gelation spray-drying method. Each formulation's encapsulation efficiency was above 78.98% ± 2.37%. The doripenem-loaded microparticle mean diameter ranged from 3.8 ± 0.110 to 6.9 ± 0.090 μm. Microparticles with 20% (w/w) L-leucine had the highest FPF ratio indicating the best aerosolization properties of the formulations. The efficacy of the formulations as an antibacterial agent was increased by forming doripenem-loaded microparticles compared to blank microparticles. P. aeruginosa showed the same susceptibility to all doripenem-loaded microparticle formulations. Cell viability of microparticles was between 70% ± 0.08% and 90% ± 0.04% at 0.5 and 10 mg/mL concentration, respectively. Doripenem-loaded microparticles, produced using a combination of ionotropic gelation and spray-drying methods, are suitable for pulmonary drug delivery based on their particles size, zeta potential, cytotoxicity and high production yield. To our knowledge, this is the first study that microparticles containing doripenem were produced and characterized.

Physicochemical characterization and biocompatibility of alginate-polycation microcapsules designed for islet transplantation

NASA Astrophysics Data System (ADS)

Tam, Susan Kimberly

Microencapsulation represents a method for immunoprotecting transplanted therapeutic cells or tissues from graft rejection using a physical barrier. This approach is advantageous in that it eliminates the need to induce long-term immunosuppression and allows the option of transplanting non-cadaveric cell sources, such as animal cells and stem cell-derived tissues. The microcapsules that we have investigated are designed to immunoprotect islets of Langerhans (i.e. clusters of insulin-secreting cells), with the goal of treating insulin-dependent diabetes. With the aid of techniques for physicochemical analysis, this research focused on understanding which properties of the microcapsule are the most important for determining its biocompatibility. The objective of this work was to elucidate correlations between the chemical make-up, physicochemical properties, and in vivo biocompatibility of alginate-based microcapsules. Our approach was based on the hypothesis that the immune response to the microcapsules is governed by, and can therefore be controlled by, specific physicochemical properties of the microcapsule and its material components. The experimental work was divided into five phases, each associated with a specific aim : (1) To prove that immunoglobulins adsorb to the surface of alginate-polycation microcapsules, and to correlate this adsorption with the microcapsule chemistry. (2) To test interlaboratory reproducibility in making biocompatible microcapsules, and evaluate the suitability of our materials and fabrication protocols for subsequent studies. (3) To determine which physicochemical properties of alginates affect the in vivo biocompatibility of their gels. (4) To determine which physiochemical properties of alginate-polycation microcapsules are most important for determining their in vivo biocompatibility (5) To determine whether a modestly immunogenic membrane hinders or helps the ability of the microcapsule to immunoprotect islet xenografts in diabetic mice. To achieve these aims, extensive physicochemical analyses of the alginates and microcapsules were carried out. Among the properties of the alginates that were investigated include their purity (LAL assay, microBCA), chemical composition (nuclear magnetic resonance, NMR), elemental composition (x-ray photoelectron spectroscopy, XPS), and hydrophilicity (contact angle technique). As for the microcapsules, we also examined their surface chemical composition (XPS), hydrophilicity, as well as alginate-polycation interactions (Fourier transform infrared spectroscopy, FTIR), and membrane strength (osmotic swelling). The results of this research led to a number of important conclusions about the biocompatibility of alginates and alginate-based microcapsules. First of all, purifying an alginate does not guarantee its biocompatibility. Indeed, we provided evidence that both the alginate chemical composition (i.e. relative content of mannuronate and guluronate) and its intrinsic viscosity influence the extent of host cell adhesion to alginate gel beads. Using a biocompatible alginate, we then provided evidence that microcapsule biocompatibility is greatly compromised by its polycationic membrane. We showed that this membrane is responsible for the adsorption of opsonizing proteins in vitro and the adhesion of immune cells in vivo. That said, the severity of inflammatory response to the membrane can vary, and this depended on the microcapsule design, including the choice of alginate and polycation type. Results of our physicochemical analyses suggested that the most important factor determining biocompatibility is the ability of the polycation to diffuse into, and subsequently bind to, the alginate gel core. Moreover, adding a final coating of alginate had no significant effect on reversing the effects of the membrane on various microcapsule properties (surface composition, hydrophobicity, stability), nor did this coating reduce its immunogenicity. Although we repeatedly provided evidence that the microcapsule membrane is the main problem for biocompatibility, we also demonstrated that the severity of this problem can vary according to the fabrication details. This is an important note, as it confirms the possibility of achieving optimal microcapsule biocompatibility if the interactions between the alginate and polycation are ideal. (Abstract shortened by UMI.)

Alginate Particles with Ovalbumin (OVA) Peptide Can Serve as a Carrier and Adjuvant for Immune Therapy in B16-OVA Cancer Model.

PubMed

Zhu, Longbao; Ge, Fei; Yang, Liangjun; Li, Wanzhen; Wei, Shenghua; Tao, Yugui; Du, Guocheng

2017-04-28

BACKGROUND Alginate is a natural polysaccharide obtained from brown algae and has been shown to have numerous applications in biomedical science, such as wound healing, delivery of bioactive agents, and cell transplantation. Ovalbumin (OVA) peptide 323-339 has been reported to be involved in immune response.  MATERIAL AND METHODS This work investigated the use of alginate particles as a carrier and adjuvant for the immune therapy of cancer. Alginate particles loaded with OVA peptide were produced via emulsion. A tumor model was established in C57BL/6J mice via subcutaneous injection of 3×105 B16-OVA tumor cells. The effect of alginate/OVA peptide on cell viability was analyzed by use of the CCK-8 assay kit. Activation of macrophages was examined by checking cell surface makers CD40 and CD86 by FACs. RESULTS Alginate/OVA peptide inhibited tumor progression more effectively than using the peptide alone. The viability and uptake study illustrated that this particle is safe and non-toxic. The activation study demonstrated that alginate particles can promote the activation of surface markers on macrophages. ELISA assay showed that the particles with peptide can promote the secretion of inflammatory and effector cytokines from macrophages.  CONCLUSIONS This study demonstrated that alginate has dual functions in immune therapy of cancer, serving both as a carrier and an adjuvant.

The relationship between digital model accuracy and time-dependent deformation of alginate impressions.

PubMed

Alcan, Toros; Ceylanoğlu, Cenk; Baysal, Bekir

2009-01-01

To investigate the effects of different storage periods of alginate impressions on digital model accuracy. A total of 105 impressions were taken from a master model with three different brands of alginates and were poured into stone models in five different storage periods. In all, 21 stone models were poured and immediately were scanned, and 21 digital models were prepared. The remaining 84 impressions were poured after 1, 2, 3, and 4 days, respectively. Five linear measurements were made by three researchers on the master model, the stone models, and the digital models. Time-dependent deformation of alginate impressions at different storage periods and the accuracy of traditional stone models and digital models were evaluated separately. Both the stone models and the digital models were highly correlated with the master model. Significant deformities in the alginate impressions were noted at different storage periods of 1 to 4 days. Alginate impressions of different brands also showed significant differences between each other on the first, third, and fourth days. Digital orthodontic models are as reliable as traditional stone models and probably will become the standard for orthodontic clinical use. Storing alginate impressions in sealed plastic bags for up to 4 days caused statistically significant deformation of alginate impressions, but the magnitude of these deformations did not appear to be clinically relevant and had no adverse effect on digital modeling.

Encapsulation of Lactobacillus kefiri in alginate microbeads using a double novel aerosol technique.

PubMed

Demitri, Christian; Lamanna, Leonardo; De Benedetto, Egidio; Damiano, Fabrizio; Cappello, Maria Stella; Siculella, Luisa; Sannino, Alessandro

2017-08-01

Alginate micro beads containing Lactobacillus kefiri (the principal bacteria present in the kefir probiotic drink) were produced by a novel technique based on dual aerosols spaying of alginate based solution and CaCl 2 as cross linking agent. Carboxymethylcellulose (CMC) has been also added to the alginate in order to change the physic-chemical properties (viscosity and permeability) of the microbeads. Calcium alginate and CMC are biopolymers that can be used for developing oral drug-delivery systems. These biopolymers have been reported to show a pH-dependent swelling behaviour. Calcium alginate and CMC have also been known to possess an excellent mucoadhesive property. The loaded microbeads have been characterized in terms of morphology, chemical composition and stability in different conditions mimicking the gastric environment. In this study, we demonstrate the feasibility of a continuous fabrication of alginate microbeads in a range of 50-70μm size, encapsulating L. kefiri as active ingredient. The technique involves the use of a double aerosols of alginate based solution and CaCl 2 as crosslinking agent. Moreover, the encapsulation process was proved to be effective and not detrimental to bacteria viability. At the same time, it was verified the protective efficacy of the microcapsules against the gastric environment using both SGF pH1.2 (fasted state) and pH2.2 (feed state). Copyright © 2017 Elsevier B.V. All rights reserved.

pH-Sensitive Microparticles with Matrix-Dispersed Active Agent

NASA Technical Reports Server (NTRS)

Calle, Luz M. (Inventor); Jolley, Scott T. (Inventor); Buhrow, Jerry W. (Inventor); Li, Wenyan (Inventor)

2014-01-01

Methods to produce pH-sensitive microparticles that have an active agent dispersed in a polymer matrix have certain advantages over microcapsules with an active agent encapsulated in an interior compartment/core inside of a polymer wall. The current invention relates to pH-sensitive microparticles that have a corrosion-detecting or corrosion-inhibiting active agent or active agents dispersed within a polymer matrix of the microparticles. The pH-sensitive microparticles can be used in various coating compositions on metal objects for corrosion detecting and/or inhibiting.

Alginate Inhibits Iron Absorption from Ferrous Gluconate in a Randomized Controlled Trial and Reduces Iron Uptake into Caco-2 Cells

PubMed Central

Wawer, Anna A.; Harvey, Linda J.; Dainty, Jack R.; Perez-Moral, Natalia; Sharp, Paul; Fairweather-Tait, Susan J.

2014-01-01

Previous in vitro results indicated that alginate beads might be a useful vehicle for food iron fortification. A human study was undertaken to test the hypothesis that alginate enhances iron absorption. A randomised, single blinded, cross-over trial was carried out in which iron absorption was measured from serum iron appearance after a test meal. Overnight-fasted volunteers (n = 15) were given a test meal of 200 g cola-flavoured jelly plus 21 mg iron as ferrous gluconate, either in alginate beads mixed into the jelly or in a capsule. Iron absorption was lower from the alginate beads than from ferrous gluconate (8.5% and 12.6% respectively, p = 0.003). Sub-group B (n = 9) consumed the test meals together with 600 mg calcium to determine whether alginate modified the inhibitory effect of calcium. Calcium reduced iron absorption from ferrous gluconate by 51%, from 11.5% to 5.6% (p = 0.014), and from alginate beads by 37%, from 8.3% to 5.2% (p = 0.009). In vitro studies using Caco-2 cells were designed to explore the reasons for the difference between the previous in vitro findings and the human study; confirmed the inhibitory effect of alginate. Beads similar to those used in the human study were subjected to simulated gastrointestinal digestion, with and without cola jelly, and the digestate applied to Caco-2 cells. Both alginate and cola jelly significantly reduced iron uptake into the cells, by 34% (p = 0.009) and 35% (p = 0.003) respectively. The combination of cola jelly and calcium produced a very low ferritin response, 16.5% (p<0.001) of that observed with ferrous gluconate alone. The results of these studies demonstrate that alginate beads are not a useful delivery system for soluble salts of iron for the purpose of food fortification. Trial Registration ClinicalTrials.gov NCT01528644 PMID:25391138

Ag/alginate nanofiber membrane for flexible electronic skin

NASA Astrophysics Data System (ADS)

Hu, Wei-Peng; Zhang, Bin; Zhang, Jun; Luo, Wei-Ling; Guo, Ya; Chen, Shao-Juan; Yun, Mao-Jin; Ramakrishna, Seeram; Long, Yun-Ze

2017-11-01

Flexible electronic skin has stimulated significant interest due to its widespread applications in the fields of human-machine interactivity, smart robots and health monitoring. As typical elements of electrical skin, the fabrication process of most pressure sensors combined nanomaterials and PDMS films are redundant, expensive and complicated, and their unknown biological toxicity could not be widely used in electronic skin. Hence, we report a novel, cost-effective and antibacterial approach to immobilizing silver nanoparticles into-electrospun Na-alginate nanofibers. Due to the unique role of carboxyl and hydroxyl groups in Na-alginate, the silver nanopaticles with 30 nm size in diameter were uniformly distributed inside and outside the alginate nanofibers, which obtained pressure sensor shows stable response, including an ultralow detection limited (1 pa) and high durability (>1000 cycles). Notably, the pressure sensor fabricated by these Ag/alginate nanofibers could not only follow human respiration but also accurately distinguish words like ‘Nano’ and ‘Perfect’ spoke by a tester. Interestingly, the pixelated sensor arrays based on these Ag/alginate nanofibers could monitor distribution of objects and reflect their weight by measuring the different current values. Moreover, these Ag/alginate nanofibers exhibit great antibacterial activity, implying the great potential application in artificial electronic skin.

Microfluidic Synthesis of Ca-Alginate Microcapsules for Self-Healing of Bituminous Binder.

PubMed

Shu, Benan; Wu, Shaopeng; Dong, Lijie; Wang, Qing; Liu, Quantao

2018-04-19

This work aims to develop an original alginate micro-emulsion combining with droplets microfluidic method to produce multinuclear Ca-alginate microcapsules containing rejuvenator for the self-healing of bituminous binder. The sizes of the Ca-alginate microcapsules could be easily controlled by tuning flow rates of the continuous and dispersed phases. The addition of a surfactant Tween80 not only improved the stability of the emulsion, but it also effectively reduced the size of the microcapsules. Size predictive mathematical model of the microcapsules was proposed through the analysis of fluid force. Optical microscope and remote Fourier infrared test confirmed the multinuclear structure of Ca-alginate microcapsules. Thermogravimetric analysis showed that the microcapsules coated with nearly 40% rejuvenator and they remained intact during the preparation of bitumen specimen at 135 °C. Micro self-healing process of bituminous binder with multinuclear Ca-alginate microcapsules containing rejuvenator was monitored and showed enhanced self-healing performance. Tensile stress-recovery test revealed that the recovery rate increased by 32.08% (in the case of 5% microcapsules), which meant that the Ca-alginate microcapsules containing rejuvenator could effectively enhance the self-healing property of bituminous binder.

