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1.
AAPS PharmSciTech ; 22(4): 149, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961149

RESUMO

Parkinson's disease (PD) is the second most common neurological disorder, associated with decreased dopamine levels in the brain. The goal of this study was to assess the potential of a regenerative medicine-based cell therapy approach to increase dopamine levels. In this study, we used rat adrenal pheochromocytoma (PC12) cells that can produce, store, and secrete dopamine. These cells were microencapsulated in the selectively permeable polymer membrane to protect them from immune responses. For fabrication of the microcapsules, we used a modified Buchi spray dryer B-190 that allows for fast manufacturing of microcapsules and is industrially scalable. Size optimization of the microcapsules was performed by systematically varying key parameters of the spraying device. The short- and long-term stabilities of the microcapsules were assessed. In the in vitro study, the cells were found viable for a period of 30 days. Selective permeability of the microcapsules was confirmed via dopamine release assay and micro BCA protein assay. We found that the microcapsules were permeable to the small molecules including dopamine and were impermeable to the large molecules like BSA. Thus, they can provide the protection to the encapsulated cells from the immune cells. Griess's assay confirmed the non-immunogenicity of the microcapsules. These results demonstrate the effective fabrication of microcapsules encapsulating cells using an industrially scalable device. The microcapsules were stable, and the cells were viable inside the microcapsules and were found to release dopamine. Thus, these microcapsules have the potential to serve as the alternative or complementary treatment approach for PD.


Assuntos
Compostos de Alumínio/síntese química , Cápsulas/síntese química , Encapsulamento de Células/métodos , Terapia Baseada em Transplante de Células e Tecidos/métodos , Doença de Parkinson , Compostos de Sódio/síntese química , Compostos de Alumínio/administração & dosagem , Compostos de Alumínio/metabolismo , Animais , Encéfalo/metabolismo , Cápsulas/administração & dosagem , Cápsulas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Dopamina/metabolismo , Camundongos , Células PC12 , Doença de Parkinson/metabolismo , Doença de Parkinson/terapia , Polímeros/administração & dosagem , Polímeros/síntese química , Polímeros/metabolismo , Estudos Prospectivos , Células RAW 264.7 , Ratos , Compostos de Sódio/administração & dosagem , Compostos de Sódio/metabolismo , Resultado do Tratamento
2.
Macromol Rapid Commun ; 41(7): e1900654, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32134544

RESUMO

The development of polymers with built-in sensors that provide readily perceptible optical warning signs of mechanical events has received considerable interest. A simple and versatile concept to bestow polymers with mechanochromic behavior is the incorporation of dye-filled microcapsules. Such capsules release their cargo when their shell is damaged, and the dye is subsequently activated through a chemical or physical change that causes a chromogenic response. Here, we report the preparation of fluorescent poly(urea-formaldehyde) microcapsules containing solutions of a solvatochromic cyanostilbene dye and their integration in different polymers. When objects made from such composites are damaged, the dye solution is released from the containers, diffuses into the matrix, and the solvent evaporates. As a result, the polarity around the dye molecules changes, and this leads to a change of the fluorescence color. Alternatively, the dye is blended into the polymer matrix, microcapsules are loaded with a solvent, and the release of the latter triggers the color change. Both mechanisms afford ratiometric signals because the capsules that remain intact or dye molecules that are not exposed to the solvent can be used as a built-in reference; therefore, a quantitative assessment of the damage inflicted on the material is a priori possible.


Assuntos
Corantes Fluorescentes/química , Formaldeído/química , Polímeros/química , Ureia/química , Cápsulas/síntese química , Cápsulas/química , Corantes Fluorescentes/síntese química , Formaldeído/síntese química , Fenômenos Mecânicos , Estrutura Molecular , Tamanho da Partícula , Polímeros/síntese química , Ureia/síntese química
3.
Proc Natl Acad Sci U S A ; 114(32): 8475-8480, 2017 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-28739948

