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1.
Nat Commun ; 11(1): 4907, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999289

RESUMO

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.


Assuntos
Materiais Biomiméticos/administração & dosagem , Matriz Extracelular/química , Neoplasias/terapia , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiação , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/química , Fibrinogênio/efeitos da radiação , Géis , Humanos , Injeções Intravenosas , Metabolômica , Camundongos , Neoplasias/metabolismo , Trombina/administração & dosagem , Trombina/química , Trombina/efeitos da radiação , Terapia por Ultrassom/métodos , Ondas Ultrassônicas
2.
Pharm Res ; 37(10): 193, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32914377

RESUMO

PURPOSE: The incidence of breast cancer worldwide has been on the rise since the late 1970s, and it has become a common tumor that threatens women's health. Aminoglutethimide (AG) is a common treatment of breast cancer. However, current treatments require frequent dosing that results in unstable plasma concentration and low bioavailability, risking serious adverse reactions. Our goal was to develop a molecularly imprinted polymer (MIP) based delivery system to control the release of AG and demonstrate the availability of this drug delivery system (DDS), which was doped with carbon nanotube with aid of metal-organic gel. METHODS: Preparation of MIP was optimized by key factors including composition of formula, ratio of monomers and drug loading concentration. RESULTS: By using multi-walled carbon nanotubes (MWCNT) and metal-organic gels (MOGs), MIP doubled the specific surface area, pore volume tripled and the IF was 1.6 times than the reference. Compared with commercial tablets, the relative bioavailability was 143.3% and a more stable release appeared. CONCLUSIONS: The results highlight the influence of MWCNT and MOGs on MIP, which has great potential as a DDS.


Assuntos
Aminoglutetimida/química , Antineoplásicos Hormonais/química , Complexos de Coordenação/química , Sistemas de Liberação de Medicamentos/métodos , Nanotubos de Carbono/química , Aminoglutetimida/administração & dosagem , Aminoglutetimida/farmacocinética , Animais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacocinética , Complexos de Coordenação/administração & dosagem , Compostos Férricos/química , Géis/administração & dosagem , Géis/química , Humanos , Células MCF-7 , Masculino , Impressão Molecular/métodos , Ratos , Ácidos Tricarboxílicos/química
3.
Quintessence Int ; 51(10): 788-797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32901243

RESUMO

OBJECTIVES: This split-mouth study assessed the bleaching sensitivity (risk and intensity) and color change after in-office bleaching using a desensitizing-containing (5% potassium nitrate) and a desensitizing-free 35% hydrogen peroxide gel. The null hypothesis was that there would be no differences between study groups regarding bleaching sensitivity. METHOD AND MATERIALS: Sixty patients participated in this split-mouth study. The subjects received desensitizing-containing hydrogen peroxide in half of the maxillary arch, and the other half received a desensitizing-free hydrogen peroxide, defined by random sequence, in two dental bleaching sessions. The bleaching sensitivity was evaluated during bleaching and from 1 h to 48 h after each bleaching session using a visual analog scale and numeric rating scale; the McNemar test, the Wilcoxon signed-rank test, and the Student-Newman-Keuls test were used for statistical analysis. The color was measured at baseline and 30 days post-bleaching, evaluated with paired t tests (P = .05). RESULTS: Statistically similar risks of bleaching sensitivity were observed (P = 1.000), but the intensity of bleaching sensitivity was lower (P < .011) on average by 1.32 visual analog scale units in the group bleached with the desensitizer-containing gel during up to 24 h assessment times. No statistical difference in color change was observed between groups (P > .321). CONCLUSION: The incorporation of 5% potassium nitrate into in-office bleaching gels does not reduce the risk of bleaching sensitivity, but it reduces its intensity slightly without jeopardizing color change.


Assuntos
Sensibilidade da Dentina , Clareadores Dentários , Clareamento Dental , Sensibilidade da Dentina/induzido quimicamente , Método Duplo-Cego , Géis , Humanos , Peróxido de Hidrogênio , Clareadores Dentários/efeitos adversos , Resultado do Tratamento
4.
Yonsei Med J ; 61(10): 868-874, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32975061