Empirical study of alginate impression materials by customized proportioning system

PubMed Central

2016-01-01

PURPOSE Alginate mixers available in the market do not have the automatic proportioning unit. In this study, an automatic proportioning unit for the alginate mixer and controller software were designed and produced for a new automatic proportioning unit. With this device, it was ensured that proportioning operation could arrange weight-based alginate impression materials. MATERIALS AND METHODS The variation of coefficient in the tested groups was compared with the manual proportioning. Compression tension and tear tests were conducted to determine the mechanical properties of alginate impression materials. The experimental data were statistically analyzed using one way ANOVA and Tukey test at the 0.05 level of significance. RESULTS No statistically significant differences in modulus of elastisity (P>0.3), tensional/compresional strength (P>0.3), resilience (P>0.2), strain in failure (P>0.4), and tear energy (P>0.7) of alginate impression materials were seen. However, a decrease in the standard deviation of tested groups was observed when the customized machine was used. To verify the efficiency of the system, powder and powder/water mixing were weighed and significant decrease was observed. CONCLUSION It was possible to obtain more mechanically stable alginate impression materials by using the custom-made proportioning unit. PMID:27826387

Alginate: A Versatile Biomaterial to Encapsulate Isolated Ovarian Follicles.

PubMed

Vanacker, Julie; Amorim, Christiani A

2017-07-01

In vitro culture of ovarian follicles isolated or enclosed in ovarian tissue fragments and grafting of isolated ovarian follicles represent a potential alternative to restore fertility in cancer patients who cannot undergo cryopreservation of embryos or oocytes or transplantation of frozen-thawed ovarian tissue. In this regard, respecting the three-dimensional (3D) architecture of isolated follicles is crucial to maintaining their proper follicular physiology. To this end, alginate hydrogel has been widely investigated using follicles from numerous animal species, yielding promising results. The goal of this review is therefore to provide an overview of alginate applications utilizing the biomaterial as a scaffold for 3D encapsulation of isolated ovarian follicles. Different methods of isolated follicle encapsulation in alginate are discussed in this review, as its use of 3D alginate culture systems as a tool for in vitro follicle analysis. Possible improvements of this matrix, namely modification with arginine-glycine-aspartic acid peptide or combination with fibrin, are also summarized. Encouraging results have been obtained in different animal models, and particularly with isolated follicles encapsulated in alginate matrices and grafted to mice. This summary is designed to guide the reader towards development of next-generation alginate scaffolds, with enhanced properties for follicle encapsulation.

Performance evaluation of bipolar and tripolar excitations during nozzle-jetting-based alginate microsphere fabrication

NASA Astrophysics Data System (ADS)

Herran, C. Leigh; Huang, Yong; Chai, Wenxuan

2012-08-01

Microspheres, small spherical (polymeric) particles with or without second phase materials embedded or encapsulated, are important for many biomedical applications such as drug delivery and organ printing. Scale-up fabrication with the ability to precisely control the microsphere size and morphology has always been of great manufacturing interest. The objective of this work is to experimentally study the performance differences of bipolar and tripolar excitation waveforms in using drop-on-demand (DOD)-based single nozzle jetting for alginate microsphere fabrication. The fabrication performance has been evaluated based on the formability of alginate microspheres as a function of materials properties (sodium alginate and calcium chloride concentrations) and operating conditions. The operating conditions for each excitation include voltage rise/fall times, dwell times and excitation voltage amplitudes. Overall, the bipolar excitation is more robust in making spherical, monodispersed alginate microspheres as good microspheres for its wide working range of material properties and operating conditions, especially during the fabrication of highly viscous materials such as the 2% sodium alginate solution. For both bipolar and tripolar excitations, the sodium alginate concentration and the voltage dwell times should be carefully selected to achieve good microsphere formability.

Transcriptome analysis revealed anti-obesity effects of the Sodium Alginate in high-fat diet -induced obese mice.

PubMed

Wang, Xiong; Liu, Fang; Gao, Yuan; Xue, Chang-Hu; Li, Robert W; Tang, Qing-Juan

2018-04-10

Human obesity and overweight, caused by accumulated of fat, is the most commonly phenomenon from all over the world, especially in Western countries and Chinese mainland during the past three decades. Sodium Alginate, a polysaccharide extracted from brown seaweeds, has been proved its strong ability on body weight loss and anti-inflammatory response. However, no studies have been explored the effects of Sodium Alginate on colonic transcriptome, especially in obese individuals. Therefore, the current study was designed to detect whether Sodium Alginate could remit obesity and ease chronic metabolism disease through strengthening the bio-functionality of the lower intestine, particularly in colon. The data showed after Sodium Alginate gavaged for four weeks, the body weight, fat accumulation, triglyceride and total cholesterol were ameliorated in high fat diet induced obese mice. Sodium Alginate also improved the blood glucose level and lipopolysaccharides in serum. Furthermore, data from RNA sequence indicated that there were significantly changes in several genes, which involved in lipid metabolism and carbohydrate metabolism. In conclusion, these results suggested that Sodium Alginate could effectively suppress obesity and obesity related metabolic syndromes, due to the colonic transcriptome changes. Copyright © 2018. Published by Elsevier B.V.

Light-addressable electrodeposition of cell-encapsulated alginate hydrogels for a cellular microarray using a digital micromirror device

PubMed Central

Huang, Shih-Hao; Hsueh, Hui-Jung; Jiang, Yeu-Long

2011-01-01

This paper describes a light-addressable electrolytic system used to perform an electrodeposition of calcium alginate hydrogels using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-anode to electrolytically produce protons, which can lead to a decreased pH gradient. The low pH generated at the anode can locally release calcium ions from insoluble calcium carbonate (CaCO3) to cause gelation of calcium alginate through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressable electrodeposition of calcium alginate hydrogels with different shapes and sizes, as well as multiplexed micropatterning was performed. The effects of the concentration of the alginate and CaCO3 solutions on the dimensional resolution of alginate hydrogel formation were experimentally examined. A 3 × 3 array of cell-encapsulated alginate hydrogels was also successfully demonstrated through light-addressable electrodeposition. Our proposed method provides a programmable method for the spatiotemporally controllable assembly of cell populations into cellular microarrays and could have a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery. PMID:22685500

Light-addressable electrodeposition of cell-encapsulated alginate hydrogels for a cellular microarray using a digital micromirror device.

PubMed

Huang, Shih-Hao; Hsueh, Hui-Jung; Jiang, Yeu-Long

2011-09-01

This paper describes a light-addressable electrolytic system used to perform an electrodeposition of calcium alginate hydrogels using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-anode to electrolytically produce protons, which can lead to a decreased pH gradient. The low pH generated at the anode can locally release calcium ions from insoluble calcium carbonate (CaCO(3)) to cause gelation of calcium alginate through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressable electrodeposition of calcium alginate hydrogels with different shapes and sizes, as well as multiplexed micropatterning was performed. The effects of the concentration of the alginate and CaCO(3) solutions on the dimensional resolution of alginate hydrogel formation were experimentally examined. A 3 × 3 array of cell-encapsulated alginate hydrogels was also successfully demonstrated through light-addressable electrodeposition. Our proposed method provides a programmable method for the spatiotemporally controllable assembly of cell populations into cellular microarrays and could have a wide range of biological applications in cell-based biosensing, toxicology, and drug discovery.

Development of a cell culture surface conversion technique using alginate thin film for evaluating effect upon cellular differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakashima, Y., E-mail: yuta-n@mech.kumamoto-u.ac.jp; Graduate School of Science and Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube 755-8611; Tsusu, K.

2014-06-15

Here, we sought to develop a cell culture surface conversion technique that would not damage living cells. An alginate thin film, formed on a glass plate by spin coating of sodium alginate solution and dipping into calcium chloride solution, was used to inhibit adhesion of cells. The film could be removed by ethylenediaminetetraacetate (EDTA) at any time during cell culture, permitting observation of cellular responses to conversion of the culture surface in real time. Additionally, we demonstrated the validity of the alginate thin film coating method and the performance of the film. The thickness of the alginate thin film wasmore » controlled by varying the rotation speed during spin coating. Moreover, the alginate thin film completely inhibited the adhesion of cultured cells to the culture surface, irrespective of the thickness of the film. When the alginate thin film was removed from the culture surface by EDTA, the cultured cells adhered to the culture surface, and their morphology changed. Finally, we achieved effective differentiation of C2C12 myoblasts into myotube cells by cell culture on the convertible culture surface, demonstrating the utility of our novel technique.« less

Self-emulsifying excipient platform for improving technological properties of alginate-hydroxypropylcellulose pellets.

PubMed

Mannina, Paolo; Segale, Lorena; Giovannelli, Lorella; Bonda, Andrea Foglio; Pattarino, Franco

2016-02-29

In this work, alginate, alginate-pectin and alginate-hydroxypropylcellulose pellets were produced by ionotropic gelation and characterized. Ibuprofen was selected as model drug; it was suspended in the polymeric solution in crystalline form or dissolved in a self-emulsifying phase and then dispersed into the polymeric solution. The self-emulsifying excipient platform composed of Labrasol (PEG-8 caprylic/capric glycerides) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), able to solubilize the drug was used to improve the technological and biopharmaceutical properties of the alginate pellets. The pellets had diameters between 1317 and 2026 μm and a high drug content (>51%). DSC analysis showed the amorphous state of drug in the pellets containing the self-emulsifying phase. All the systems restricted drug release in conditions simulating the gastric environment and made the drug completely available at a pH value typical for the intestine. Only alginate-HPC systems containing the drug solubilized into the self-emulsifying phase showed the ability to partially control the release of ibuprofen at neutral pH. The self-emulsifying excipient platform is a useful tool to improve technological and biopharmaceutical properties of alginate-HPC pellets. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of comprehensive function of factors on retention behavior of microparticles in gravitational field-flow fractionation.

PubMed

Guo, Shuang; Qiu, Bai-Ling; Zhu, Chen-Qi; Yang, Ya-Ya Gao; Wu, Di; Liang, Qi-Hui; Han, Nan-Yin

2016-09-15

Gravitational field-flow fractionation (GrFFF) is a useful technique for separation and characterization for micrometer-sized particles. Elution behavior of micrometer-sized particles in GrFFF was researched in this study. Particles in GrFFF channel are subject to hydrodynamic lift forces (HLF), fluid inertial forces and gravity, which drive them to different velocities by carrier flow, resulting in a size-based separation. Effects of ionic strength, flow rate and viscosity as well as methanol were investigated using polystyrene latex beads as model particles. This study is devoted to experimental verification of the effect of every factor and their comprehensive function. All experiments were performed to show isolated influence of every variable factor. The orthogonal design test was used to evaluate various factors comprehensively. Results suggested that retention ratio of particles increases with increasing flow rate or the viscosity of carrier liquid by adjusting external forces acting on particles. In addition, retention ratio increases as ionic strength decreases because of decreased electrostatic repulsion between particles and channel accumulation wall. As far as methanol, there is no general trend due to the change of both density and viscosity. On the basis of orthogonal design test it was found that viscosity of carrier liquid plays a significant role in determining resolution of micrometer-sized particles in GrFFF. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material.

PubMed

Priyadarshini, Balasankar M; Selvan, Subramanian T; Narayanan, Karthikeyan; Fawzy, Amr S

2017-06-22

This study explores the delivery of novel calcium hydroxide [Ca(OH)₂] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)₂ [Ca(OH)₂/Blank] and CHX-loaded/Ca(OH)₂ microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)₂ microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)₂/Blank were hexagonal-shaped with highest z -average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface "rounded deposits" and a negative-shift in diameter. CHX:Ca(OH)₂/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)₂ microparticles.

Free microparticles-An inducing mechanism of pre-firing in high pressure gas switches for fast linear transformer drivers.

PubMed

Li, Xiaoang; Pei, Zhehao; Wu, Zhicheng; Zhang, Yuzhao; Liu, Xuandong; Li, Yongdong; Zhang, Qiaogen

2018-03-01

Microparticle initiated pre-firing of high pressure gas switches for fast linear transformer drivers (FLTDs) is experimentally and theoretically verified. First, a dual-electrode gas switch equipped with poly-methyl methacrylate baffles is used to capture and collect the microparticles. By analyzing the electrode surfaces and the collecting baffles by a laser scanning confocal microscope, microparticles ranging in size from tens of micrometers to over 100 μm are observed under the typical working conditions of FLTDs. The charging and movement of free microparticles in switch cavity are studied, and the strong DC electric field drives the microparticles to bounce off the electrode. Three different modes of free microparticle motion appear to be responsible for switch pre-firing. (i) Microparticles adhere to the electrode surface and act as a fixed protrusion which distorts the local electric field and initiates the breakdown in the gap. (ii) One particle escapes toward the opposite electrode and causes a near-electrode microdischarge, inducing the breakdown of the residual gap. (iii) Multiple moving microparticles are occasionally in cascade, leading to pre-firing. Finally, as experimental verification, repetitive discharges at ±90 kV are conducted in a three-electrode field-distortion gas switch, with two 8 mm gaps and pressurized with nitrogen. An ultrasonic probe is employed to monitor the bounce signals. In pre-firing incidents, the bounce is detected shortly before the collapse of the voltage waveform, which demonstrates that free microparticles contribute significantly to the mechanism that induces pre-firing in FLTD gas switches.

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications.

PubMed

Mori, Michela; Almeida, Patrick V; Cola, Michela; Anselmi, Giulia; Mäkilä, Ermei; Correia, Alexandra; Salonen, Jarno; Hirvonen, Jouni; Caramella, Carla; Santos, Hélder A

2014-11-01

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Swellable microparticles as carriers for sustained pulmonary drug delivery.