RESUMO

Biological quorum sensing refers to the ability of cells to gauge their population density and collectively initiate a new behavior once a critical density is reached. Designing synthetic materials systems that exhibit quorum sensing-like behavior could enable the fabrication of devices with both self-recognition and self-regulating functionality. Herein, we develop models for a colony of synthetic microcapsules that communicate by producing and releasing signaling molecules. Production of the chemicals is regulated by a biomimetic negative feedback loop, the "repressilator" network. Through theory and simulation, we show that the chemical behavior of such capsules is sensitive to both the density and number of capsules in the colony. For example, decreasing the spacing between a fixed number of capsules can trigger a transition in chemical activity from the steady, repressed state to large-amplitude oscillations in chemical production. Alternatively, for a fixed density, an increase in the number of capsules in the colony can also promote a transition into the oscillatory state. This configuration-dependent behavior of the capsule colony exemplifies quorum-sensing behavior. Using our theoretical model, we predict the transitions from the steady state to oscillatory behavior as a function of the colony size and capsule density.


Assuntos
Biomimética/métodos , Cápsulas/síntese química , Percepção de Quorum/fisiologia , Cápsulas/farmacologia , Simulação por Computador , Retroalimentação , Modelos Teóricos , Células Procarióticas , Transdução de Sinais
4.
J Microencapsul ; 36(4): 410-419, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31269832

RESUMO

Poly(urea-formaldehyde) (PUF) microcapsules filled with dicyclopentadiene (DCPD) were prepared by in situ polymerisation and the effect of synthesis parameters, such as pH of the solution and agitation rate, on microcapsules size and shell thickness was evaluated. Scanning electron microscopy (SEM) and Fourier transform infra-red spectroscopy (FTIR) were performed. Adjusted pH conditions (pH = 3.5) and agitation rate (1350 RPM) were found using a design of experiments (DOE). SEM results indicated that microcapsule size was directly affected by agitation rate, whereas shell thickness was mostly affected by pH. After obtaining adjusted synthesis conditions, microcapsules presenting mean size of 60 µm and mean shell thickness of 4 µm were embedded in an epoxy matrix for evaluating the self-healing effect. FTIR and SEM analyses in damaged samples suggested that a healing agent was delivered to the crack location.


Assuntos
Cápsulas/síntese química , Formaldeído/síntese química , Polímeros/síntese química , Cápsulas/química , Técnicas de Química Sintética , Composição de Medicamentos , Formaldeído/química , Concentração de Íons de Hidrogênio , Indenos/administração & dosagem , Tamanho da Partícula , Polimerização , Polímeros/química
5.
Molecules ; 24(5)2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845646

RESUMO

Microencapsulated phase change materials (MicroPCMs)-incorporated in epoxy composites have drawn increasing interest due to their promising application potential in the fields of thermal energy storage and temperature regulation. However, the study on the effect of MicroPCMs on their microstructure, thermal and viscoelastic properties is quite limited. Herein, a new type of smart epoxy composite incorporated with polyurea (PU)-shelled MicroPCMs was fabricated via solution casting method. Field emission-scanning electron microscope (FE-SEM) images revealed that the MicroPCMs were uniformly distributed in the epoxy matrix. The thermal stabilities, conductivities, phase change properties, and dynamic mechanical behaviors of the composite were studied by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), thermal constant analyzer and infrared thermography. The results suggested that the heat storage ability of the composites was improved by increasing the MicroPCMs content. The thermal stability of MicroPCMs was found to be enhanced after incorporation into the matrix, and the MicroPCMs-incorporated epoxy composites showed a good thermal cycling reliability. Moreover, the incorporation of MicroPCMs reduced the composites' storage modulus but increased the glass transition temperature (Tg) as a result of their restriction to the chain motion of epoxy resin. Besides, a less marked heating effect for the composite was explored through infrared thermography analysis, demonstrating the good prospect for temperature regulation application.