RESUMO

PURPOSE: To investigate the efficacy and safety of a newly developed thermo-responsive sol-gel, ABT13107, for reducing the formation of intrauterine adhesions (IUAs) after hysteroscopic surgery. MATERIALS AND METHODS: In this multicenter, prospective, randomized trial (Canadian Task Force classification I), 192 women scheduled to undergo a hysteroscopic surgery at one of the eight university hospitals in South Korea were randomized into the ABT13107 group or the comparator (Hyalobarrier®) group in a 1:1 ratio. During hysteroscopic surgery, ABT13107 or Hyalobarrier® was injected to sufficiently cover the entire intrauterine cavity. RESULTS: The patients returned to their respective sites for safety assessments at postoperative weeks 1 and 4 and for efficacy assessments at postoperative week 4. The post-surgery incidence of IUAs was 23.4% in the ABT13107 group and 25.8% in the comparator group; this difference met the criteria for ABT13107 to be considered as not inferior to the comparator. No differences were found in the extent of adhesions, types of adhesions, or the cumulative American Fertility Society score between the two treatment groups. Most adverse events were mild in severity, and no serious adverse events occurred. CONCLUSION: ABT13107, a new anti-adhesive barrier containing hyaluronic acid, was not inferior to the highly viscous hyaluronic acid anti-adhesive barrier, Hyalurobarrier® in IUA formation after hysteroscopic surgery (Clinical trial registration No. NCT04007211).


Assuntos
Géis/administração & dosagem , Ácido Hialurônico/administração & dosagem , Histeroscopia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Aderências Teciduais/prevenção & controle , Doenças Uterinas/cirurgia , Adulto , Feminino , Géis/uso terapêutico , Humanos , Ácido Hialurônico/uso terapêutico , Incidência , Gravidez , Estudos Prospectivos , República da Coreia , Índice de Gravidade de Doença , Aderências Teciduais/etiologia , Resultado do Tratamento , Doenças Uterinas/etiologia
5.
Medicine (Baltimore) ; 99(31): e21165, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756094

RESUMO

GOALS: The aim of this study was to evaluate the effectiveness of adding a gelling agent to pureed diets to prevent aspiration pneumonia in elderly patients with moderate to severe dysphagia. BACKGROUND: Pureed diets are often used to reduce aspiration in patients with dysphagia. However, the ideal texture of a pureed diet to prevent aspiration pneumonia remains unclear. MATERIALS AND METHODS: We prospectively conducted a randomized, crossover trial of pureed rice with or without a gelling agent in patients with moderate to severe dysphagia (ClincialTrials.gov number, NCT03163355). The primary outcome measure was pharyngeal residuals using an endoscopic scoring system. The secondary outcome was the sense of material remaining in the throat following swallowing. RESULTS: Sixty two patients (58% men), mean age 83 ±â€Š9 years with moderate to severe dysphagia were included. Residuals in the throat were significantly less likely with pureed rice with than without the gelling agent (median cyclic ingestion score (range); 1 (0-4) vs 2 (0-4); P = .001). Irrespective of the presence or absence of the gelling agent, the sense of material remaining in the throat was significantly less frequent in older patients (87 ±â€Š7.6 vs 75 ±â€Š9.1 years, P < .01; 86 ±â€Š7.3 vs 75 ±â€Š8.6 years, P < .01). CONCLUSIONS: Pureed diets containing a gelling agent may reduce the risk of aspiration pneumonia possibly by decreasing pharyngeal residues in elderly patients with moderate to severe dysphagia.


Assuntos
Transtornos de Deglutição/dietoterapia , Deglutição , Idoso Fragilizado , Géis/administração & dosagem , Oryza , Pneumonia Aspirativa/prevenção & controle , Idoso de 80 Anos ou mais , Estudos Cross-Over , Dieta , Feminino , Humanos , Masculino , Resultado do Tratamento
6.
Int J Nanomedicine ; 15: 4763-4778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753865

RESUMO

Introduction: Methotrexate exhibits poor cutaneous bioavailability and systemic side effects on topical administration, so there is an unmet need for a novel carrier and its optimized therapy. Methotrexate-loaded nanostructured lipid carriers (MTXNLCs) were formulated and characterized to determine in vitro drug release and evaluate the role of MTXNLC gel in the topical treatment of psoriasis. Methods: A solvent diffusion technique was employed to prepare MTXNLCs, which was optimized using 32 full factorial designs. The mean diameter and surface morphology of MTXNLCs was evaluated. The crystallinity of lyophilized MTXNLCs was characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). MTXNLCs were integrated in 1% w/w Carbopol 934 P gel base, and in vitro skin deposition studies in human cadaver skin (HCS) were carried out. Results: The optimized MTXNLCs were rod-shaped, with an average particle size of 253 ± 8.65 nm, a zeta potential of -26.4±0.86 mV, and EE of 54.00±1.49%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of MTX was found in HCS from MTXNLC gel (71.52 ±1.13%) as compared to MTX plain gel (38.48±0.96%). In vivo studies demonstrated significant improvement in therapeutic response and reduction in local side effects with MTXNLCs-loaded gel in the topical treatment of psoriasis. Anti-psoriatic efficacy of MTXNLCs 100 ug/cm2 compared with plain MTX gel was evaluated using imiquimod (IMQ)-induced psoriasis in BALB/c mice. The topical application of MTXNLCs to the mouse ear resulted in a significant reduction of psoriatic area and severity index, oxidative stress, inflammatory cytokines like TNF-α, IL-1ß, and IL-6 and IMQ-induced histopathological alterations in mouse ear samples. Conclusion: Developed formulation of MTXNLC gel demonstrated better anti-psoriatic activity and also displayed prolonged and sustained release effect, which shows that it can be a promising alternative to existing MTX formulation for the treatment of psoriasis.