PubMed

El-Sherbiny, Ibrahim M; McGill, Shayna; Smyth, Hugh D C

2010-05-01

In this investigation, novel biodegradable physically crosslinked hydrogel microparticles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug-loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic(R) F-108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D-XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7-41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung.

Liver Cell-Derived Microparticles Activate Hedgehog Signaling and Alter Gene Expression in Hepatic Endothelial Cells

PubMed Central

Witek, Rafal P.; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S.; Cheong, Yeiwon; Fearing, Caitlin M.; Agboola, Kolade M.; Chen, Wei; Diehl, Anna Mae

2013-01-01

Background & Aims Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). Methods MF-HSCs and cholangiocytes were exposed to platelet-derived growth factor (PDGF) to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy (TEM) and immunoblots, and applied to Hh-reporter containing cells. Microparticles were also obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, a Hh signaling inhibitor. Effects on SEC gene expression were evaluated by QRT-PCR and immunoblotting. Finally, Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Results PDGF-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically active Hh ligands. BDL also increased release of Hh-containing exosome-enriched microparticles into plasma and bile. TEM and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Conclusions Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy. PMID:19013163

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

PubMed

Witek, Rafal P; Yang, Liu; Liu, Renshui; Jung, Youngmi; Omenetti, Alessia; Syn, Wing-Kin; Choi, Steve S; Cheong, Yeiwon; Fearing, Caitlin M; Agboola, Kolade M; Chen, Wei; Diehl, Anna Mae

2009-01-01

Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from ligand-producing cells in microparticles and activate Hh signaling in endothelial cells. We studied whether adult liver cell-derived microparticles contain Hh ligands that alter hepatic sinusoidal endothelial cells (SEC). MF-HSC and cholangiocytes were exposed to platelet-derived growth factor to induce Hh ligands; microparticles were isolated from medium, analyzed by transmission electron microscopy and immunoblots, and applied to Hh-reporter-containing cells. Microparticles were obtained from serum and bile of rats after bile duct ligation (BDL) or sham surgery and applied to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor. Effects on SEC gene expression were evaluated by quantitative reverse-transcription polymerase chain reaction and immunoblotting. Hh target gene expression and SEC activation markers were compared in primary SEC and in liver sections from healthy and BDL rats. Platelet-derived growth factor-treated MF-HSC and cholangiocytes released exosome-enriched microparticles containing biologically-active Hh ligands. BDL increased release of Hh-containing exosome-enriched microparticles into plasma and bile. Transmission electron microscopy and immunoblots revealed similarities among microparticles from all sources; all microparticles induced similar Hh-dependent changes in SEC gene expression. SEC from healthy livers did not express Hh target genes or activation markers, but both were up-regulated in SEC after BDL. Hh-containing exosome-enriched microparticles released from liver cells alter hepatic SEC gene expression, suggesting a novel mechanism for cirrhotic vasculopathy.

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

PubMed Central

Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

2013-01-01

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

Barium titanate microparticles as potential carrier platform for lanthanide radionuclides for their use in the treatment of arthritis.

PubMed

Chakraborty, Sudipta; Vimalnath, K V; Sharma, Jyothi; Shetty, Priyalata; Sarma, H D; Chakravarty, Rubel; Prakash, Deep; Sinha, P K; Dash, Ashutosh

2018-06-15

Since the inception of radiation synovectomy, a host of radioactive colloids and microparticles incorporating suitable therapeutic radionuclides have been proposed for the treatment of arthritis. The present article reports the synthesis and evaluation of barium titanate microparticles as an innovative and effective carrier platform for lanthanide radionuclides in the preparation of therapeutic agents for treatment of arthritis. The material was synthesized by mechanochemical route and characterized by X-ray diffraction, scanning electron microscopy, surface area, and particle size distribution analyses. Loading of lanthanide radionuclides ( 166 Ho, 153 Sm, 177 Lu, and 169 Er) on the microparticles was achieved in high yield (> 95%) resulting in the formulation of loaded particulates with excellent radiochemical purities (> 99%). Radiolanthanide-loaded microparticles exhibited excellent in vitro stability in human serum. In vitro diethylene triamine pentaacetic acid challenge study indicated fairly strong chemical association of lanthanides with barium titanate microparticles. Long-term biodistribution studies carried out after administration of 177 Lu-loaded microparticles into one of the knee joints of normal Wistar rats revealed near-complete retention of the formulation (> 96% of the administered radioactivity) within the joint cavity even 14 days post-administration. The excellent localization of the loaded microparticles was further confirmed by sequential whole-body radio-luminescence imaging studies carried out using 166 Ho-loaded microparticles. Copyright © 2018 John Wiley & Sons, Ltd.

Formulation of olfactory-targeted microparticles with tamarind seed polysaccharide to improve nose-to-brain transport of drugs.

PubMed

Yarragudi, Sasi B; Richter, Robert; Lee, Helen; Walker, Greg F; Clarkson, Andrew N; Kumar, Haribalan; Rizwan, Shakila B

2017-05-01

Targeted delivery and retention of drug formulations in the olfactory mucosa, the target site for nose-to-brain drug absorption is a major challenge due to the geometrical complexity of the nose and nasal clearance. Recent modelling data indicates that 10μm-sized microparticles show maximum deposition in the olfactory mucosa. In the present study we tested the hypothesis that 10μm-sized mucoadhesive microparticles would preferentially deposit on, and increase retention of drug on, the olfactory mucosa in a novel 3D-printed human nasal-replica cast under simulated breathing. The naturally occurring mucoadhesive polymer, tamarind seed polysaccharide (TSP) was used to formulate the microparticles using a spray drying technique. Physicochemical properties of microparticles such as size, morphology and mucoadhesiveness was investigated using a combination of laser diffraction, electron microscopy and texture-analysis. Furthermore, FITC-dextrans (5-40kDa) were incorporated in TSP-microparticles as model drugs. Size-dependent permeability of the FITC-dextrans was observed ex vivo using porcine nasal mucosa. Using the human nasal-replica cast, greater deposition of 10μm TSP-microparticles in the olfactory region was observed compared to TSP-microparticles 2μm in size. Collectively, these findings support our hypothesis that 10μm-sized mucoadhesive microparticles can achieve selective deposition and retention of drug in the olfactory mucosa. Copyright © 2017 Elsevier Ltd. All rights reserved.

Quasi-static motion of microparticles at the depinning contact line of an evaporating droplet on PDMS surface

NASA Astrophysics Data System (ADS)

Yu, Ying-Song; Xia, Xue-Lian; Zheng, Xu; Huang, Xianfu; Zhou, Jin-Zhi

2017-09-01

In this paper, evaporation of sessile water droplets containing fluorescent polystyrene (PS) microparticles on polydimethylsiloxane (PDMS) surfaces with different curing ratios was studied experimentally using laser confocal microscopy. At the beginning, there were some microparticles located at the contact line and some microparticles moved towards the line. Due to contact angle hysteresis, at first both the contact line and the microparticles were pinned. With the depinning contact line, the microparticles moved together spontaneously. Using the software ImageJ, the location of contact lines at different time were acquired and the circle centers and radii of the contact lines were obtained via the least square method. Then the average distance of two neighbor contact lines at a certain time interval was obtained to characterize the motion of the contact line. Fitting the distance-time curve at the depinning contact line stage with polynomials and differentiating the polynomials with time, we obtained the velocity and acceleration of both the contact line and the microparticles located at the line. The velocity and the maximum acceleration were, respectively, of the orders of 1 μm/s and 20-200 nm/s2, indicating that the motion of the microparticles located at the depinning contact line was quasi-static. Finally, we presented a theoretical model to describe the quasi-static process, which may help in understanding both self-pinning and depinning of microparticles.

Antifibrotic effect of dexamethasone/alginate-coated silicone sheet in the abraded middle ear mucosa.

PubMed

Jang, Chul Ho; Ahn, Seung Hyun; Kim, Geun Hyung

2016-12-01

Silicone sheet is a material which is commonly used in middle ear surgery to prevent the formation of adhesions between the tympanic membrane and the medial bony wall of the middle ear cavity. However, silicone sheet can induce a tight and hard fibrous capsule in the region of the stapes, and this is particularly common in cases of eustachian tube dysfunction. As a result of the fibrous encapsulation around the silicone sheet, postoperative aeration of the stapes can be interrupted causing poor hearing gain. In this study, we performed an in vitro and in vivo evaluation of the antifibrotic effects of a dexamethasone and alginate (Dx/alginate) coating on silicone sheet. The Dx/alginate-coated silicone sheets were fabricated using a plasma-treatment and coating method. The Dx/alginate-coated silicone sheets effectively limited in vitro fibroblast attachment and proliferation due to the controlled release of Dx, which can be modified by manipulation of the alginate coating. For the in-vivo evaluation, guinea pigs (albino, male, weighing 250g) were divided into two groups, with the control group (n=5) implanted with silicone sheet and the test group (n=5) receiving Dx/alginate-coated silicone sheet. Animals were sacrificed 3 weeks after implantation, and histological analysis was performed using hematoxylin and eosin (H&E) and immunohistochemical staining techniques. Dx/alginate-coated silicone sheets showed marked inhibition of fibrosis in both the in vitro and in vivo studies. Silicone sheet that incorporates a Dx/alginate coating can release Dx and inhibit fibrosis in the middle ear. This material could be utilized in middle ear surgery as a means of preserving proper aeration and hearing gain following ossiculoplasty. Copyright © 2016 Elsevier B.V. All rights reserved.

A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration.

PubMed

Ferreira, Natália Noronha; Perez, Taciane Alvarenga; Pedreiro, Liliane Neves; Prezotti, Fabíola Garavello; Boni, Fernanda Isadora; Cardoso, Valéria Maria de Oliveira; Venâncio, Tiago; Gremião, Maria Palmira Daflon

2017-10-01

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107 KDa and 1.93 for alginate_S and 32 KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200 μm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer-Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.

Assessment of alginate hydrogel degradation in biological tissue using viscosity-sensitive fluorescent dyes

NASA Astrophysics Data System (ADS)

Shkand, Tatiana V.; Chizh, Mykola O.; Sleta, Iryna V.; Sandomirsky, Borys P.; Tatarets, Anatoliy L.; Patsenker, Leonid D.

2016-12-01

The main goal of this study is to investigate a combination of viscosity-sensitive and viscosity-insensitive fluorescent dyes to distinguish different rheological states of hydrogel based biostructural materials and carriers in biological tissues and to assess their corresponding location areas. The research is done in the example of alginate hydrogel stained with viscosity-sensitive dyes Seta-470 and Seta-560 as well as the viscosity-insensitive dye Seta-650. These dyes absorb/emit at 469/518, 565/591 and 651/670 nm, respectively. The rheological state of the alginate, the area of the fluorescence signal and the mass of the dense alginate versus the calcium gluconate concentration utilized for alginate gelation were studied in vitro. The most pronounced change in the fluorescence signal area was found at the same concentrations of calcium gluconate (below ~1%) as the change in the alginate plaque mass. The stained alginate was also implanted in situ in rat hip and myocardium and monitored using fluorescence imaging. In summary, our data indicate that the viscosity sensitive dye in combination with the viscosity-insensitive dye allow tracking the biodegradation of the alginate hydrogel and determining the rheological state of hydrogel in biological tissue, which both should have relevance for research and clinical applications. Using this method we estimated the half-life of the dense alginate hydrogel in a rat hip to be in the order of 4 d and about 6-8 d in rat myocardium. The half-life of the dense hydrogel in the myocardium was found to be long enough to prevent aneurysm rupture of the left ventricle wall, one of the more severe complications of the early post-infarction period.

New Poly(3-hydroxybutyrate) Microparticles with Paclitaxel Sustained Release for Intraperitoneal Administration.

PubMed

Bonartsev, Anton P; Zernov, Anton L; Yakovlev, Sergey G; Zharkova, Irina I; Myshkina, Vera L; Mahina, Tatiana K; Bonartseva, Garina A; Andronova, Natalia V; Smirnova, Galina B; Borisova, Juliya A; Kalishjan, Mikhail S; Shaitan, Konstantin V; Treshalina, Helena M

2017-01-01

Poly(hydroxyalkanoates) (PHA) have recently attracted increasing attention due to their biodegradability and high biocompatibility, which makes them suitable for the development of new prolong drug formulations. This study was conducted to develop new prolong paclitaxel (PTX) formulation based on poly(3- hydroxybutyrate) (PHB) microparticles. PHB microparticles loaded with antitumor cytostatic drug PTX were obtained by spray-drying method using Nano Spray Dryer B-90. The PTX release kinetics in vitro from PHB microparticles and their cytotoxity on murine hepatoma cell line MH-22a were studied. Microparticles antitumor activity in vivo was studied using intraperitoneally (i.p.) transplanted tumor models: murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. Uniform PTX release from PHB-microparticles during 2 months was observed. PTX-loaded PHB microparticles have demonstrated a significant antitumor activity versus pure drug both in vitro in murine hepatoma cells and in vivo when administered i.p. to mice with murine Lewis lung carcinoma and xenografts of human breast cancer RMG1. The developed technique of PTX sustained delivery from PHB-microparticles has therapeutic potential as prolong anticancer drug formulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

PubMed Central

Choy, Young Bin; Patel, Samirkumar R.; Park, Jung-Hwan; McCarey, Bernard E.; Edelhauser, Henry F.

2011-01-01

Purpose. To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. Methods. Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. Results. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. Conclusions. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye. PMID:21245405

Chitosan microparticles: influence of the gelation process on the release profile and oral bioavailability of albendazole, a class II compound.