Assuntos
Cápsulas/síntese química , Resinas Epóxi/química , Transição de Fase , Alcanos/química , Emulsões/química , Temperatura Alta , Cinética , Teste de Materiais/métodos , Fenômenos Mecânicos , Tamanho da Partícula , Reprodutibilidade dos Testes , Propriedades de Superfície , Temperatura , Termodinâmica
6.
Molecules ; 24(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018491

RESUMO

This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD (0.0625-1 mg/mL) showed a higher antioxidant activity than that of both individuals. A possible intermolecular interaction between ANC and FA-g-MD was studied by UV-vis spectra. Intracellular reactive oxygen species (ROS), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, and protein expression of quinone oxidoreductase 1(NQO1), glutathione reductase (GSR) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured through human colon cancer cells (HT-29). After a 24-hour incubation of the HT-29, the combinations (0-60 µg/mL) exhibited a high potential to diminish the ROS level. And the distinct upregulated expressions of GCLC and NQO1 of HT-29 were detected after treatment with combinations compared to those of single ones. These results suggested that the ANC-FA-g-MD microcapsules exerts enhanced antioxidant effect with capability of the modulation of GCLC and NQO1.


Assuntos
Antocianinas/farmacologia , Cápsulas/síntese química , Ácidos Cumáricos/química , Portadores de Fármacos , Sequestradores de Radicais Livres/farmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Polissacarídeos/química , Antocianinas/química , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Ativação Enzimática/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa Redutase/genética , Glutationa Redutase/metabolismo , Células HT29 , Humanos , Peróxido de Hidrogênio/farmacologia , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Subunidades Proteicas/agonistas , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo
7.
Biomacromolecules ; 19(9): 3883-3893, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30088918

RESUMO

Microcapsules and nanocapsules based on the contemporary presence of sulfonate lignin and tannic acid have been prepared by the layer-by-layer procedure, using MnCO3 or organosolv lignin as core templates, and polydiallyldimethylammonium chloride or chitosan as positive charged supporting layers. Nanocapsules and microcapsules of mixed polyphenols showed antioxidant activity, UV-shielding properties, and electrochemical responsiveness, higher than that in homopolymer nanocapsule counterparts and of the native polyphenols, suggesting the presence of synergistic effects between the two components. The presence of UV-visible bathochromic shift suggested the formation of J-aggregates characterized by an orientation of the adjacent phenolic rings parallel to the longitudinal direction of the layer, with a head-to-tail like arrangement. Moreover, nanocapsules of mixed polyphenols showed an aggregation state higher than that observed in references, the specific morphology of their surface being dependent on the structural arrangement of the different components.


Assuntos
Antioxidantes/administração & dosagem , Cápsulas/química , Nanocápsulas/química , Protetores contra Radiação/administração & dosagem , Cápsulas/síntese química , Radicais Livres/química , Lignina/química , Polifenóis/química , Taninos/química , Raios Ultravioleta
8.
J Labelled Comp Radiopharm ; 61(6): 472-486, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29380410

RESUMO

Internal therapy with α-emitters should be well suited for micrometastatic disease. Radium-224 emits multiple α-particles through its decay and has a convenient 3.6 days of half-life. Despite its attractive properties, the use of 224 Ra has been limited to bone-seeking applications because it cannot be stably bound to a targeting molecule. Alternative delivery systems for 224 Ra are therefore of considerable interest. In this study, calcium carbonate microparticles are proposed as carriers for 224 Ra, designed for local therapy of disseminated cancers in cavitary regions, such as peritoneal carcinomatosis. Calcium carbonate microparticles were radiolabeled by precipitation of 224 Ra on the particle surface, resulting in high labeling efficiencies for both 224 Ra and daughter 212 Pb and retention of more than 95% of these nuclides for up to 1 week in vitro. The biodistribution after intraperitoneal administration of the 224 Ra-labeled CaCO3 microparticles in immunodeficient mice revealed that the radioactivity mainly remained in the peritoneal cavity. In addition, the systemic distribution of 224 Ra was found to be strongly dependent on the amount of administered microparticles, with a reduced skeletal uptake of 224 Ra with increasing dose. The results altogether suggest that the 224 Ra-labeled CaCO3 microparticles have promising properties for use as a localized internal α-therapy of cavitary cancers.