Assuntos
Composição de Medicamentos , Géis/química , Imiquimode/uso terapêutico , Inflamação/tratamento farmacológico , Lipídeos/química , Metotrexato/uso terapêutico , Nanoestruturas/química , Psoríase/tratamento farmacológico , Administração Cutânea , Administração Tópica , Animais , Catalase/metabolismo , Citocinas/metabolismo , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Glutationa/metabolismo , Humanos , Inflamação/patologia , Malondialdeído/metabolismo , Camundongos Endogâmicos BALB C , Nanoestruturas/ultraestrutura , Tamanho do Órgão , Superóxido Dismutase/metabolismo
7.
Int J Nanomedicine ; 15: 5113-5129, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764940

RESUMO

Background: Low bioavailability and poor permeability of the blood-brain barrier are problematic when delivering therapeutic agents and particularly anti-human immunodeficiency virus therapy to the central nervous system. The intranasal route offers an alternative for central nervous system delivery. Cubosomes have been reported as helpful vehicles for intranasal delivery of therapeutics to enable brain targeting. Objective: In this study, we aimed to develop the intranasal cubosomal thermogelling dispersion of saquinavir mesylate for central nervous system delivery. Methods: The Box-Behnken design was applied to study the effect of monoolein, Poloxamer 407, and polyvinyl alcohol as independent factors and the particle size, entrapment efficiency, gelation temperature, and stability index as responses. The optimized cubosomes were evaluated using transmission electron microscopy, ex vivo permeation, and in vivo pharmacokinetics. Results: The optimized formula consisting of monoolein (8.96%), Poloxamer 407 (17.45%), and polyvinyl alcohol (7.5%) was prepared and evaluated. Higher values for the steady-state flux, permeability coefficient, and enhancement factor were observed for the cubosomal thermogelling dispersion of saquinavir during ex vivo permeation in comparison with an aqueous suspension of saquinavir. From the pharmacokinetic profile, the relative bioavailability for the intranasal optimized formula was approximately 12-fold higher when compared with oral aqueous suspension and 2.5-fold greater when compared to the intranasal aqueous suspension of saquinavir. Conclusion: Overall, the saquinavir-loaded cubosomal thermogelling formulation is promising for central nervous system delivery by intranasal administration.


Assuntos
Portadores de Fármacos/química , Cristais Líquidos/química , Nanoestruturas/química , Saquinavir/farmacologia , Temperatura , Administração Intranasal , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Géis , Glicerídeos/química , Masculino , Tamanho da Partícula , Permeabilidade , Poloxâmero/química , Álcool de Polivinil/química , Saquinavir/administração & dosagem , Saquinavir/metabolismo
8.
PLoS One ; 15(8): e0237231, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853250

RESUMO

In this study, we examined the effect of differing gap lengths on regeneration of transected recurrent laryngeal nerves using silicon tubes containing type I collagen gel and the ability of this regeneration to result in restoration of vocal fold movements in rats. We simulated nerve gaps in Sprague-Dawley rats by transecting the left recurrent laryngeal nerves and bridged the nerve stumps using silicon tubes containing type 1 collagen gel. Three experimental groups, in which the gap lengths between the stumps were 1, 3, or 5 mm, were compared with a control group in which the nerve was transected but was not bridged. After surgery, we observed vocal fold movements over time with a laryngoscope. At week 15, we assessed the extent of nerve regeneration in the tube, histologically and electrophysiologically. We also assessed the degree of atrophy of the thyroarytenoid muscle (T/U ratio). Restoration of vocal fold movements was observed in 9 rats in the 1-mm group, in 6 rats in the 3-mm group, and in 3 rats in the 5-mm group. However, in most rats, restoration was temporary, with only one rat demonstrating continued vocal fold movements at week 15. In electromyograph, evoked potentials were observed in rats in the 1-mm and 3-mm groups. Regenerated tissue in the tube was thickest in the 1-mm group, followed by the 3-mm and 5-mm groups. The regenerated tissue showed the presence of myelinated and unmyelinated nerve fibers. In assessment of thyroarytenoid muscle atrophy, the T/U ratio was highest in the 1-mm group, followed by the 3-mm and 5-mm groups. We successfully regenerated the nerves and produced a rat model of recurrent laryngeal nerve regeneration that demonstrated temporary recovery of vocal fold movements. This rat model could be useful for assessing novel treatments developing in the future.