PubMed

Piccirilli, Gisela N; García, Agustina; Leonardi, Darío; Mamprin, María E; Bolmaro, Raúl E; Salomón, Claudio J; Lamas, María C

2014-11-01

Encapsulation of albendazole, a class II compound, into polymeric microparticles based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve drug dissolution and oral bioavailability. The microparticles were prepared by spray drying technique and further characterized by means of X-ray powder diffractometry, infrared spectroscopy and scanning electron microscopy. The formation of a novel polymeric structure between chitosan and sodium lauryl sulfate, after the internal or external gelation process, was observed by infrared spectroscopy. The efficiency of encapsulation was found to be between 60 and 85% depending on the internal or external gelation process. Almost spherically spray dried microparticles were observed using scanning electron microscopy. In vitro dissolution results indicated that the microparticles prepared by internal gelation released 8% of the drug within 30 min, while the microparticles prepared by external gelation released 67% within 30 min. It was observed that the AUC and Cmax values of ABZ from microparticles were greatly improved, in comparison with the non-encapsulated drug. In conclusion, the release properties and oral bioavailability of albendazole were greatly improved by using spraydried chitosan-sodium lauryl sulphate microparticles.

Fabrication of micro-alginate gel tubes utilizing micro-gelatin fibers

NASA Astrophysics Data System (ADS)

Sakaguchi, Katsuhisa; Arai, Takafumi; Shimizu, Tatsuya; Umezu, Shinjiro

2017-05-01

Tissues engineered utilizing biofabrication techniques have recently been the focus of much attention, because these bioengineered tissues have great potential to improve the quality of life of patients with various hard-to-treat diseases. Most tissues contain micro-tubular structures including blood vessels, lymphatic vessels, and bile canaliculus. Therefore, we bioengineered a micro diameter tube using alginate gel to coat the core gelatin gel. Micro-gelatin fibers were fabricated by the coacervation method and then coated with a very thin alginate gel layer by dipping. A micro diameter alginate tube was produced by dissolving the core gelatin gel. Consequently, these procedures led to the formation of micro-alginate gel tubes of various shapes and sizes. This biofabrication technique should contribute to tissue engineering research fields.

The release of alginate lyase from growing Pseudomonas syringae pathovar phaseolicola

NASA Technical Reports Server (NTRS)

Ott, C. M.; Day, D. F.; Koenig, D. W.; Pierson, D. L.

2001-01-01

Pseudomonas syringae pathovar phaseolicola, which produces alginate during stationary growth phase, displayed elevated extracellular alginate lyase activity during both mid-exponential and late-stationary growth phases of batch growth. Intracellular activity remained below 22% of the total activity during exponential growth, suggesting that alginate lyase has an extracellular function for this organism. Extracellular enzyme activity in continuous cultures, grown in either nutrient broth or glucose-simple salts medium, peaked at 60% of the washout rate, although nutrient broth-grown cultures displayed more than twice the activity per gram of cell mass. These results imply that growth rate, nutritional composition, or both initiate a release of alginate lyase from viable P. syringae pv. phaseolicola, which could modify its entrapping biofilm.

The Alginate Demonstration: Polymers, Food Science, and Ion Exchange

NASA Astrophysics Data System (ADS)

Waldman, Amy Sue; Schechinger, Linda; Govindarajoo, Geeta; Nowick, James S.; Pignolet, Louis H.

1998-11-01

We have recently devised a polymer demonstration involving the crosslinking and decrosslinking of alginate, a polysaccharide isolated from seaweed. The polymer is composed of D-mannuronic acid and L-guluronic acid subunits and is a component of cell walls. It is commonly used as a thickener in foods such as ice cream and fruit-filled snacks. For the demonstration, a 2% solution of sodium alginate is poured into a 1% solution of calcium chloride. Nontoxic calcium alginate "worms" form due to crosslinking of the polymer. Alternatively, the commercially available antacid Gaviscon can be used as a source of sodium alginate. The crosslinks can then be broken by shaking the worms in brine. The demonstration is a fine addition to any chemical educator's repertoire of polymer experiments.

Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats.

PubMed

Nettey, Henry; Allotey-Babington, Grace Lovia; Somuah, Isaac; Banga, N'guessan Benoit; Afrane, Barima; Amponsah, Seth Kwabena; Annor, Henrietta; Darko, Henry; Hanson, Kwame; Aidoo, Anoa; Broni, Marisa Nyarkoa; Sasu, Clement; Nyarko, Alexander

2017-02-01

The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with C max , AUC 0→48 and t 1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.

Catechin-loaded Eudragit microparticles for the management of diabetes: formulation, characterization and in vivo evaluation of antidiabetic efficacy.

PubMed

Meena, Kedar Prasad; Vijayakumar, Mahalingam Rajamanickam; Dwibedy, Priti S

2017-06-01

Catechin (CT) is natural molecule proved for antidiabetic activity. Clinical application of CT is highly restricted because of its low bioavailability and ineffectiveness in in vivo conditions. Therefore, the main objective of the present investigation was to formulate CT-loaded Eudragit RS 100 microparticles and evaluated for its potential against diabetes. CT microparticles showing highest entrapment efficiency of 92.3 ± 6.5% and higher percentage yield of 63.46 ± 4.3% was selected as optimised formulation. CT microparticles treated rats showed significantly lower blood glucose, cholesterol, LDL, free fatty acid and triglyceride concentrations in comparison to pristine CT-treated rats. The glucose and lipid profiles of microparticle formulation were akin to normal rats. Moreover, CT microparticles did not produce obesity even after 60 days which is a comment side effect of antidiabetic drugs. These results indicate that the CT microparticles can be applied as potential and safe carrier for the treatment of diabetes.

Patterning and manipulating microparticles into a three-dimensional matrix using standing surface acoustic waves

NASA Astrophysics Data System (ADS)

Nguyen, T. D.; Tran, V. T.; Fu, Y. Q.; Du, H.

2018-05-01

A method based on standing surface acoustic waves (SSAWs) is proposed to pattern and manipulate microparticles into a three-dimensional (3D) matrix inside a microchamber. An optical prism is used to observe the 3D alignment and patterning of the microparticles in the vertical and horizontal planes simultaneously. The acoustic radiation force effectively patterns the microparticles into lines of 3D space or crystal-lattice-like matrix patterns. A microparticle can be positioned precisely at a specified vertical location by balancing the forces of acoustic radiation, drag, buoyancy, and gravity acting on the microparticle. Experiments and finite-element numerical simulations both show that the acoustic radiation force increases gradually from the bottom of the chamber to the top, and microparticles can be moved up or down simply by adjusting the applied SSAW power. Our method has great potential for acoustofluidic applications, building the large-scale structures associated with biological objects and artificial neuron networks.

Investigation of Water Absorption and Diffusion in Microparticles Containing Xylitol to Provide a Cooling Effect by Thermal Analysis

NASA Astrophysics Data System (ADS)

Salaün, F.; Bedek, G.; Devaux, E.; Dupont, D.; Deranton, D.

2009-08-01

Polyurethane microparticles containing xylitol as a sweat sensor system were prepared by interfacial polymerization. The structural and thermal properties of the resultant microparticles were studied. The surface morphology and chemical structure of microparticles were investigated using an optical microscope (OM) and a Fourier-transform infrared spectroscope (FTIR), respectively. The thermal properties of samples were investigated by thermogravimetric analysis (TGA) and by differential scanning calorimetry (DSC). Thus, two types of microparticles were synthesized by varying the percentage of monomers introduced. The obtained morphology is directly related to the synthesis conditions. DSC analysis indicated that the mass content of crystalline xylitol was up to 63.8 %, which resulted in a high enthalpy of dilution of 127.7 J · g-1. Furthermore, the water release rate monitored by TGA analysis was found to be faster from the microparticles than from raw xylitol. Thus, the microparticles could be applied for thermal energy storage and moisture sensor enhancement.

Facile Synthesis and Characterization of Ag₃PO₄ Microparticles for Degradation of Organic Dyestuffs under White-Light Light-Emitting-Diode Irradiation.

PubMed

Tseng, Chi-Shun; Wu, Tsunghsueh; Lin, Yang-Wei

2018-04-30

This study demonstrated facile synthesis of silver phosphate (Ag₃PO₄) photocatalysts for the degradation of organic contaminants. Ag₃PO₄ microparticles from different concentrations of precursor, AgNO₃, were produced and characterized by scanning electron microscopy, powder X-ray diffraction, and UV⁻visible diffuse reflectance spectroscopy. Degradation rates of methylene blue (MB) and phenol were measured in the presence of microparticles under low-power white-light light-emitting-diode (LED) irradiation and the reaction rate followed pseudo-first-order kinetics. The prepared Ag₃PO₄ microparticles displayed considerably high photocatalytic activity (>99.8% degradation within 10 min). This can be attributed to the microparticles' large surface area, the low recombination rate of electron⁻hole pairs and the higher charge separation efficiency. The practicality of the Ag₃PO₄ microparticles was validated by the degradation of MB, methyl red, acid blue 1 and rhodamine B under sunlight in environmental water samples, demonstrating the benefit of the high photocatalytic activity from Ag₃PO₄ microparticles.

Preparation of Starch/Gelatin Blend Microparticles by a Water-in-Oil Emulsion Method for Controlled Release Drug Delivery.

PubMed

Phromsopha, Theeraphol; Baimark, Yodthong

2014-01-01

Information on the preparation and properties of starch/gelatin blend microparticles with and without crosslinking for drug delivery is presented. The blend microparticles were prepared by the water-in-oil emulsion solvent diffusion method. Glutaraldehyde and methylene blue were used as the crosslinker and the water-soluble drug model, respectively. The blend microparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy. The functional groups of the starch and gelatin blend matrices were determined from the FTIR spectra. Blend microparticles with a nearly spherical shape and internal porous structure were observed from SEM images. The average particle size of the gelatin microparticles depended on the crosslinker ratio but not on the starch/gelatin blend ratio. The in vitro drug release content significantly decreased as the crosslinker ratio increased and the starch blend ratio decreased. The results demonstrated that the starch/gelatin blend microparticles should be a useful controlled release delivery carrier for water-soluble drugs.

Preparation of Starch/Gelatin Blend Microparticles by a Water-in-Oil Emulsion Method for Controlled Release Drug Delivery

PubMed Central

Phromsopha, Theeraphol; Baimark, Yodthong

2014-01-01

Information on the preparation and properties of starch/gelatin blend microparticles with and without crosslinking for drug delivery is presented. The blend microparticles were prepared by the water-in-oil emulsion solvent diffusion method. Glutaraldehyde and methylene blue were used as the crosslinker and the water-soluble drug model, respectively. The blend microparticles were characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and UV-Vis spectroscopy. The functional groups of the starch and gelatin blend matrices were determined from the FTIR spectra. Blend microparticles with a nearly spherical shape and internal porous structure were observed from SEM images. The average particle size of the gelatin microparticles depended on the crosslinker ratio but not on the starch/gelatin blend ratio. The in vitro drug release content significantly decreased as the crosslinker ratio increased and the starch blend ratio decreased. The results demonstrated that the starch/gelatin blend microparticles should be a useful controlled release delivery carrier for water-soluble drugs. PMID:24868207

In vitro release kinetics of Tolmetin from tabletted Eudragit microparticles.

PubMed

Pignatello, R; Consoli, P; Puglisi, G

2000-01-01

In a previous paper the preparation has been described, by three different techniques, of microparticles made of Eudragit RS 100 and RL 100 containing a NSAI agent, Tolmetin. Freely flowing microparticles failed to affect significantly the in vitro drug release, which displayed a similar dissolution profile after micro-encapsulation to the free drug powder. Microparticles were then converted into tablets and the effect of compression on drug delivery, as well as that of the presence of co-additives, was studied in the present work. Furthermore, microparticles were also prepared by adding MgO to the polymer matrix, to reduce the sensitivity of the drug to pH changes during its dissolution. Similarly, magnesium stearate was also used for microparticle formation as a droplet stabilizer, in order to reduce particle size and hinder rapid drug release. A mathematical evaluation, by using two semi-empirical equations, was applied to evaluate the influence of dissolution and diffusion phenomena upon drug release from microparticle tablets.

Aluminum silicide microparticles transformed from aluminum thin films by hypoeutectic interdiffusion

PubMed Central

2014-01-01

Aluminum silicide microparticles with oxidized rough surfaces were formed on Si substrates through a spontaneous granulation process of Al films. This microparticle formation was caused by interdiffusion of Al and Si atoms at hypoeutectic temperatures of Al-Si systems, which was driven by compressive stress stored in Al films. The size, density, and the composition of the microparticles could be controlled by adjusting the annealing temperature, time, and the film thickness. High-density microparticles of a size around 10 μm and with an atomic ratio of Si/Al of approximately 0.8 were obtained when a 90-nm-thick Al film on Si substrate was annealed for 9 h at 550°C. The microparticle formation resulted in a rapid increase of the sheet resistance, which is a consequence of substantial consumption of Al film. This simple route to size- and composition-controllable microparticle formation may lay a foundation stone for the thermoelectric study on Al-Si alloy-based heterogeneous systems. PMID:24994964

Aluminum silicide microparticles transformed from aluminum thin films by hypoeutectic interdiffusion.

PubMed

Noh, Jin-Seo

2014-01-01

Aluminum silicide microparticles with oxidized rough surfaces were formed on Si substrates through a spontaneous granulation process of Al films. This microparticle formation was caused by interdiffusion of Al and Si atoms at hypoeutectic temperatures of Al-Si systems, which was driven by compressive stress stored in Al films. The size, density, and the composition of the microparticles could be controlled by adjusting the annealing temperature, time, and the film thickness. High-density microparticles of a size around 10 μm and with an atomic ratio of Si/Al of approximately 0.8 were obtained when a 90-nm-thick Al film on Si substrate was annealed for 9 h at 550°C. The microparticle formation resulted in a rapid increase of the sheet resistance, which is a consequence of substantial consumption of Al film. This simple route to size- and composition-controllable microparticle formation may lay a foundation stone for the thermoelectric study on Al-Si alloy-based heterogeneous systems.

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation.

PubMed

Saito, Shunnichi; Nollet, Kenneth E; Ngoma, Alain M; Ono, Takako; Ohto, Hitoshi

2018-02-01

Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis.

Cell-derived microparticles in haemostasis and vascular medicine.

PubMed

Burnier, Laurent; Fontana, Pierre; Kwak, Brenda R; Angelillo-Scherrer, Anne

2009-03-01

Considerable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets - the main source of microparticles - but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

PubMed

Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

2012-01-01

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

Applications of Alginate-Based Bioinks in 3D Bioprinting.