Assuntos
Carbonato de Cálcio/química , Cápsulas/síntese química , Compostos Radiofarmacêuticos/síntese química , Radioterapia/métodos , Rádio (Elemento)/uso terapêutico , Tório/uso terapêutico , Animais , Cápsulas/farmacocinética , Cápsulas/uso terapêutico , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/administração & dosagem , Tório/administração & dosagem , Distribuição Tecidual
9.
Int J Mol Sci ; 19(3)2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29538323

RESUMO

Controllable pesticide release in response to environmental stimuli is highly desirable for better efficacy and fewer adverse effects. Combining the merits of natural and synthetic polymers, pH and temperature dual-responsive chitosan copolymer (CS-g-PDMAEMA) was facilely prepared through free radical graft copolymerization with 2-(dimethylamino) ethyl 2-methacrylate (DMAEMA) as the vinyl monomer. An emulsion chemical cross-linking method was used to expediently fabricate pyraclostrobin microcapsules in situ entrapping the pesticide. The loading content and encapsulation efficiency were 18.79% and 64.51%, respectively. The pyraclostrobin-loaded microcapsules showed pH-and thermo responsive release. Microcapsulation can address the inherent limitation of pyraclostrobin that is photo unstable and highly toxic on aquatic organisms. Compared to free pyraclostrobin, microcapsulation could dramatically improve its photostability under ultraviolet light irradiation. Lower acute toxicity against zebra fish on the first day and gradually similar toxicity over time with that of pyraclostrobin technical concentrate were in accordance with the release profiles of pyraclostrobin microcapsules. This stimuli-responsive pesticide delivery system may find promising application potential in sustainable plant protection.


Assuntos
Cápsulas/síntese química , Quitosana/química , Metacrilatos/química , Nylons/química , Praguicidas/farmacocinética , Estrobilurinas/farmacocinética , Animais , Cápsulas/efeitos da radiação , Liberação Controlada de Fármacos , Praguicidas/toxicidade , Estrobilurinas/toxicidade , Raios Ultravioleta , Peixe-Zebra
10.
Molecules ; 23(5)2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735955

RESUMO

The xanthine oxidase inhibitory activity and thermostability of Cinnamomum osmophloeum leaf oil microencapsulated with ß-cyclodextrin were evaluated in this study. The yield of leaf oil microcapsules was 86.3% using the optimal reaction conditions at the leaf oil to ß-cyclodextrin ratio of 15:85 and ethanol to water ratio ranging from 1:3 to 1:5. Based on the FTIR analysis, the characteristic absorption bands of major constituent, trans-cinnamaldehyde, were confirmed in the spectra of leaf oil microcapsules. According to the dry-heat aging test, ß-cyclodextrin was thermostable under the high temperature conditions, and it was beneficial to reduce the emission of C. osmophloeum leaf oil. Leaf oil microcapsules exhibited high xanthine oxidase inhibitory activity, with an IC50 value of 83.3 µg/mL. It is concluded that the lifetime of C. osmophloeum leaf oil can be effectively improved by microencapsulation, and leaf oil microcapsules possess superior xanthine oxidase inhibitory activity.


Assuntos
Acroleína/análogos & derivados , Cinnamomum/química , Supressores da Gota/química , Óleos de Plantas/química , Xantina Oxidase/antagonistas & inibidores , beta-Ciclodextrinas/química , Acroleína/química , Acroleína/isolamento & purificação , Cápsulas/síntese química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Ensaios Enzimáticos , Supressores da Gota/isolamento & purificação , Temperatura Alta , Humanos , Folhas de Planta/química , Óleos de Plantas/isolamento & purificação , Xantina Oxidase/química
11.
Bioconjug Chem ; 28(7): 1859-1866, 2017 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-28548819