Assuntos
Colágeno/uso terapêutico , Regeneração Nervosa , Traumatismos do Nervo Laríngeo Recorrente/terapia , Nervo Laríngeo Recorrente/fisiopatologia , Animais , Materiais Biocompatíveis/química , Colágeno/administração & dosagem , Modelos Animais de Doenças , Géis/administração & dosagem , Géis/uso terapêutico , Masculino , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Nervo Laríngeo Recorrente/fisiologia , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Silício/química
9.
PLoS One ; 15(8): e0236164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760085

RESUMO

Hyaluronan (HA) is a nonsulfated glycosaminoglycan that has been widely used for biomedical applications. Here, we have analyzed the effect of HA on the rescue of primary cells under stress as well as its potential to recover muscle atrophy and validated the developed model in vitro using primary muscle cells derived from rats. The potentials of different HAs were elucidated through comparative analyses using pharmaceutical grade a) high (HHA) and b) low molecular weight (LHA) hyaluronans, c) hybrid cooperative complexes (HCC) of HA in three experimental set-ups. The cells were characterized based on the expression of myogenin, a muscle-specific biomarker, and the proliferation was analyzed using Time-Lapse Video Microscopy (TLVM). Cell viability in response to H2O2 challenge was evaluated by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression of the superoxide dismutase enzyme (SOD-2) was assessed by western blotting. Additionally, in order to establish an in vitro model of atrophy, muscle cells were treated with tumor necrosis factor-alpha (TNF-α), along with hyaluronans. The expression of Atrogin, MuRF-1, nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB), and Forkhead-box-(Fox)-O-3 (FoxO3a) was evaluated by western blotting to elucidate the molecular mechanism of atrophy. The results showed that HCC and HHA increased cell proliferation by 1.15 and 2.3 folds in comparison to un-treated cells (control), respectively. Moreover, both pre- and post-treatments of HAs restored the cell viability, and the SOD-2 expression was found to be reduced by 1.5 fold in HA-treated cells as compared to the stressed condition. Specifically in atrophic stressed cells, HCC revealed a noteworthy beneficial effect on the myogenic biomarkers indicating that it could be used as a promising platform for tissue regeneration with specific attention to muscle cell protection against stressful agents.


Assuntos
Ácido Hialurônico/farmacologia , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/terapia , Medicina Regenerativa/métodos , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/metabolismo , Géis , Humanos , Ácido Hialurônico/química , Peróxido de Hidrogênio/toxicidade , Microscopia Intravital , Peso Molecular , Fibras Musculares Esqueléticas/patologia , Atrofia Muscular/patologia , Miogenina/análise , Miogenina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Cultura Primária de Células , Ratos , Superóxido Dismutase/análise , Superóxido Dismutase/metabolismo , Imagem com Lapso de Tempo , Fator de Necrose Tumoral alfa/metabolismo
10.
Int J Nanomedicine ; 15: 5253-5264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801690

RESUMO

Background and Aim: Flibanserin (FLB) is a multifunctional serotonergic agent used for treating hypoactive sexual desire disorder in premenopausal women via oral administration. FLB has a reported limited oral bioavailability of 33% that could be attributed to the drug's first-pass metabolism. In addition, FLB has a pH-dependent solubility that could be a challenging factor for drug dissolution in the body neutral fluid, and consequently, absorption via mucosal barriers. Thus, this work aims at investigating the potential of utilizing nanostructured lipid carriers (NLCs) to overcome the aforementioned drawbacks and to enhance nose-to-brain drug delivery. Methods: Box-Behnken design was applied to explore the impact of solid lipid % (SL%, X 1), liquid lipid % (LL%, X 2), and sonication time (ST, X 3) on particle size. The optimized NLC formulation was characterized and incorporated into gellan gum in situ gel. The prepared gel was subjected to in vitro drug release, in vivo pharmacokinetic performance, and histopathological assessment in rats. Results: Statistical analysis revealed a significant negative effect for both SL% and ST on NLCs size. In contrast, a significant positive effect was observed for the LL%. The optimized formulation showed spherical shape with vesicular size of 114.63 nm. The optimized FLB-NLC in situ gel exhibited adequate stability and enhanced in vitro release compared to raw FLB control gel. The plasma and brain concentrations of the drug after nasal administration in rats increased by more than 3-6-fold, respectively, compared to raw FLB in situ gel. In addition, the histopathological studies revealed the absence of any pathological signs. Conclusion: The aforementioned results highlight the safety of FLB-NLC in situ nasal gel and its potential to improve the drug bioavailability and brain delivery.