PubMed

Axpe, Eneko; Oyen, Michelle L

2016-11-25

Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine.

Bacterial supersystem for alginate import/metabolism and its environmental and bioenergy applications.

PubMed

Hashimoto, Wataru; Kawai, Shigeyuki; Murata, Kousaku

2010-01-01

Distinct from most alginate-assimilating bacteria that secrete polysaccharide lyases extracellularly, a gram-negative bacterium, Sphingomonas sp. A1 (strain A1), can directly incorporate alginate into its cytoplasm, without degradation, through a "superchannel" consisting of a mouth-like pit on the cell surface, periplasmic binding proteins, and a cytoplasmic membrane-bound ATP-binding cassette transporter. Flagellin homologues function as cell surface alginate receptors essential for expressing the superchannel. Cytoplasmic alginate lyases with different substrate specificities and action modes degrade the polysaccharide to its constituent monosaccharides. The resultant monosaccharides, α-keto acids, are converted to a reduced form by NADPH-dependent reductase, and are finally metabolized in the TCA cycle. Transplantation of the strain A1 superchannel to xenobiotic-degrading sphingomonads enhances bioremediation through the propagation of bacteria with an elevated transport activity. Furthermore, strain A1 cells transformed with Zymomonas mobilis genes for pyruvate decarboxylase and alcohol dehydrogenase II produce considerable amounts of biofuel ethanol from alginate when grown statically. © 2010 Landes Bioscience

Alginate based nanocomposite for microencapsulation of probiotic: Effect of cellulose nanocrystal (CNC) and lecithin.

PubMed

Huq, Tanzina; Fraschini, Carole; Khan, Avik; Riedl, Bernard; Bouchard, Jean; Lacroix, Monique

2017-07-15

Probiotic (Lactobacillus rhamnosus ATCC 9595) was encapsulated in alginate-CNC-lecithin microbeads to produce nutraceutical microcapsules. Addition of CNC and lecithin in alginate microbeads (ACL-1) improved the viability of L. rhamnosus during gastric passage and storage. The compression strength of the freeze-dried ACL-1 microbeads improved 40% compared to alginate microbeads alone. Swelling studies revealed that addition of CNC and lecithin in alginate microbeads decreased (around 47%) the gastric fluid absorption but increased the dissolution time by 20min compared to alginate microbeads (A-0). During transition through the gastric passage, the viability of L. rhamnosus in dried ACL-1 microbeads was increased 37% as compared to A-0 based beads. At 25 and 4°C storage conditions, the viability of L. rhamnosus encapsulated in ACL-1 microbeads decreased by 1.23 and 1.08 log respectively, whereas the encapsulation with A-0 microbeads exhibited a 3.17 and 1.93 log reduction respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sodium alginate as feed additive in cultured sea bream (Sparus aurata): does it modify the quality of the flesh?

PubMed

Peso-Echarri, P; Frontela-Saseta, C; Santaella-Pascual, M; García-Alcázar, A; Abdel, I; Ros-Berruezo, G; Martínez-Graciá, C

2012-11-15

The objective of this study was to evaluate the effect of sodium alginate obtained from brown seaweed as a prebiotic supplement to the feed of reared sea bream (Sparus aurata). Addition of the alginate to a control diet was investigated at both concentrations 2% and 5%. Proximate composition in the flesh were not modified significantly by sodium alginate inclusion in the diet of the sea bream; however the fat and ash content in the specimens supplemented with 5% alginate were found to be significantly higher than those found in individuals who were fed the control diet. No significant differences in mineral content, fatty acid profiles, cholesterol content, texture parameters and sensory acceptability among the three studied groups. Results obtained in this study offer support for the use of alginate as a feed additive in sea bream diets since no significant effects were found in the flesh quality and characteristics of commercial size sea bream. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tough Al-alginate/poly(N-isopropylacrylamide) hydrogel with tunable LCST for soft robotics.

PubMed

Zheng, Wen Jiang; An, Ning; Yang, Jian Hai; Zhou, Jinxiong; Chen, Yong Mei

2015-01-28

Tough Al-alginate/poly(N-isopropylacrylamide) (PNIPAM) hydrogel has been synthesized by introducing an interpenetrating network with hybrid physically cross-linked alginate and chemically cross-linked PNIPAM. Varying the concentration of AlCl3 regulates the mechanical properties of the tough hydrogel and tunes its lower critical solution temperature (LCST) as well. The tough Al-alginate/PNIPAM exhibits 6.3 ± 0.3 MPa of compressive stress and 9.95 of uniaxial stretch. Tunability of LCST is also achieved in a wide range within 22.5-32 °C. A bending beam actuator and a four-arm gripper made of bilayer (Na-alginate/PNIPAM)/(Al-alginate/PNIPAM) hydrogel as prototype of all-hydrogel soft robotics are demonstrated. A finite element (FE) simulation model is developed to simulate the deformation of the soft robotics. The FE simulation not only reproduces the deformation process of performed experiments but also predicts more complicated devices that can be explored in the future. This work broadens the application of temperature-responsive PNIPAM-based hydrogels.

Fabrication of large size alginate beads for three-dimensional cell-cluster culture

NASA Astrophysics Data System (ADS)

Zhang, Zhengtao; Ruan, Meilin; Liu, Hongni; Cao, Yiping; He, Rongxiang

2017-08-01

We fabricated large size alginate beads using a simple microfluidic device under a co-axial injection regime. This device was made by PDMS casting with a mold formed by small diameter metal and polytetrafluorothylene tubes. Droplets of 2% sodium alginate were generated in soybean oil through the device and then cross-linked in a 2% CaCl2 solution, which was mixed tween80 with at a concentration of 0.4 to 40% (w/v). Our results showed that the morphology of the produced alginate beads strongly depends on the tween80 concentration. With the increase of concentration of tween80, the shape of the alginate beads varied from semi-spherical to tailed-spherical, due to the decrease of interface tension between oil and cross-link solution. To access the biocompatibility of the approach, MCF-7 cells were cultured with the alginate beads, showing the formation of cancer cells clusters which might be useful for future studies.

Effect of Oxygen Tension and Medium Components on Monomer Distribution of Alginate.

PubMed

Kıvılcımdan Moral, Çiğdem; Doğan, Özdemir; Sanin, Faika Dilek

2015-06-01

Alginate is a natural biopolymer composed of mannuronic and guluronic acid monomers. It is produced by algae and some species of Azotobacter and Pseudomonas. This study aims to investigate the effect of dissolved oxygen tension (DOT) and growth medium substrate and calcium concentrations on the monomeric composition of alginate produced by Azotobacter vinelandii ATCC® 9046 in a fermenter. Results showed that alginate production increased with increasing DOT from 1 to 5 %. The highest alginate production was obtained as 4.51 g/L under 20 g/L of sucrose and 50 mg/L of calcium at 5 % DOT. At these conditions, alginate was rich in mannuronic acid (up to 61 %) and it was particularly high at low calcium concentration. On the other hand, at extreme conditions such as high DOT level (10 % DOT) and low sucrose concentration (10 g/L), guluronic acid was dominant (ranging between 65 and 100 %).

Applications of Alginate-Based Bioinks in 3D Bioprinting

PubMed Central

Axpe, Eneko; Oyen, Michelle L.

2016-01-01

Three-dimensional (3D) bioprinting is on the cusp of permitting the direct fabrication of artificial living tissue. Multicellular building blocks (bioinks) are dispensed layer by layer and scaled for the target construct. However, only a few materials are able to fulfill the considerable requirements for suitable bioink formulation, a critical component of efficient 3D bioprinting. Alginate, a naturally occurring polysaccharide, is clearly the most commonly employed material in current bioinks. Here, we discuss the benefits and disadvantages of the use of alginate in 3D bioprinting by summarizing the most recent studies that used alginate for printing vascular tissue, bone and cartilage. In addition, other breakthroughs in the use of alginate in bioprinting are discussed, including strategies to improve its structural and degradation characteristics. In this review, we organize the available literature in order to inspire and accelerate novel alginate-based bioink formulations with enhanced properties for future applications in basic research, drug screening and regenerative medicine. PMID:27898010

The biofilm matrix polysaccharides cellulose and alginate both protect Pseudomonas putida mt-2 against reactive oxygen species generated under matric stress and copper exposure.

PubMed

Svenningsen, Nanna B; Martínez-García, Esteban; Nicolaisen, Mette H; de Lorenzo, Victor; Nybroe, Ole

2018-06-01

In natural environments most bacteria live in biofilms embedded in complex matrices of extracellular polymeric substances (EPS). This lifestyle is known to increase protection against environmental stress. Pseudomonas putida mt-2 harbours genes for the production of at least four different EPS polysaccharides, including alginate and cellulose. Little is known about the functional properties of cellulose, while alginate attenuates the accumulation of reactive oxygen species (ROS) caused by matric stress. By using mutants that are deficient in either alginate or cellulose production we show that even cellulose attenuates the accumulation of matric stress-induced ROS for cells in biofilms. Further, both cellulose and alginate attenuate ROS generated through exposure to copper. Interestingly, the two EPS polysaccharides protect cells in both liquid culture and in biofilms against ROS caused by matric stress, indicating that cellulose and alginate do not need to be produced as an integral part of the biofilm lifestyle to provide tolerance towards environmental stressors.

Effect of gamma-irradiation on degradation of alginate.

PubMed

Lee, Dong Wook; Choi, Won Seok; Byun, Myung Woo; Park, Hyun Jin; Yu, Yong-Man; Lee, Chong M

2003-07-30

The aqueous solution of alginate was irradiated by 60Co gamma-rays in the dose range of 10-500 kGy. To assess the effect of irradiation on the degradation of alginate, the irradiation-induced changes in the viscosity, molecular weight, color, monomer composition, and sequence were measured. The molecular weight of raw alginate was reduced from 300000 to 25000 when irradiated at 100 kGy. The degradation rate decreased and the chain breaks per molecule increased with increasing irradiation dose. The viscosity of irradiated alginate solution reached a near minimum as low as at 10 kGy. No appreciable color changes were observed in the samples irradiated at up to 100 kGy, but intense browning occurred beyond 200 kGy. The 13C NMR spectra showed that homopolymeric blocks, MM and GG, increased and the M/G ratio decreased with irradiation. Considering both the level of degradation and the color change of alginate, the optimum irradiation dose was found to be 100 kGy.

Digital microfluidic three-dimensional cell culture and chemical screening platform using alginate hydrogels

PubMed Central

2015-01-01

Electro wetting-on-dielectric (EWOD) digital microfluidics (DMF) can be used to develop improved chemical screening platforms using 3-dimensional (3D) cell culture. Alginate hydrogels are one common method by which a 3D cell culture environment is created. This paper presents a study of alginate gelation on EWOD DMF and investigates designs to obtain uniform alginate hydrogels that can be repeatedly addressed by any desired liquids. A design which allows for gels to be retained in place during liquid delivery and removal without using any physical barriers or hydrophilic patterning of substrates is presented. A proof of concept screening platform is demonstrated by examining the effects of different concentrations of a test chemical on 3D cells in alginate hydrogels. In addition, the temporal effects of the various chemical concentrations on different hydrogel posts are demonstrated, thereby establishing the benefits of an EWOD DMF 3D cell culture and chemical screening platform using alginate hydrogels. PMID:25945142

Mineralized alginate hydrogels using marine carbonates for bone tissue engineering applications.

PubMed

Diaz-Rodriguez, P; Garcia-Triñanes, P; Echezarreta López, M M; Santoveña, A; Landin, M

2018-09-01

The search for an ideal bone tissue replacement has led to the development of new composite materials designed to simulate the complex inorganic/organic structure of bone. The present work is focused on the development of mineralized calcium alginate hydrogels by the addition of marine derived calcium carbonate biomineral particles. Following a novel approach, we were able to obtain calcium carbonate particles of high purity and complex micro and nanostructure dependent on the source material. Three different types of alginates were selected to develop inorganic/organic scaffolds in order to correlate alginate composition with scaffold properties and cell behavior. The incorporation of calcium carbonates into alginate networks was able to promote extracellular matrix mineralization and osteoblastic differentiation of mesenchymal stem cells when added at 7 mg/ml. We demonstrated that the selection of the alginate type and calcium carbonate origin is crucial to obtain adequate systems for bone tissue engineering as they modulate the mechanical properties and cell differentiation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Innovative plasticized alginate obtained by thermo-mechanical mixing: Effect of different biobased polyols systems.

PubMed

Gao, Chengcheng; Pollet, Eric; Avérous, Luc

2017-02-10

Plasticized alginate films with different biobased polyols (glycerol and sorbitol) and their mixtures were successfully prepared by thermo-mechanical mixing instead of the usual casting-evaporation procedure. The microstructure and properties of the different plasticized alginate formulations were investigated by SEM, FTIR, XRD, DMTA and uniaxial tensile tests. SEM and XRD results showed that native alginate particles were largely destructured with the plasticizers (polyols and water), under a thermo-mechanical input. With increasing amount of plasticizers, the samples showed enhanced homogeneity while their thermal and mechanical properties decreased. Compared to sorbitol, glycerol resulted in alginate films with a higher flexibility due to its better plasticization efficiency resulting from its smaller size and higher hydrophilic character. Glycerol and sorbitol mixtures seemed to be an optimum to obtain the best properties. This work showed that thermo-mechanical mixing is a promising method to produce, at large scale, plasticized alginate-based films with improved properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potentiometric titration for determining the composition and stability of metal(II) alginates and pectinates in aqueous solutions

NASA Astrophysics Data System (ADS)

Kaisheva, N. Sh.; Kaishev, A. Sh.