RESUMO

Particle-cell interactions are governed by, among other factors, the composition and surface properties of the particles. Herein, we report the preparation of various polymer capsules with different compositions and properties via atom transfer radical polymerization mediated continuous assembly of polymers (CAPATRP), where the cellular interactions of these capsules, particularly fouling and specific targeting, are examined by flow cytometry and deconvolution microscopy. Acrylated eight-arm poly(ethylene glycol) (8-PEG) and poly(N-(2-hydroxypropyl)-methacrylamide) (PHPMA) as well as methacrylated hyaluronic acid (HA), poly(glutamic acid) (PGA), and poly(methacrylic acid) (PMA) are used as macro-cross-linkers to obtain a range of polymer capsules with different compositions (PEG, PHPMA, HA, PGA, and PMA). Capsules composed of low-fouling polymers, PEG and PHPMA, show negligible association with macrophage Raw 264.7, monocyte THP-1, and HeLa cells. HA capsules, although moderately low-fouling (<22%) to HeLa, BT474, Raw 264.7, and THP-1 cells, exhibit high targeting specificity to CD44-over-expressing MDA-MB-231 cells. In contrast, PGA and PMA capsules show high cellular association toward phagocytic Raw 264.7 and THP-1 cells. These findings demonstrate the capability of the CAPATRP technique in preparing polymer capsules with specific cellular interactions.


Assuntos
Membrana Celular/metabolismo , Polímeros/química , Animais , Cápsulas/síntese química , Cápsulas/química , Cápsulas/metabolismo , Reagentes de Ligações Cruzadas/química , Citometria de Fluxo , Células HeLa , Humanos , Camundongos , Microscopia , Polímeros/síntese química , Polímeros/metabolismo , Células RAW 264.7 , Propriedades de Superfície
12.
Biotechnol Bioeng ; 114(12): 2920-2930, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28782793

RESUMO

Up to present, many advantages have been achieved in the field of cell-based therapies by applying sophisticated methodologies and delivery approaches. Microcapsules are capable to provide safe microenvironment for cells during transplantation in a simulated physiological 3D milieu. Here, we aimed to investigate the effect of alginate-gelatin encapsulation on angiogenic behavior of human endothelial cells over a period of 5 days. Human umbilical vein endothelial cells were encapsulated by alginate-gelatin substrate and incubated for 5 days. MTT and autophagy PCR array analysis were used to monitor cell survival rate. For in vitro angiogenesis analysis, cell distribution of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were detected by ELISA. In addition to in vitro tubulogenesis assay, we monitored the expression of VE-cadherin by Western blotting. The migration capacity of encapsulated HUVECs was studied by measuring MMP-2 and MMP-9 via gelatin zymography. The in vivo angiogenic potential of encapsulated HUVECs was analyzed in immune-compromised mouse implant model during 7 days post-transplantation. We demonstrated that encapsulation promoted HUVECs cell survival and proliferation. Compared to control, no significant differences were observed in autophagic status of encapsulated cells (p > 0.05). The level of Tie-1, Tie-2, VEGFR-1, and VEGFR-2 were increased, but did not reach to significant levels. Encapsulation decreased MMP-2, -9 activity and increased the VE-cadherin level in enclosed cells (p < 0.05). Moreover, an enhanced in vivo angiogenic response of encapsulated HUVECs was evident as compared to non-capsulated cells (p < 0.05). These observations suggest that alginate-gelatin encapsulation can induce angiogenic response in in vivo and in vitro conditions.


Assuntos
Alginatos/química , Prótese Vascular , Células Endoteliais/citologia , Células Endoteliais/fisiologia , Gelatina/química , Neovascularização Fisiológica/fisiologia , Alicerces Teciduais , Animais , Cápsulas/síntese química , Células Cultivadas , Materiais Revestidos Biocompatíveis/síntese química , Células Endoteliais/transplante , Desenho de Equipamento , Análise de Falha de Equipamento , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Humanos , Técnicas In Vitro , Camundongos
13.
Biomacromolecules ; 18(7): 2064-2072, 2017 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-28511539

RESUMO

Self-assembly of native glycinin at room temperature was investigated as a function of the pH and the NaCl concentration. Microphase separation leading to the formation of dense protein microdomains was observed by confocal laser scanning microscopy. Depending on the conditions, the microdomains coalesced into a continuous protein rich phase or associated into large clusters. Addition of ß-conglycinin inhibited phase separation and reduced the pH range in which it occurred. Microdomains of glycinin that were formed in the presence of 0.1 M NaCl transformed into hollow stable cross-linked microcapsules when heated above 60 °C with diameters between 3 and 30 µm depending on the protein concentration and a shell thickness between 1.0 and 1.4 µm. The microcapsules were stable to dilution in salt free water, whereas microdomains formed at room temperature redispersed. Microdomains formed in mixtures with ß-conglycinin did not transform into microcapsules, but they became stable cross-linked homogeneous microgels.