Assuntos
Benzimidazóis/administração & dosagem , Encéfalo/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Nanoestruturas/administração & dosagem , Administração Intranasal , Animais , Benzimidazóis/farmacocinética , Disponibilidade Biológica , Portadores de Fármacos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Géis , Lipídeos/administração & dosagem , Lipídeos/química , Masculino , Nanoestruturas/química , Tamanho da Partícula , Polissacarídeos Bacterianos/química , Ratos Wistar , Solubilidade
11.
J Comput Assist Tomogr ; 44(5): 759-765, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32842061

RESUMO

OBJECTIVE: To compare the intravoxel incoherent motion (IVIM) parameters of rectal tumors before and after lumen distension obtained with sonography transmission gel. METHODS: Twenty-five patients were enrolled. The multiple b values of IVIM including 0, 20, 50, 100, 150, 200, 400, 600, 800, 1000, 1500, and 2000 s/mm. Two blinded readers have drawn the region of interests and calculated the D, D*, and f values. Interobserver variability between the 2 readers was measured by intraclass correlation coefficients and Altman-Bland plots. The intergroup differences of the average values were compared with the paired sample t test. RESULTS: After distention, the interrater agreement of the D* value increased obviously (from 0.547 to 0.692) and that of the D and f values increased slightly (from 0.731 and 0.618 to 0.807 and 0.666). The difference in the D value had statistical significance (P = 0.0043). CONCLUSIONS: Intraluminal distension can increase the repeatability of IVIM parameters and the value of IVIM.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Géis/uso terapêutico , Neoplasias Retais/diagnóstico por imagem , Reto/diagnóstico por imagem , Adulto , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Variações Dependentes do Observador , Neoplasias Retais/fisiopatologia , Reto/fisiopatologia , Ultrassonografia
12.
Int J Nanomedicine ; 15: 4079-4090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606665

RESUMO

Purpose: The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis. Methods: Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis. Results: The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel. Conclusion: The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Imidazóis/uso terapêutico , Muco/química , Tiofenos/uso terapêutico , Adesividade , Animais , Anti-Infecciosos/farmacologia , Biomarcadores/metabolismo , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Géis , Humanos , Imidazóis/farmacologia , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Mediadores da Inflamação/metabolismo , Lipossomos/ultraestrutura , Mucinas/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Ovinos , Eletricidade Estática , Tiofenos/farmacologia , Vagina/patologia , beta-Glucanas/metabolismo
13.
Food Chem ; 332: 127294, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615378

RESUMO

The pH-shift process for isolation of gel-forming proteins from fish processing by-products was extended to allow parallel isolation of fish oil. Subjecting the floating emulsion layer formed during pH-shift processing of salmon by-products to pH-adjustment or freeze/thawing efficiently released the emulsified oil at 4 °C. However, for herring by-products higher temperature (10 °C) and a combination of the emulsion-breaking techniques was required for efficient oil release. Oil recovery yield using the adjusted pH-shift process was lower than with classic heat-induced oil isolation (90 °C/20 min), but pH-shift-produced oils had higher amounts of n-3 polyunsaturated fatty acids (n-3 PUFA). Also, alkaline pH-shift processing produced oils with remarkably less oxidation products and free fatty acids compared with acid pH-shift process or heat-induced isolation. Extending the pH-shift process with emulsion breaking techniques can thus be a promising biorefinery approach for parallel cold production of high-quality fish oil and gel-forming proteins from fish by-products.


Assuntos
Temperatura Baixa , Óleos de Peixe/isolamento & purificação , Proteínas de Peixes/química , Qualidade dos Alimentos , Animais , Reatores Biológicos , Géis , Temperatura Alta , Oxirredução
14.
Food Chem ; 332: 127373, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619941

RESUMO

In the present study, effects of riboflavin (RF) and kelp polyphenol extracts (KPE) on mackerel (Scomberomorus Niphonius) myofibrillar protein (MP) gel were studied with or without ultraviolet A (UVA) irradiation treatment. The gel strength was increased with the addition of RF and KPE under UVA irradiation. Analysis of the proteins in the gel indicated that the carbonyl content increased, while the contents of total sulfhydryl and amino groups decreased. The proteins appeared to have no α-helix structures, and the endogenous tryptophan content appeared to decrease. The results of SDS-PAGE indicated that the RF and KPE treated samples under UVA irradiation showed massive MP cross-linking by covalent bonds. Electron spin resonance (ESR) results indicated that UVA irradiation generated free radicals in RF and KPE, which ultimately led to an improvement in MP gel properties. It also indicated that KPE could prevent the occurrence of peroxidation to improve the gel properties.