2015-07-01

The compositions and stabilities of Cu2+, Mn2+, Pb2+, Ca2+, Zn2+, Cd2+, Co2+, and Ni2+ alginates and pectinates are determined in aqueous solutions via titrimetry and potentiometry with calculations performed using Bjerrum's method, the curve intersection technique, and the equilibrium shift method. It is found that the interaction between Cu2+ and polyuronides is a stepwise process and, depending on the ligand concentration and the method of determination, Cu2+ alginate can be characterized by its ML, ML2, and ML3 compositions (where M is the metal ion and L is the structural unit of polyuronide) and stability constants logβ = 2.65, 5.00-5.70, and 7.18-7.80, respectively. The compositions of Cu2+ pectinates are ML and ML2 with logβ = 3.00 and 7.64-7.94, respectively. It is concluded that Pb2+, Ca2+, Mn2+, Zn2+, Cd2+, Co2+, and Ni2+ ions form only alginates and pectinates of ML2 composition with logβ values of 3.45 (Pb2+ alginate), 2.20 (Ca2+ alginate), 1.06 (Mn2+ alginate), 3.51 (Pb2+ pectinate), 2.35 (Ca2+ pectinate), and 1.24 (Mn2+ pectinate). The pectinates are shown to be more stable than the alginates, the most stable compounds being those formed by polyuronides and Cu2+. The least stable are those with Mn2+.

Link between alginate reaction front propagation and general reaction diffusion theory.

PubMed

Braschler, Thomas; Valero, Ana; Colella, Ludovica; Pataky, Kristopher; Brugger, Jürgen; Renaud, Philippe

2011-03-15

We provide a common theoretical framework reuniting specific models for the Ca(2+)-alginate system and general reaction diffusion theory along with experimental validation on a microfluidic chip. As a starting point, we use a set of nonlinear, partial differential equations that are traditionally solved numerically: the Mikkelsen-Elgsaeter model. Applying the traveling-wave hypothesis as a major simplification, we obtain an analytical solution. The solution indicates that the fundamental properties of the alginate reaction front are governed by a single dimensionless parameter λ. For small λ values, a large depletion zone accompanies the reaction front. For large λ values, the alginate reacts before having the time to diffuse significantly. We show that the λ parameter is of general importance beyond the alginate model system, as it can be used to classify known solutions for second-order reaction diffusion schemes, along with the novel solution presented here. For experimental validation, we develop a microchip model system, in which the alginate gel formation can be carried out in a highly controlled, essentially 1D environment. The use of a filter barrier enables us to rapidly renew the CaCl(2) solution, while maintaining flow speeds lower than 1 μm/s for the alginate compartment. This allows one to impose an exactly known bulk CaCl(2) concentration and diffusion resistance. This experimental model system, taken together with the theoretical development, enables the determination of the entire set of physicochemical parameters governing the alginate reaction front in a single experiment.

Hybrid 3D printing and electrodeposition approach for controllable 3D alginate hydrogel formation.

PubMed

Shang, Wanfeng; Liu, Yanting; Wan, Wenfeng; Hu, Chengzhi; Liu, Zeyang; Wong, Chin To; Fukuda, Toshio; Shen, Yajing

2017-06-07

Calcium alginate hydrogels are widely used as biocompatible materials in a substantial number of biomedical applications. This paper reports on a hybrid 3D printing and electrodeposition approach for forming 3D calcium alginate hydrogels in a controllable manner. Firstly, a specific 3D hydrogel printing system is developed by integrating a customized ejection syringe with a conventional 3D printer. Then, a mixed solution of sodium alginate and CaCO 3 nanoparticles is filled into the syringe and can be continuously ejected out of the syringe nozzle onto a conductive substrate. When applying a DC voltage (∼5 V) between the substrate (anode) and the nozzle (cathode), the Ca 2+ released from the CaCO 3 particles can crosslink the alginate to form calcium alginate hydrogel on the substrate. To elucidate the gel formation mechanism and better control the gel growth, we can further establish and verify a gel growth model by considering several key parameters, i.e., applied voltage and deposition time. The experimental results indicate that the alginate hydrogel of various 3D structures can be formed by controlling the movement of the 3D printer. A cell viability test is conducted and shows that the encapsulated cells in the gel can maintain a high survival rate (∼99% right after gel formation). This research establishes a reliable method for the controllable formation of 3D calcium alginate hydrogel, exhibiting great potential for use in basic biology and applied biomedical engineering.

Production of tannase by the immobilized cells of Bacillus licheniformis KBR6 in Ca-alginate beads.

PubMed

Mohapatra, P K D; Mondal, K C; Pati, B R

2007-06-01

The present study was aimed at finding the optimal conditions for immobilization of Bacillus licheniformis KBR6 cells in calcium-alginate (Ca-alginate) beads and determining the operational stability during the production of tannin-acyl-hydrolase (tannase) under semicontinous cultivation. The active cells of B. licheniformis KBR6 were immobilized in Ca-alginate and used for the production of tannase. The influence of alginate concentration (5, 10, 20 and 30 g l(-1)) and initial cell loading on enzyme production were studied. The production of tannase increased significantly with increasing alginate concentration and reached a maximum enzyme yield of 0.56 +/- 0.03 U ml(-1) at 20 g l(-1). This was about 1.70-fold higher than that obtained by free cells. The immobilized cells produced tannase consistently over 13 repeated cycles and reached a maximum level at the third cycle. Scanning electron microscope study indicated that the cells in Ca-alginate beads remain in normal shape. The Ca-alginate entrapment is a promising immobilization method of B. licheniformis KBR6 for repeated tannase production. Tannase production by immobilized cells is superior to that of free cells because it leads to higher volumetric activities within the same period of fermentation. This is the first report of tannase production from immobilized bacterial cells. The bacterium under study can produce higher amounts of tannase with respect to other fungal strains within a short cultivation period.

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan.

PubMed

El Maghraby, Gamal M; Elzayat, Ehab M; Alanazi, Fars K

2012-08-01

Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping. Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine. Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release. Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product. Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.

Effect of storage time of extended-pour and conventional alginate impressions on dimensional accuracy of casts.

PubMed

Rohanian, Ahmad; Ommati Shabestari, Ghasem; Zeighami, Somayeh; Samadi, Mohammad Javad; Shamshiri, Ahmad Reza

2014-11-01

Some manufacturers claim to have produced new irreversible hydro-colloids that are able to maintain their dimensional stability during storage. The present study evaluated the effect of storage time on dimensional stability of three alginates: Hydrogum 5, Tropicalgin and Alginoplast. In this experimental in-vitro trial, a total of 90 alginate impressions were made from a Dentoform model using Hydrogum 5, Tropicalgin and Alginoplast alginates. The impressions were stored in a sealed plastic bag without a damp paper towel for 0, 24, 48, 72 and 120 hours and then poured with type III dental stone. Cross-arch (facial of 6 to facial of 6 on the opposite side) and antero-posterior (distal of right first molar to the ipsilateral central incisor) measurements were made with a digital caliper on the casts. Data were analyzed by two-way and one-way ANOVA and Tukey's post-hoc test (P<0.05). Alginate type and the pouring time significantly affected the dimensional stability of alginate impressions (both Ps<0.001). Pouring of Hydrogum 5 impressions can be delayed for up to 120 hours without significant dimensional changes. Alginoplast impressions may be poured after 72 hours, but Tropicalgin should be poured immediately and the storage time should not be more than 24 hours. Immediate pouring of alginate impressions provides the highest accuracy in reproducing the teeth and adjacent tissues; however, this study demonstrated that pouring may be delayed for up to five days using extended-pour (Hydrogum 5) alginates.

A comparative study on the raft chemical properties of various alginate antacid raft-forming products.

PubMed

Dettmar, Peter W; Gil-Gonzalez, Diana; Fisher, Jeanine; Flint, Lucy; Rainforth, Daniel; Moreno-Herrera, Antonio; Potts, Mark

2018-01-01

Research to measure the chemical characterization of alginate rafts for good raft performance and ascertain how formulation can affect chemical parameters. A selection of alginate formulations was investigated all claiming to be proficient raft formers with significance between products established and ranked. Procedures were selected which demonstrated the chemical characterization allowing rafts to effectively impede the reflux into the esophagus or in severe cases to be refluxed preferentially into the esophagus and exert a demulcent effect, with focus of current research on methods which complement previous studies centered on physical properties. The alginate content was analyzed by a newly developed HPLC method. Methods were used to determine the neutralization profile and the acid neutralization within the raft determined along with how raft structure affects neutralization. Alginate content of Gaviscon Double Action (GDA) within the raft was significantly superior (p < .0001) to all competitor products. The two products with the highest raft acid neutralization capacity were GDA and Rennie Duo, the latter product not being a raft former. Raft structure was key and GDA had the right level of porosity to allow for longer duration of neutralization. Alginate formulations require three chemical reactions to take place simultaneously: transformation to alginic acid, sodium carbonate reacting to form carbon dioxide, calcium releasing free calcium ions to bind with alginic acid providing strength to raft formation. GDA was significantly superior (p <.0001) to all other comparators.

Paclitaxel-loaded polymeric microparticles: Quantitative relationships between in vitro drug release rate and in vivo pharmacodynamics

PubMed Central

Tsai, Max; Lu, Ze; Wientjes, M. Guillaume; Au, Jessie L.-S.

2013-01-01

Intraperitoneal therapy (IP) has demonstrated survival advantages in patients with peritoneal cancers, but has not become a widely practiced standard-of-care in part due to local toxicity and sub-optimal drug delivery. Paclitaxel-loaded, polymeric microparticles were developed to overcome these limitations. The present study evaluated the effects of microparticle properties on paclitaxel release (extent and rate) and in vivo pharmacodynamics. In vitro paclitaxel release from microparticles with varying physical characteristics (i.e., particle size, copolymer viscosity and composition) was evaluated. A method was developed to simulate the dosing rate and cumulative dose released in the peritoneal cavity based on the in vitro release data. The relationship between the simulated drug delivery and treatment outcomes of seven microparticle compositions was studied in mice bearing IP human pancreatic tumors, and compared to that of the intravenous Cremophor micellar paclitaxel solution used off-label in previous IP studies. Paclitaxel release from polymeric microparticles in vitro was multi-phasic; release was greater and more rapid from microparticles with lower polymer viscosities and smaller diameters (e.g., viscosity of 0.17 vs. 0.67 dl/g and diameter of 5–6 vs. 50–60 μm). The simulated drug release in the peritoneal cavity linearly correlated with treatment efficacy in mice (r2>0.8, p<0.001). The smaller microparticles, which distribute more evenly in the peritoneal cavity compared to the large microparticles, showed greater dose efficiency. For single treatment, the microparticles demonstrated up to 2-times longer survival extension and 4-times higher dose efficiency, relative to the paclitaxel/Cremophor micellar solution. Upon repeated dosing, the paclitaxel/Cremophor micellar solution showed cumulative toxicity whereas the microparticle that yielded 2-times longer survival did not display cumulative toxicity. The efficacy of IP therapy depended on both temporal and spatial factors that were determined by the characteristics of the drug delivery system. A combination of fast- and slow-releasing microparticles with 5–6 μm diameter provided favorable spatial distribution and optimal drug release for IP therapy. PMID:24056144

Microfluidic production of polymeric functional microparticles

NASA Astrophysics Data System (ADS)

Jiang, Kunqiang

This dissertation focuses on applying droplet-based microfluidics to fabricate new classes of polymeric microparticles with customized properties for various applications. The integration of microfluidic techniques with microparticle engineering allows for unprecedented control over particle size, shape, and functional properties. Specifically, three types of microparticles are discussed here: (1) Magnetic and fluorescent chitosan hydrogel microparticles and their in-situ assembly into higher-order microstructures; (2) Polydimethylsiloxane (PDMS) microbeads with phosphorescent properties for oxygen sensing; (3) Macroporous microparticles as biological immunosensors. First, we describe a microfluidic approach to generate monodisperse chitosan hydrogel microparticles that can be further connected in-situ into higher-order microstructures. Microparticles of the biopolymer chitosan are created continuously by contacting an aqueous solution of chitosan at a microfluidic T-junction with a stream of hexadecane containing a nonionic detergent, followed by downstream crosslinking of the generated droplets by a ternary flow of glutaraldehyde. Functional properties of the microparticles can be easily varied by introducing payloads such as magnetic nanoparticles and/or fluorescent dyes into the chitosan solution. We then use these prepared microparticles as "building blocks" and assemble them into high ordered microstructures, i.e. microchains with controlled geometry and flexibility. Next, we describe a new approach to produce monodisperse microbeads of PDMS using microfluidics. Using a flow-focusing configuration, a PDMS precursor solution is dispersed into microdroplets within an aqueous continuous phase. These droplets are collected and thermally cured off-chip into soft, solid microbeads. In addition, our technique allows for direct integration of payloads, such as an oxygen-sensitive porphyrin dye, into the PDMS microbeads. We then show that the resulting dye-bearing beads can function as non-invasive and real-time oxygen micro-sensors. Finally, we report a co-flow microfluidic method to prepare uniform polymer microparticles with macroporous texture, and investigate their application as discrete immunological biosensors for the detection of biological species. The matrix of such microparticles is based on macroporous polymethacrylate polymers configured with tailored pores ranging from hundreds of nanometers to a few microns. Subsequently, we immobilize bioactive antibodies on the particle surface, and demonstrate the immunological performance of these functionalized porous microbeads over a range of antigen concentrations.

microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers.

PubMed

de Gonzalo-Calvo, David; Cenarro, Ana; Civeira, Fernando; Llorente-Cortes, Vicenta

2016-01-01

microRNA (miRNA) expression profile of extracellular vesicles is a potential tool for clinical practice. Despite the key role of vascular smooth muscle cells (VSMC) in cardiovascular pathology, there is limited information about the presence of miRNAs in microparticles secreted by this cell type, including human coronary artery smooth muscle cells (HCASMC). Here, we tested whether HCASMC-derived microparticles contain miRNAs and the value of these miRNAs as biomarkers. HCASMC and explants from atherosclerotic or non-atherosclerotic areas were obtained from coronary arteries of patients undergoing heart transplant. Plasma samples were collected from: normocholesterolemic controls (N=12) and familial hypercholesterolemia (FH) patients (N=12). Both groups were strictly matched for age, sex and cardiovascular risk factors. Microparticle (0.1-1μm) isolation and characterization was performed using standard techniques. VSMC-enriched miRNAs expression (miR-21-5p, -143-3p, -145-5p, -221-3p and -222-3p) was analyzed using RT-qPCR. Total RNA isolated from HCASMC-derived microparticles contained small RNAs, including VSMC-enriched miRNAs. Exposition of HCASMC to pathophysiological conditions, such as hypercholesterolemia, induced a decrease in the expression level of miR-143-3p and miR-222-3p in microparticles, not in cells. Expression levels of miR-222-3p were lower in circulating microparticles from FH patients compared to normocholesterolemic controls. Microparticles derived from atherosclerotic plaque areas showed a decreased level of miR-143-3p and miR-222-3p compared to non-atherosclerotic areas. We demonstrated for the first time that microparticles secreted by HCASMC contain microRNAs. Hypercholesterolemia alters the microRNA profile of HCASMC-derived microparticles. The miRNA signature of HCASMC-derived microparticles is a source of cardiovascular biomarkers. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material

PubMed Central

Priyadarshini, Balasankar M.; Selvan, Subramanian T.; Narayanan, Karthikeyan; Fawzy, Amr S.