Assuntos
Cápsulas , Globulinas/química , Cloreto de Sódio/química , Proteínas de Soja/química , Cápsulas/síntese química , Cápsulas/química , Tamanho da Partícula
14.
J Mater Sci Mater Med ; 28(7): 99, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28534282

RESUMO

Modified supersaturated phosphate buffer solutions were used to synthesize phosphate-based spheres, including calcium phosphate (CaP), strontium phosphate (SrP) and barium phosphate (BaP). A series of ions concentrations in the modified phosphate buffer solutions were investigated in order to study their effects in precipitates morphologies. During synthesis, it was found that magnesium was the key factor in sphere formation. The morphologies of calcium phosphate, strontium phosphate and barium phosphate precipitates varied as the concentration of magnesium ions varied. When sufficient magnesium was provided, the precipitates appeared spherical, and the diameter was in range of 0.5-2 µm. The morphologies, compositions and structure of spheres were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and N2 adsorption analysis. Moreover, the application of magnesium substituted calcium phosphate spheres in dentin tubules occlusion was investigated.


Assuntos
Fosfatos de Cálcio/química , Cápsulas/síntese química , Cápsulas/isolamento & purificação , Precipitação Química , Composição de Medicamentos/métodos , Microesferas , Soluções Tampão , Tamanho da Partícula , Soluções/química
15.
Biotechnol Bioeng ; 113(11): 2485-95, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27159557

RESUMO

Islet transplantation is a potential cure for diabetic patients, however this procedure is not widely adopted due to the high rate of graft failure. Islet encapsulation within hydrogels is employed to provide a three-dimensional microenvironment conducive to survival of transplanted islets to extend graft function. Herein, we present a novel macroencapsulation device, composed of PEG hydrogel, that combines encapsulation with lithography techniques to generate polydimethylsiloxane (PDMS) molds. PEG solutions are mixed with islets, which are then cast into PDMS molds for subsequent crosslinking. The molds can also be employed to provide complex architectures, such as microchannels that may allow vascular ingrowth through pre-defined regions of the hydrogel. PDMS molds allowed for the formation of stable gels with encapsulation of islets, and in complex architectures. Hydrogel devices with a thickness of 600 µm containing 500 islets promoted normoglycemia within 12 days following transplantation into the epididymal fat pad, which was sustained over the two-month period of study until removal of the device. The inclusion of microchannels, which had a similar minimum distance between islets and the hydrogel surface, similarly promoted normoglycemia. A glucose challenge test indicated hydrogel devices achieved normoglycemia 90 min post-dextrose injections, similar to control mice with native pancreata. Histochemical staining revealed that transplanted islets, identified as insulin positive, were viable and isolated from host tissue at 8 weeks post-transplantation, yet devices with microchannels had tissue and vascular ingrowth within the channels. Taken together, these results demonstrate a system for creating non-degradable hydrogels with complex geometries for encapsulating islets capable of restoring normoglycemia, which may expand islet transplantation as a treatment option for diabetic patients. Biotechnol. Bioeng. 2016;113: 2485-2495. © 2016 Wiley Periodicals, Inc.


Assuntos
Cápsulas/síntese química , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Hidrogéis/química , Transplante das Ilhotas Pancreáticas/instrumentação , Ilhotas Pancreáticas/citologia , Implantes Absorvíveis , Animais , Sobrevivência Celular , Células Cultivadas , Desenho de Equipamento , Análise de Falha de Equipamento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento
16.
Biotechnol Bioeng ; 112(6): 1092-101, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25580912