Assuntos
Proteínas de Peixes/química , Kelp/química , Perciformes , Polifenóis/química , Riboflavina/química , Raios Ultravioleta , Animais , Radicais Livres/química , Géis
15.
Cochrane Database Syst Rev ; 7: CD001298, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32683695

RESUMO

BACKGROUND: Adhesions are fibrin bands that are a common consequence of gynaecological surgery. They are caused by conditions that include pelvic inflammatory disease and endometriosis. Adhesions are associated with comorbidities, including pelvic pain, subfertility, and small bowel obstruction. Adhesions also increase the likelihood of further surgery, causing distress and unnecessary expenses. Strategies to prevent adhesion formation include the use of fluid (also called hydroflotation) and gel agents, which aim to prevent healing tissues from touching one another, or drugs, aimed to change an aspect of the healing process, to make adhesions less likely to form. OBJECTIVES: To evaluate the effectiveness and safety of fluid and pharmacological agents on rates of pain, live births, and adhesion prevention in women undergoing gynaecological surgery. SEARCH METHODS: We searched: the Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and Epistemonikos to 22 August 2019. We also checked the reference lists of relevant papers and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials investigating the use of fluid (including gel) and pharmacological agents to prevent adhesions after gynaecological surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. We assessed the overall quality of the evidence using GRADE methods. Outcomes of interest were pelvic pain; live birth rates; incidence of, mean, and changes in adhesion scores at second look-laparoscopy (SLL); clinical pregnancy, miscarriage, and ectopic pregnancy rates; quality of life at SLL; and adverse events. MAIN RESULTS: We included 32 trials (3492 women), and excluded 11. We were unable to include data from nine studies in the statistical analyses, but the findings of these studies were broadly in keeping with the findings of the meta-analyses. Hydroflotation agents versus no hydroflotation agents (10 RCTs) We are uncertain whether hydroflotation agents affected pelvic pain (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.52 to 2.09; one study, 226 women; very low-quality evidence). It is unclear whether hydroflotation agents affected live birth rates (OR 0.67, 95% CI 0.29 to 1.58; two studies, 208 women; low-quality evidence) compared with no treatment. Hydroflotation agents reduced the incidence of adhesions at SLL when compared with no treatment (OR 0.34, 95% CI 0.22 to 0.55, four studies, 566 women; high-quality evidence). The evidence suggests that in women with an 84% chance of having adhesions at SLL with no treatment, using hydroflotation agents would result in 54% to 75% having adhesions. Hydroflotation agents probably made little or no difference to mean adhesion score at SLL (standardised mean difference (SMD) -0.06, 95% CI -0.20 to 0.09; four studies, 722 women; moderate-quality evidence). It is unclear whether hydroflotation agents affected clinical pregnancy rate (OR 0.64, 95% CI 0.36 to 1.14; three studies, 310 women; moderate-quality evidence) compared with no treatment. This suggests that in women with a 26% chance of clinical pregnancy with no treatment, using hydroflotation agents would result in a clinical pregnancy rate of 11% to 28%. No studies reported any adverse events attributable to the intervention. Gel agents versus no treatment (12 RCTs) No studies in this comparison reported pelvic pain or live birth rate. Gel agents reduced the incidence of adhesions at SLL compared with no treatment (OR 0.26, 95% CI 0.12 to 0.57; five studies, 147 women; high-quality evidence). This suggests that in women with an 84% chance of having adhesions at SLL with no treatment, the use of gel agents would result in 39% to 75% having adhesions. It is unclear whether gel agents affected mean adhesion scores at SLL (SMD -0.50, 95% CI -1.09 to 0.09; four studies, 159 women; moderate-quality evidence), or clinical pregnancy rate (OR 0.20, 95% CI 0.02 to 2.02; one study, 30 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Gel agents versus hydroflotation agents when used as an instillant (3 RCTs) No studies in this comparison reported pelvic pain, live birth rate or clinical pregnancy rate. Gel agents probably reduce the incidence of adhesions at SLL when compared with hydroflotation agents (OR 0.50, 95% CI 0.31 to 0.83; three studies, 538 women; moderate-quality evidence). This suggests that in women with a 46% chance of having adhesions at SLL with a hydroflotation agent, the use of gel agents would result in 21% to 41% having adhesions. We are uncertain whether gel agents improved mean adhesion scores at SLL when compared with hydroflotation agents (MD -0.79, 95% CI -0.82 to -0.76; one study, 77 women; very low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. Steroids (any route) versus no steroids (4 RCTs) No studies in this comparison reported pelvic pain, incidence of adhesions at SLL or mean adhesion score at SLL. It is unclear whether steroids affected live birth rates compared with no steroids (OR 0.65, 95% CI 0.26 to 1.62; two studies, 223 women; low-quality evidence), or clinical pregnancy rates (OR 1.01, 95% CI 0.66 to 1.55; three studies, 410 women; low-quality evidence). No studies in this comparison reported on adverse events attributable to the intervention. AUTHORS' CONCLUSIONS: Gels and hydroflotation agents appear to be effective adhesion prevention agents for use during gynaecological surgery, but we found no evidence indicating that they improve fertility outcomes or pelvic pain, and further research is required in this area. It is also worth noting that for some comparisons, wide confidence intervals crossing the line of no effect meant that clinical harm as a result of interventions could not be excluded. Future studies should measure outcomes in a uniform manner, using the modified American Fertility Society score. Statistical findings should be reported in full. No studies reported any adverse events attributable to intervention.