2017-01-01

This study explores the delivery of novel calcium hydroxide [Ca(OH)2] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)2 [Ca(OH)2/Blank] and CHX-loaded/Ca(OH)2 microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)2 microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)2/Blank were hexagonal-shaped with highest z-average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface “rounded deposits” and a negative-shift in diameter. CHX:Ca(OH)2/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)2 microparticles. PMID:28952538

The Young's Modulus, Fracture Stress, and Fracture Strain of Gellan Hydrogels Filled with Whey Protein Microparticles.

PubMed

Lam, Cherry Wing Yu; Ikeda, Shinya

2017-05-01

Texture modifying abilities of whey protein microparticles are expected to be dependent on pH during heat-induced aggregation of whey protein in the microparticulation process. Therefore, whey protein microparticles were prepared at either pH 5.5 or 6.8 and their effects on small and large deformation properties of gellan gels containing whey protein microparticles as fillers were investigated. The majority of whey protein microparticles had diameters around 2 μm. Atomic force microscopy images showed that whey protein microparticles prepared at pH 6.8 partially collapsed and flatted by air-drying, while those prepared at pH 5.5 did not. The Young's modulus of filled gels adjusted to pH 5.5 decreased by the addition of whey protein microparticles, while those of filled gels adjusted to pH 6.8 increased with increasing volume fraction of filler particles. These results suggest that filler particles were weakly bonded to gel matrices at pH 5.5 but strongly at pH 6.8. Whey protein microparticles prepared at pH 5.5 showed more enhanced increases in the Young's modulus than those prepared at pH 6.8 at volume fractions between 0.2 and 0.4, indicating that microparticles prepared at pH 5.5 were mechanically stronger. The fracture stress of filled gels showed trends somewhat similar to those of the Young's modulus, while their fracture strains decreased by the addition of whey protein microparticles in all examined conditions, indicating that the primary effect of these filler particles was to enhance the brittleness of filled gels. © 2017 Institute of Food Technologists®.

Increased levels of circulating platelet derived microparticles in Crohn's disease patients.

PubMed

Tziatzios, Georgios; Polymeros, Dimitrios; Spathis, Aris; Triantafyllou, Maria; Gkolfakis, Paraskevas; Karakitsos, Petros; Dimitriadis, George; Triantafyllou, Konstantinos

2016-10-01

Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. Crohn's disease patients have greater PDMPs (0.31% ± 0.07% versus 0.14% ± 0.04%, p = 0.02) and PDMPs expressing Annexin V (27% ± 2.6% versus 14.6% ± 2.7%, p = 0.002) levels in comparison with healthy controls; however, both microparticles levels are not related with disease activity. Crohn's disease patients on 5-ASA therapy show lower levels of PDMPs in comparison with those on no 5-ASA (0.30% ± 0.07% versus 0.32% ± 0.09%, p = 0.048). Ulcerative colitis patients have similar PDMPs and PDMPs expressing Annexin V levels, compared to healthy controls (p = 0.06 and p = 0.2, respectively) and there is no correlation of both microparticles expression with disease activity. 5-ASA has no effect on both microparticles levels in ulcerative colitis patients. Anti-TNF-α treatment has no effect on study's microparticles expression in Crohn's and ulcerative colitis patients. Circulating levels of platelet derived microparticles are increased only in Crohn's patients, but they do not correlate with disease activity. 5-ASA treatment is associated with lower levels of PDMPs only in Crohn's, while anti-TNF-α treatment does not influence expression of microparticles in inflammatory bowel disease patients.

Association between cell-derived microparticles and adverse events in patients with nonpulsatile left ventricular assist devices

PubMed Central

Nascimbene, Angelo; Hernandez, Ruben; George, Joggy K.; Parker, Anita; Bergeron, Angela L.; Pradhan, Subhashree; Vijayan, K. Vinod; Civitello, Andrew; Simpson, Leo; Nawrot, Maria; Lee, Vei-Vei; Mallidi, Hari R.; Delgado, Reynolds M.; Dong, Jing Fei; Frazier, O.H.

2014-01-01

BACKGROUND Continuous-flow left ventricular assist devices (LVADs) expose blood cells to high shear stress, potentially resulting in the production of microparticles that express phosphatidylserine (PS+) and promote coagulation and inflammation. In this prospective study, we attempted to determine whether PS+ microparticle levels correlate with clinical outcomes in LVAD-supported patients. METHODS We enrolled 20 patients undergoing implantation of the HeartMate II LVAD and 10 healthy controls who provided reference values for the microparticle assays. Plasma was collected before LVAD implantation, at discharge, at 3-month follow-up, and when an adverse clinical event occurred. We quantified PS+ microparticles in the plasma using flow cytometry. RESULTS During the study period, 8 patients developed adverse clinical events: ventricular tachycardia storm (n=1), non–ST-elevation myocardial infarction (n=2), arterial thrombosis (n=2), gastrointestinal bleeding (n=2), and stroke (n=3). Levels of PS+ microparticles were higher in patients at baseline than in healthy controls (2.11%±1.26 vs 0.69±0.46, P=0.007). After LVAD implantation, patient PS+ microparticle levels increased to 2.39%±1.22 at discharge and then leveled to 1.97%±1.25 at 3-month follow-up. Importantly, patients who developed an adverse event had significantly higher levels of PS+ microparticles than did patients with no events (3.82%±1.17 vs 1.57%±0.59, P<0.001), even though the 2 patient groups did not markedly differ in other clinical and hematologic parameters. CONCLUSIONS Our results suggest that an elevation of PS+ microparticle levels may be associated with adverse clinical events. Thus, measuring PS+ microparticle levels in LVAD-supported patients may help identify patients at increased risk for adverse events. PMID:24656391

21 CFR 172.858 - Propylene glycol alginate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Propylene glycol alginate. 172.858 Section 172.858... CONSUMPTION Multipurpose Additives § 172.858 Propylene glycol alginate. The food additive propylene glycol... information required by the act: (1) The name of the additive, “propylene glycol alginate” or “propylene...

21 CFR 172.858 - Propylene glycol alginate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Propylene glycol alginate. 172.858 Section 172.858... CONSUMPTION Multipurpose Additives § 172.858 Propylene glycol alginate. The food additive propylene glycol... information required by the act: (1) The name of the additive, “propylene glycol alginate” or “propylene...

Neurokinin 1 Receptor Mediates Membrane Blebbing and Sheer Stress-Induced Microparticle Formation in HEK293 Cells

PubMed Central

Chen, Panpan; Douglas, Steven D.; Meshki, John; Tuluc, Florin

2012-01-01

Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R) is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP). We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2–10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing. PMID:23024816

Influence of polymeric carrier on the disposition and retention of 20(R)-ginsenoside-rg3-loaded swellable microparticles in the lung.

PubMed

Wang, Xiuhua; Zhang, Xiao; Fan, Linlin; He, Huan; Zhang, Xiaofei; Zhang, Yuyang; Mao, Shirui

2018-02-01

The objective of this study was to investigate the influence of differently charged biocompatible polymers, including chitosan (CS), hyaluronic acid (HA), and hydroxypropyl cellulose (HPC), on the disposition and retention of 20(R)-ginsenoside-rg3 (Rg3)-loaded swellable microparticles in the lung. A high-pressure homogenization method combined with spray drying was used to prepare Rg3-loaded microparticles. In vitro aerodynamic performance of different microparticles was characterized by the Next Generation Impactor (NGI). Retention of the swellable microparticles in the rat lung was investigated using bronchoalveolar lavage fluid method. Influence of drug loading, polymer molecular weight, and polymer charge on the properties of the swellable microparticles was investigated. It was found that drug loading had no significant influence on experimental mass median aerodynamic diameter (MMAD e ) and fine particle fraction (FPF). Increasing polymer molecular weight caused no remarkable change in MMAD e value, but the FPF value decreased with the increase of polymer molecular weight. At the same molecular weight level, polymer structure and charge had no statistical influence on the in vitro aerodynamic properties of the microparticles and lung disposition, but it influenced the swelling and bioadhesion behavior and therefore lung retention profile. Desirable phagocytosis escapement and inhibition of A549 cell proliferation were achieved for the developed swellable microparticles. In conclusion, the lung retention of swellable microparticles can be adjusted by selecting polymeric carriers with different structure and charge.

Properties of iopamidol-incorporated poly(vinyl alcohol) microparticle as an X-ray imaging flow tracer.

PubMed

Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

2011-02-10

We have recently reported on poly(vinyl alcohol) microparticles containing X-ray contrast agent, iopamidol, designed as a flow tracer working in synchrotron X-ray imaging ( Biosens. Bioelectron. 2010 , 25 , 1571 ). Although iopamidol is physically encapsulated in the microparticles, it displays a great contrast enhancement and stable feasibility in in vitro human blood pool. Nonetheless, a direct relation between the absolute amount of incorporated iopamidol and the enhancement in imaging efficiency was not observed. In this study, physical properties of the designed microparticle are systematically investigated experimentally with theoretical interpretation to correlate an enhancement in X-ray imaging efficiency. The compositional ratio of X-ray contrast agent in polymeric microparticle is controlled as 1/1 and 10/1 [contrast agent/polymer microparticle (w/w)] with changed degree of cross-linkings. Flory-Huggins interaction parameter (χ), retractive force (τ) and degree of swelling of the designed polymeric microparticles are investigated. In addition, the hydrodynamic size (D(H)) and ζ-potential are evaluated in terms of environment responsiveness. The physical properties of the designed flow tracer microparticles under a given condition are observed to be strongly related with the X-ray absorption efficiency, which are also supported by the Beer-Lambert-Bouguer law. The designed microparticles are almost nontoxic with a reasonable concentration and time period, enough to be utilized as a flow tracer in various biomedical applications. This study would contribute to the basic understanding on the physical property connected with the imaging efficiency of contrast agents.

Neurokinin 1 receptor mediates membrane blebbing and sheer stress-induced microparticle formation in HEK293 cells.

PubMed

Chen, Panpan; Douglas, Steven D; Meshki, John; Tuluc, Florin

2012-01-01

Cell-derived microparticles participate in intercellular communication similar to the classical messenger systems of small and macro-molecules that bind to specialized membrane receptors. Microparticles have been implicated in the regulation of a variety of complex physiopathologic processes, such as thrombosis, the control of innate and adaptive immunity, and cancer. The neurokinin 1 receptor (NK1R) is a Gq-coupled receptor present on the membrane of a variety of tissues, including neurons in the central and peripheral nervous system, immune cells, endocrine and exocrine glands, and smooth muscle. The endogenous agonist of NK1R is the undecapeptide substance P (SP). We have previously described intracellular signaling mechanisms that regulate NK1R-mediated rapid cell shape changes in HEK293 cells and U373MG cells. In the present study, we show that the activation of NK1R in HEK293 cells, but not in U373MG cells, leads to formation of sheer-stress induced microparticles that stain positive with the membrane-selective fluorescent dye FM 2-10. SP-induced microparticle formation is independent of elevated intracellular calcium concentrations and activation of NK1R present on HEK293-derived microparticles triggers detectable calcium increase in SP-induced microparticles. The ROCK inhibitor Y27632 and the dynamin inhibitor dynasore inhibited membrane blebbing and microparticle formation in HEK293 cells, strongly suggesting that microparticle formation in this cell type is dependent on membrane blebbing.

Alginate: properties and biomedical applications

PubMed Central

Lee, Kuen Yong; Mooney, David J.

2011-01-01

Alginate is a biomaterial that has found numerous applications in biomedical science and engineering due to its favorable properties, including biocompatibility and ease of gelation. Alginate hydrogels have been particularly attractive in wound healing, drug delivery, and tissue engineering applications to date, as these gels retain structural similarity to the extracellular matrices in tissues and can be manipulated to play several critical roles. This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers. PMID:22125349

Mesenchymal stem cells and alginate microcarriers for craniofacial bone tissue engineering: A review.

PubMed

Saltz, Adam; Kandalam, Umadevi

2016-05-01

Craniofacial bone is a complex structure with an intricate anatomical and physiological architecture. The defects that exist in this region therefore require a precise control of osteogenesis in their reconstruction. Unlike traditional surgical intervention, tissue engineering techniques mediate bone development with limited postoperative risk and cost. Alginate stands as the premier polymer in bone repair because of its mild ionotropic gelation and excellent biocompatibility, biodegradability, and injectability. Alginate microcarriers are candidates of choice to mediate cells and accommodate into 3-D environment. Several studies reported the use of alginate microcarriers for delivering cells, drugs, and growth factors. This review will explore the potential use of alginate microcarrier for stem cell systems and its application in craniofacial bone tissue engineering. © 2016 Wiley Periodicals, Inc.

Design and performance of a sericin-alginate interpenetrating network hydrogel for cell and drug delivery.