RESUMO

Enzyme encapsulation is a simple, gentle, and general method for immobilizing enzyme, but it often suffers from one or more problems regarding enzyme loading efficiency, enzyme leakage, mechanical stability, and recyclability. Here we report a novel, simple, and efficient method for enzyme encapsulation to overcome these problems by forming stable organic-inorganic hybrid capsules. A new, facile, one-step, and template-free synthesis of organic-inorganic capsules in aqueous phase were developed based on PEI-induced simultaneous interfacial self-assembly of Fmoc-FF and polycondensation of silicate. Addition of an aqueous solution of Fmoc-FF and sodium silicate into an aqueous solution of PEI gave a new class of organic-inorganic hybrid capsules (FPSi) with multi-layered structure in high yield. The capsules are mechanically stable due to the incorporation of inorganic silica. Direct encapsulation of enzyme such as epoxide hydrolase SpEH and BSA along with the formation of the organic-inorganic capsules gave high yield of enzyme-containing capsules (∼1.2 mm in diameter), >90% enzyme loading efficiency, high specific enzyme loading (158 mg protein g(-1) carrier), and low enzyme leakage (<3% after 48 h incubation). FPSi-SpEH capsules catalyzed the hydrolysis of cyclohexene oxide to give (1R, 2R)-cyclohexane-1,2-diol in high yield and concentration, with high specific activity (6.94 U mg(-1) protein) and the same high enantioselectivity as the free enzyme. The immobilized SpEH demonstrated also excellent operational stability and recyclability: retaining 87% productivity after 20 cycles with a total reaction time of 80 h. The new enzyme encapsulation method is efficient, practical, and also better than other reported encapsulation methods.


Assuntos
Cápsulas/síntese química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Epóxido Hidrolases/química , Epóxido Hidrolases/metabolismo , Cicloexenos/metabolismo , Estabilidade Enzimática , Fluorenos/química , Hidrólise , Polietilenoimina/química , Silicatos/química
17.
Langmuir ; 31(33): 9228-35, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26244815

RESUMO

We report a simple approach to fabricate custom-shape microcapsules using hydrogel templates synthesized by stop flow lithography. Cargo-containing microcapsules were made by coating hydrogel particles with a single layer of poly-l-lysine followed by a one-step core degradation and capsule cross-linking procedure. We determined appropriate coating conditions by investigating the effect of pH, ionic strength, and prepolymer composition on the diffusion of polyelectrolytes into the oppositely charged hydrogel template. We also characterized the degradation of the templating core by tracking the diffusivity of nanoparticles embedded within the hydrogel. Unlike any other technique, this approach allows for easy fabrication of microcapsules with internal features (e.g., toroids) and selective surface modification of Janus particles using any polyelectrolyte. These soft, flexible capsules may be useful for therapeutic applications as well as fundamental studies of membrane mechanics.


Assuntos
Cápsulas/química , Cápsulas/síntese química , Hidrogéis/química , Nanosferas/química
18.
J Mater Sci Mater Med ; 26(2): 61, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25631263

RESUMO

Microparticles of Celecoxib, dispersed in a matrix of poly(lactic-co-glycolic acid) (PLGA), were prepared by electrospraying using different solvent mixtures to investigate the influence upon particle formation and the resulting particle characteristics. Mixtures consisting of a good solvent, acetone, and an anti-solvent, methanol, for PLGA were studied in different ratios. Properties of the spraying solutions were examined and the resulting microparticles were characterized with regard to size, morphology, porosity, solid state form, surface chemistry and drug release. Particle formation was strongly influenced by the polymer molecular conformation during droplet formation and by the anti-solvent concentration during droplet drying. A strong correlation was found between particle morphology and the solubility of the polymer in the solvent mixtures. The lack of chain entanglements in droplets containing anti-solvent resulted in compact polymer conformation and grain-like particle morphology. Further, the early precipitation of polymer and low chain interaction with increasing content of anti-solvent resulted in surface enrichment of drug (from 10 and 20% up to 41 and 57% respectively), also demonstrated by the increasingly higher drug release rates. The results demonstrate the importance of solvent composition in particle preparation and indicate potential for exploiting this dependence to improve pharmaceutical particle design and performance.