Assuntos
Anticoagulantes/uso terapêutico , Glucocorticoides/uso terapêutico , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Substitutos do Plasma/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Soluções para Reidratação/uso terapêutico , Aderências Teciduais/prevenção & controle , Coeficiente de Natalidade , Soluções para Diálise/uso terapêutico , Feminino , Géis/uso terapêutico , Humanos , Icodextrina/uso terapêutico , Infertilidade Feminina/prevenção & controle , Dor Pélvica/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Gravidez , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Cirurgia de Second-Look , Aderências Teciduais/epidemiologia
16.
J Chromatogr A ; 1625: 461117, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709364

RESUMO

To obtain consistent chromatographic behavior, it is important to develop resin packing methods in accordance with the characteristics of each resin. Resins, particularly those with a significant level of compressibility, require proper knowledge of the packing methodology to ensure scalable performance. The study demonstrates the applicability of pressure-flow modeling based on the Blake-Kozeny equation for cellulose based resins, using the MEP HyperCel (Pall) resin as a case study. This approach enabled the understanding of the appropriate bed compressibility and the determination of the minimum column diameter that can predict bed integrity during commercial manufacturing scale operation. Studies suggested that scale-dependent wall effects become negligible for column diameters exceeding 20 cm. Pressure-flow modeling produced a minimum compression recommendation of 0.206 for the MEP HyperCel resin. Columns with diameters up to 80 cm packed with this bed compression yielded incompressible beds with pressure-flow curves consistent with model predictions. Model parameter (particle diameter, viscosity, porosity) values were then varied to demonstrate how changing operating conditions influence model predictions. This analysis supported the successful troubleshooting of unexpected high pressures at the commercial manufacturing scale using MEP HyperCel resin, further supporting the applicability of this approach.


Assuntos
Produtos Biológicos/isolamento & purificação , Cromatografia Líquida/métodos , Anticorpos Monoclonais/isolamento & purificação , Géis/química , Porosidade , Pressão , Viscosidade
17.
AAPS PharmSciTech ; 21(5): 185, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632542

RESUMO

The present study aimed to develop, characterize and evaluate the amphotericin B-loaded nanostructured lipid carriers (AmB-NLCs) for topical treatment of cutaneous leishmaniasis (CL) and vulvovaginal candidiasis (VVC). AmB-NLCs were characterized for particle size, zeta potential, encapsulation efficiency and surface morphology. Prepared NLCs were also characterized for in vitro drug release, ex vivo skin permeation and deposition before evaluating their in vitro and in vivo efficacy. Cytotoxicity of NLCs was assessed on MRC-5 cells, whereas skin irritation potential was evaluated in vivo using rats. Significant accumulation of drug in to the skin supported the topical application potential of drug-loaded NLCs. Encapsulation of AmB in NLCs resulted in enhanced in vitro potency against promastigotes and intracellular amastigotes of L. major JISH 118 (IC50 ± SEM = 0.02 ± 0.1 µM for both) compared with free drug (IC50 ± SEM = 0.15 ± 0.2 & 0.14 ± 0.0, respectively). Similar improved potency of AmB-NLCs was also observed for other Leishmania and fungal strains compared with drug solution. Topical application of AmB-NLCs on L. major-infected BALB/c mice caused a significant reduction in parasite burden per mg of lesion (65 × 108 ± 13) compared with the control group (> 167.8 × 108 ± 11). Topical AmB-NLCs gel demonstrated superior efficacy in the vaginal C. albicans rat model for VVC as compared with plain AmB gel. Moreover, results of in vitro cytotoxicity assay and in vivo skin irritation test confirmed AmB-NLCs to be non-toxic and safe for topical use. In conclusion, NLCs may have promising potential as carrier for topical treatment of various conditions of skin and mucosa.