PubMed

Zhang, Yeshun; Liu, Jia; Huang, Lei; Wang, Zheng; Wang, Lin

2015-07-24

Although alginate hydrogels have been extensively studied for tissue engineering applications, their utilization is limited by poor mechanical strength, rapid drug release, and a lack of cell adhesive ability. Aiming to improve these properties, we employ the interpenetrating hydrogel design rationale. Using alginate and sericin (a natural protein with many unique properties and a major component of silkworm silk), we develop an interpenetrating polymer network (IPN) hydrogel comprising interwoven sericin and alginate double networks. By adjusting the sericin-to-alginate ratios, IPNs' mechanical strength can be adjusted to meet stiffness requirements for various tissue repairs. The IPNs with high sericin content show increased stability during degradation, avoiding pure alginate's early collapse. These IPNs have high swelling ratios, benefiting various applications such as drug delivery. The IPNs sustain controlled drug release with the adjustable rates. Furthermore, these IPNs are adhesive to cells, supporting cell proliferation, long-term survival and migration. Notably, the IPNs inherit sericin's photoluminescent property, enabling bioimaging in vivo. Together, our study indicates that the sericin-alginate IPN hydrogels may serve as a versatile platform for delivering cells and drugs, and suggests that sericin may be a building block broadly applicable for generating IPN networks with other biomaterials for diverse tissue engineering applications.

Stemness of spermatogonial stem cells encapsulated in alginate hydrogel during cryopreservation.

PubMed

Pirnia, A; Parivar, K; Hemadi, M; Yaghmaei, P; Gholami, M

2017-06-01

This study investigated the effect of spermatogonial stem cell encapsulated in alginate hydrogel during cryopreservation, as cells were protected against damage during cryopreservation within the hydrogel. Spermatogonial stem cells were isolated from the testes of Balb/c mice pups (6 days old), purified in laminin-coated dishes and CD90.1 microbeads, encapsulated in alginate hydrogel and then cryopreserved. After thawing, cell viability and Spermatogonial stem cell (SSC) colony diameter were evaluated. After RNA was isolated and cDNA was synthesised, the expression of stemness genes was considered using RT real-time PCR. Finally, spermatogonial stem cells labelled with BrdU were transplanted to busulfan azoospermic mouse models. Lin28a and Sall4 genes were significantly upregulated after cryopreservation in alginate hydrogel. However, cell viability was significantly decreased. The diameter of colonies consisting of spermatogonial stem cells freeze-thawed in alginate microbeads showed no significant difference with fresh spermatogonial stem cells and the control group. The injection of freeze-thawed spermatogonial stem cells encapsulated in alginate hydrogel resulted in spermatogenesis recovery. Alginate mimics the extracellular matrices (ECM) for spermatogonial stem cells; therefore, it can support stemness potential during the cell cryopreservation process and restart spermatogenesis after transplantation. © 2016 Blackwell Verlag GmbH.

Hydrophobic interactions in complexes of antimicrobial peptides with bacterial polysaccharides.

PubMed

Kuo, Hsin H; Chan, Celine; Burrows, Lori L; Deber, Charles M

2007-06-01

Biofilms of Pseudomonas aeruginosa are responsible for chronic lung infections in cystic fibrosis patients, where they are characterized by overproduction of the exopolysaccharide alginate and are recalcitrant to treatment with conventional antibiotics. Cationic antimicrobial peptides (CAPs) are potential alternatives for the treatment of multi-drug-resistant P. aeruginosa. However, alginate in P. aeruginosa biofilms has been proposed to bind these peptides through hydrophobic interactions, consequently reducing their activity [Chan et al., J Biol Chem 2004; 279: 38749-38754]. Here we perform biophysical analyses of the interactions of alginate with a series of novel peptide antibiotics (alpha-CAPs) of prototypic sequence KK-AAAXAAAAAXAAWAAXAAA-KKKK (where X = Phe, Trp or Leu). The hydrophobic interaction interface in alginate was investigated by examining (i) the effects of polysaccharide composition with respect to D-mannuronate and L-guluronate content; (ii) glycan chain length; (iii) alpha-CAP Trp fluorescence; and (iv) 1-anilinonaphthalene-8-sulfonate fluorescence. The results show that, while M and G residues produce equivalent effects, hydrophobic interactions between alginate and alpha-CAPs require a minimal glycan chain length. Peptide interactions with alginate are deduced to be mediated by hydrophobic microdomains comprised of pyranosyl C-H groups that are inducible upon formation of alpha-CAP-alginate complexes due to charge neutralization between the two species.

An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering.

PubMed

Kundu, Joydip; Shim, Jin-Hyung; Jang, Jinah; Kim, Sung-Won; Cho, Dong-Woo

2015-11-01

Regenerative medicine is targeted to improve, restore or replace damaged tissues or organs using a combination of cells, materials and growth factors. Both tissue engineering and developmental biology currently deal with the process of tissue self-assembly and extracellular matrix (ECM) deposition. In this investigation, additive manufacturing (AM) with a multihead deposition system (MHDS) was used to fabricate three-dimensional (3D) cell-printed scaffolds using layer-by-layer (LBL) deposition of polycaprolactone (PCL) and chondrocyte cell-encapsulated alginate hydrogel. Appropriate cell dispensing conditions and optimum alginate concentrations for maintaining cell viability were determined. In vitro cell-based biochemical assays were performed to determine glycosaminoglycans (GAGs), DNA and total collagen contents from different PCL-alginate gel constructs. PCL-alginate gels containing transforming growth factor-β (TGFβ) showed higher ECM formation. The 3D cell-printed scaffolds of PCL-alginate gel were implanted in the dorsal subcutaneous spaces of female nude mice. Histochemical [Alcian blue and haematoxylin and eosin (H&E) staining] and immunohistochemical (type II collagen) analyses of the retrieved implants after 4 weeks revealed enhanced cartilage tissue and type II collagen fibril formation in the PCL-alginate gel (+TGFβ) hybrid scaffold. In conclusion, we present an innovative cell-printed scaffold for cartilage regeneration fabricated by an advanced bioprinting technology. Copyright © 2013 John Wiley & Sons, Ltd.

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

PubMed

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

The synthesis and characterization of hydrogel chitosan-alginate with the addition of plasticizer lauric acid for wound dressing application

NASA Astrophysics Data System (ADS)

Izak Rudyardjo, Djony; Wijayanto, Setiawan

2017-05-01

The writers conducted a study about the synthesis and characterization of hydrogel chitosan-alginate by addition plasticizer lauric acid for wound dressing application. The purpose was to find out the impact of lauric acid concentration variation on hydrogel chitosan-alginate to get the best mechanical and physical properties to be applied as wound dressing in accordance with existing standards. This study used commercially chitosan from extract of shells crab, commercially-available alginate from the extract of sargassum sp, and commercial lauric acid from palm starch. The addition of lauric acid was aimed to repair mechanical properties of hydrogel. The composition of chitosan-alginate is 4:1 (v/v), while the lauric acid concentration variations are 0%, 1%, 2%, 3%, 4%, and 5% w/v. The characterization of mechanical properties test (Tensile strength and Elongation at break) at hydrogel showed the hydrogel chitosan-alginate-lauric acid have the characteristic which meets the standard of mechanical properties for human skin. The best performance of hydrogel chitosan-alginate-lauric acid was obtained by increasing luric acid concentration by 4%, which has a thickness value of 125.46±0.63 µm, elongation 28.89±1.01 %, tensile strength (9.01±0.65) MPa, and ability to absorb liquids (601.45 ±1.24) %.

A computational modeling approach for the characterization of mechanical properties of 3D alginate tissue scaffolds.

PubMed

Nair, K; Yan, K C; Sun, W

2008-01-01

Scaffold guided tissue engineering is an innovative approach wherein cells are seeded onto biocompatible and biodegradable materials to form 3-dimensional (3D) constructs that, when implanted in the body facilitate the regeneration of tissue. Tissue scaffolds act as artificial extracellular matrix providing the environment conducive for tissue growth. Characterization of scaffold properties is necessary to understand better the underlying processes involved in controlling cell behavior and formation of functional tissue. We report a computational modeling approach to characterize mechanical properties of 3D gellike biomaterial, specifically, 3D alginate scaffold encapsulated with cells. Alginate inherent nonlinearity and variations arising from minute changes in its concentration and viscosity make experimental evaluation of its mechanical properties a challenging and time consuming task. We developed an in silico model to determine the stress-strain relationship of alginate based scaffolds from experimental data. In particular, we compared the Ogden hyperelastic model to other hyperelastic material models and determined that this model was the most suitable to characterize the nonlinear behavior of alginate. We further propose a mathematical model that represents the alginate material constants in Ogden model as a function of concentrations and viscosity. This study demonstrates the model capability to predict mechanical properties of 3D alginate scaffolds.

Hydrocolloid liquid-core capsules for the removal of heavy-metal cations from water.

PubMed

Nussinovitch, A; Dagan, O

2015-12-15

Liquid-core capsules with a non-crosslinked alginate fluidic core surrounded by a gellan membrane were produced in a single step to investigate their ability to adsorb heavy metal cations. The liquid-core gellan-alginate capsules, produced by dropping alginate solution with magnesium cations into gellan solution, were extremely efficient at adsorbing lead cations (267 mg Pb(2+)/g dry alginate) at 25 °C and pH 5.5. However, these capsules were very weak and brittle, and an external strengthening capsule was added by using magnesium cations. The membrane was then thinned with the surfactant lecithin, producing capsules with better adsorption attributes (316 mg Pb(+2)/g dry alginate vs. 267 mg Pb(+2)/g dry alginate without lecithin), most likely due to the thinner membrane and enhanced mass transfer. The capsules' ability to adsorb other heavy-metal cations - copper (Cu(2+)), cadmium (Cd(2+)) and nickel (Ni(2+)) - was tested. Adsorption efficiencies were 219, 197 and 65 mg/g, respectively, and were correlated with the cation's affinity to alginate. Capsules with the sorbed heavy metals were regenerated by placing in a 1M nitric acid suspension for 24h. Capsules could undergo three regeneration cycles before becoming damaged. Copyright © 2015 Elsevier B.V. All rights reserved.

RBC Storage Effect on Coagulation, Microparticles and Microchimerism in Critically Ill Patients

DTIC Science & Technology

2015-03-01

Award Number: W81XWH-11-2-0028 TITLE: “RBC Storage Effect on Coagulation, Microparticles and Microchimerism in Critically Ill Patients...27 DEC 2010 - 26 DEC 2015 – 4. TITLE AND SUBTITLE "“RBC Storage Effect on Coagulation, Microparticles and 5a. CONTRACT NUMBER Microchimerism in...15. SUBJECT TERMS RBC storage age; microchimerism; critically ill patients; coagulation; microparticles 16. SECURITY CLASSIFICATION OF: U 17

Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

PubMed Central

Serda, Rita E.; Blanco, Elvin; Mack, Aaron; Stafford, Susan J.; Amra, Sarah; Li, Qingpo; van de Ven, Anne L.; Tanaka, Takemi; Torchilin, Vladimir P.; Wiktorowicz, John E.; Ferrari, Mauro

2014-01-01

Mass transport of drug delivery vehicles is guided by particle properties, such as shape, composition and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light chain variable region, fibrinogen, and complement component 1 compared to their anionic counterparts. The anionic-surface favored equal accumulation of microparticles in the liver and spleen, while cationic-surfaces favored preferential accumulation in the spleen. Immunohistochemistry supported macrophage internalization of both anionic and cationic silicon microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution. PMID:21303614

Controlled release of an extract of Calendula officinalis flowers from a system based on the incorporation of gelatin-collagen microparticles into collagen I scaffolds: design and in vitro performance.

PubMed

Jiménez, Ronald A; Millán, Diana; Suesca, Edward; Sosnik, Alejandro; Fontanilla, Marta R

2015-06-01

Aiming to develop biological skin dresses with improved performance in the treatment of skin wounds, acellular collagen I scaffolds were modified with polymeric microparticles and the subsequent loading of a hydroglycolic extract of Calendula officinalis flowers. Microparticles made of gelatin-collagen were produced by a water-in-oil emulsion/cross-linking method. Thereafter, these microparticles were mixed with collagen suspensions at three increasing concentrations and the resulting mixtures lyophilized to make microparticle-loaded porous collagen scaffolds. Resistance to enzymatic degradation, ability to associate with the C. officinalis extract, and the extract release profile of the three gelatin-collagen microparticle-scaffold prototypes were assessed in vitro and compared to collagen scaffolds without microparticles used as control. Data indicated that the incorporation of gelatin-collagen microparticles increased the resistance of the scaffolds to in vitro enzymatic degradation, as well as their association with the C. officinalis flower extract. In addition, a sharp decrease in cytotoxicity, as well as more prolonged release of the extract, was attained. Overall results support the potential of these systems to develop innovative dermal substitutes with improved features. Furthermore, the gelatin-collagen mixture represents a low-cost and scalable alternative with high clinical transferability, especially appealing in developing countries.

Skin penetration and photoprotection of topical formulations containing benzophenone-3 solid lipid microparticles prepared by the solvent-free spray-congealing technique.

PubMed

Martins, Rodrigo Molina; Siqueira, Silvia; Fonseca, Maria José Vieira; Freitas, Luis Alexandre Pedro

2014-01-01

Solid-lipid microparticles loaded with high amounts of the sunscreen UV filter benzophenone-3 were prepared by spray congealing with the objective of decreasing its skin penetration and evaluate whether the sunscreen's photoprotection were impaired by the microencapsulation process. The microparticles were produced using the natural lipids carnauba wax or bees wax and three different concentrations of benzophenone-3 (30, 50 and 70%) using spray congealing technique. The microparticles presented properties suitable for topical application, such as spherical morphology, high encapsulation efficiency (95.53-102.2%), average particle sizes between 28.5 and 60.0 µm with polydispersivities from 1.2 to 2.5. In studies of in vitro skin penetration and preliminary stability, formulations of gel cream containing carnauba wax solid lipid microparticles and 70% benzophenone-3 when compared to the formulation added of bees wax solid-lipid microparticles containing 70% benzophenone-3, was stable considering the several parameters evaluated and were able to decrease the penetration of the UV filter into pig skin. Moreover, the formulations containing solid lipid microparticles with 70% benzophenone-3 increased the photoprotective capacity of benzophenone-3 under UV irradiation. The results show that spray-congealed microparticles are interesting solid forms to decrease the penetration solar filters in the skin without compromising their photoprotection.