Assuntos
Cápsulas/síntese química , Composição de Medicamentos/métodos , Galvanoplastia/métodos , Ácido Láctico/química , Ácido Poliglicólico/química , Pirazóis/química , Solventes/química , Sulfonamidas/química , Celecoxib , Misturas Complexas/química , Difusão , Teste de Materiais , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Propriedades de Superfície
19.
J Mater Sci Mater Med ; 26(4): 166, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25791461

RESUMO

Hydroxyapatite (HA) has been investigated as a delivery system for antimicrobial and antibacterial agents to simultaneously stimulate bone regeneration and prevent infection. Despite evidence supporting the bactericidal efficiency of these HA carriers, few studies have focused on the effect of this association on bone regeneration. In this work, we evaluated the physico-chemical properties of hydroxyapatite microspheres loaded with chlorhexidine (CHX) at two different concentrations, 0.9 and 9.1 µgCHX/cm2 HA, and characterized their effects on in vitro osteoblast viability and bone regeneration. Ultraviolet-visible spectroscopy, scanning and transmission electron microscopy associated with energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy were used to characterize the association of CHX and HA nanoparticles. The high CHX loading dose induced formation of organic CHX plate-like aggregates on the HA surface, whereas a Langmuir film was formed at the low CHX surface concentration. Quantitative evaluation of murine osteoblast viability parameters, including adhesion, mitochondrial activity and membrane integrity of cells exposed to HA/CHX extracts, revealed a cytotoxic effect for both loading concentrations. Histomorphological analysis upon implantation into the dorsal connective tissues and calvaria of rats for 7 and 42 days showed that the high CHX concentration induced the infiltration of inflammatory cells, resulting in retarded bone growth. Despite a strong decrease in in vitro cell viability, the low CHX loading dose did not impair the biocompatibility and osteoconductivity of HA during bone repair. These results indicate that high antimicrobial doses may activate a strong local inflammatory response and disrupt the long-term osteoconductive properties of CHX-HA delivery systems.


Assuntos
Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Substitutos Ósseos/administração & dosagem , Clorexidina/administração & dosagem , Implantes de Medicamento/administração & dosagem , Osteoblastos/fisiologia , Osteogênese/fisiologia , Células 3T3 , Animais , Antibacterianos/administração & dosagem , Antibacterianos/química , Substitutos Ósseos/síntese química , Cápsulas/administração & dosagem , Cápsulas/síntese química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Clorexidina/química , Terapia Combinada , Difusão , Implantes de Medicamento/química , Durapatita/administração & dosagem , Durapatita/química , Masculino , Camundongos , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Ratos , Ratos Wistar
20.
Bioprocess Biosyst Eng ; 38(2): 329-39, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25168123

RESUMO

Bacillus thuringiensis (Bt) is one of the bioinsecticides used worldwide due to its specific toxicity against target pests in their larval stage. Despite this advantage, its use is limited because of their short persistence in field when exposed to ultra violet light and changing environmental conditions. In this work, microencapsulation has been evaluated as a promising method to improve Bt activity. The objective of this study was to develop and characterize native and modified amaranth starch granules and evaluate their potential application as wall materials in the microcapsulation of B thuringiensis serovar kurstaki HD-1 (Bt- HD1), produced by spray drying. Native amaranth starch granules were treated by hydrolyzation, high energy milling (HEM) and were chemically modified by phosphorylation and succinylation. The size of the Bt microcapsules varied from 12.99 to 17.14 µm adequate to protect the spores of Bt from ultraviolet radiation. The aw coefficient of the microcapsules produced by the modified starches after drying was low (0.14-1.88), which prevent microbial growth. Microcapsules prepared with phosphorylated amaranth starch presented the highest bacterial count and active material yield. Different concentrations of the encapsulated Bt formulation in phosphorylated amaranth starch showed a high level of insecticidal activity when tested on M. sexta larvae and has great potential to be developed as a bioinsecticide formulation, also, the level of toxicity is much higher than that found in some of the products commercially available.


Assuntos
Amaranthus/química , Bacillus thuringiensis/fisiologia , Cápsulas/síntese química , Controle Biológico de Vetores/métodos , Esporos Bacterianos/fisiologia , Amido/química , Bacillus thuringiensis/química , Proliferação de Células/fisiologia , Teste de Materiais , Esporos Bacterianos/química
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