Assuntos
Anfotericina B/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Nanoestruturas/administração & dosagem , Administração Tópica , Animais , Candidíase Vulvovaginal/metabolismo , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Géis/metabolismo , Humanos , Lipídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea
18.
Food Chem ; 333: 127538, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712546

RESUMO

The effects of water content; 15, 30, and 40% (w/w), water droplet size; d43 15.0-19.6 µm (larger) and d43 1.2-2.7 µm (smaller), and sodium alginate (0.5%, w/w) induced water gelation on crystallization kinetics and water and fat proton relaxation were studied in water-in-milk fat emulsions during in situ cooling from 40 °C to 5 °C. Anhydrous milk fat (AMF) and commercial butter were employed as two separate fat sources. Although emulsions were crystallized faster than the bulk fat, the variations in the water fraction and droplet size did not show major influence on crystallization properties. Smaller droplet size induced significant (p < 0.05) reduction in water mobility with a minimal effect of the temperature. In AMF-based emulsions, gelation of water phase not only immobilized the water molecules but also enhanced the rate of fat crystallization. Globular fat and serum solids in butter-based emulsions showed to fasten the water proton relaxation.


Assuntos
Ácidos Graxos/química , Leite/química , Movimento (Física) , Transição de Fase , Água/química , Animais , Manteiga/análise , Cristalização , Emulsões , Géis , Cinética , Temperatura
19.
Food Chem ; 332: 127401, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610261

RESUMO

Tofu gel was made by using citric acid (0.14%) in combination with varied volumetric ratios (e.g., 0-4%) of nano fish bone (NFB). The gel properties were investigated by colorimetry, penetration tests, scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR) spectroscopy. As the volumetric ratio increased from 0 to 3%, the soluble calcium concentrations of soymilk linearly increased from 1.78 to 6.42 mg/mL. Correspondently, yield, moisture and texture values of the tofu gel increased continuously (p < 0.05) while syneresis and whiteness decreased (p < 0.05). Furthermore, ionic bonds, hydrophobic interactions and hydrogen bonds increased by 140%, 40% and 10%, respectively. With the addition of NFB, the α-helices of the soybean proteins changed to ß-sheets and random coil structures. Additionally, the tofu gel network became more orderly and denser. The results confirmed that NFB can be utilized as a functional coagulant ingredient to improve the properties of acid-induced tofu gels.


Assuntos
Osso e Ossos/química , Ácido Cítrico/química , Peixes , Manipulação de Alimentos/métodos , Nanoestruturas/química , Alimentos de Soja/análise , Animais , Géis , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Infravermelho com Transformada de Fourier
20.
PLoS One ; 15(7): e0236171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702047

RESUMO

Cell-substrate adhesion of the social amoeba Dictyostelium discoideum, a model organism often used for the study of chemotaxis, is non-specific and does not involve focal adhesion complexes. Therefore, micropatterned substrates where adherent Dictyostelium cells are constrained to designated microscopic regions are difficult to make. Here we present a micropatterning technique for Dictyostelium cells that relies on coating the substrate with an ∼1µm thick layer of polyethylene glycol (PEG) gel. We show that, when plated on a substrate with narrow parallel stripes of PEG-gel and glass, Dictyostelium cells nearly exclusive adhere to and migrate along the glass stripes, thus providing a model system to study one-dimensional migration of amoeboid cells. Surprisingly, we find substantial differences in the adhesion to PEG-gel and glass stripes between vegetative and developed cells and between two different axenic laboratory strains of Dictyostelium, AX2 and AX4. Even more surprisingly, we find that the distribution of Dictyostelium cells between PEG-gel and glass stripes is significantly affected by the expression of several fluorescent protein markers of the cytoskeleton. We carry out atomic force microscopy based single cell force spectroscopy measurements that confirm that the force of adhesion to PEG-gel substrate can be significantly different between vegetative and developed cells, AX2 and AX4 cells, and cells with and without fluorescent markers. Thus, the choice of parental background, the degree of development, and the expression of fluorescent protein markers can all have a profound effect on cell-substrate adhesion and should be considered when comparing migration of cells and when designing micropatterned substrates.


Assuntos
Movimento Celular , Dictyostelium/citologia , Corantes Fluorescentes/metabolismo , Microtecnologia/métodos , Polietilenoglicóis/farmacologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Dictyostelium/efeitos dos fármacos , Géis/farmacologia , Análise Espectral
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