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1.
Allergol Immunopathol (Madr) ; 49(2): 191-207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33641309

RESUMO

Eosinophils are the major inflammatory cells which play a crucial role in the development of allergic and non-allergic asthma phenotypes. Eosinophilic asthma is the most heterogeneous phenotype where activated eosinophils are reported to be significantly associated with asthma severity. Activated eosinophils display an array of cell adhesion molecules that not only act as an activation marker, suitable for assessing severity, but also secrete several tissue factors, cytokines and chemokines which modulate the clinical severity. Eosinophil activations are also strictly associated with activation of other hetero cellular populations like neutrophils, macrophages, mast cells, and platelets which culminate in the onset and progression of abnormal phenotypes such as bronchoconstriction, allergic response, fibrosis instigated by tissue inflammation, epithelial injury, and oxidative stress. During the activated state, eosinophils release several potent toxic signaling molecules such as major basic proteins, eosinophil peroxidase, eosinophil cationic protein (ECP), and lipid mediators, rendering tissue damage and subsequently leading to allergic manifestation. The tissue mediators render a more complex manifestation of a severe phenotype by activating prominent signaling cross-talk. Here, in the current review with the help of search engines of PubMed, Medline, etc, we have tried to shed light and explore some of the potent determinants regulating eosinophil activation leading to asthma phenotype.


Assuntos
Asma/imunologia , Comunicação Celular/imunologia , Eosinófilos/imunologia , Remodelação das Vias Aéreas/imunologia , Animais , Asma/sangue , Asma/diagnóstico , Asma/patologia , Plaquetas/imunologia , Brônquios/imunologia , Brônquios/patologia , Broncoconstrição/imunologia , Modelos Animais de Doenças , Eosinófilos/metabolismo , Fibrose , Humanos , Contagem de Leucócitos , Macrófagos/imunologia , Mastócitos/imunologia , Camundongos , Neutrófilos/imunologia , Estresse Oxidativo/imunologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Índice de Gravidade de Doença
2.
Chemistry ; 20(20): 6047-53, 2014 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-24692292

RESUMO

Phenanthroline-based chiral ligands L(1) and L(2) as well as the corresponding Eu(III) and Tb(III) complexes were synthesized and characterized. The coordination compounds show red and green emission, which was explored for the sensing of a series of anions such as F(-), Cl(-), Br(-), I(-), NO3(-), NO2(-), HPO4(2-), HSO4(-), CH3COO(-), and HCO3(-). Among the anions, HPO4(2-) exhibited a strong response in the emission property of both europium(III) and terbium(III) complexes. The complexes showed interactions with the nucleoside phosphates adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP). Owing to this recognition, these complexes have been applied as staining agents in the microalgal cell Chlorella vulgaris. The stained microalgal cells were monitored through fluorescence microscopy and scanning electron microscopy. Initially, the complexes bind to the outer cell wall and then enter the cell wall through holes in which they probably bind to phospholipids. This leads to a quenching of the luminescence properties.


Assuntos
Chlorella vulgaris/química , Complexos de Coordenação/química , Európio/química , Substâncias Luminescentes/química , Fosfatos/análise , Térbio/química , Difosfato de Adenosina/análise , Monofosfato de Adenosina/análise , Trifosfato de Adenosina/análise , Chlorella vulgaris/citologia , Complexos de Coordenação/síntese química , Ligantes , Microscopia de Fluorescência
3.
Nat Prod Res ; 38(4): 624-628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36799628

RESUMO

Grewia bracteata Roth stem was investigated for its anticancer potential for the first time. Initially, polarity-guided extracts from three solvents were screened on HeLa, HCT- 116 and MCF-7 tumours cells. The results revealed that ethyl acetate extract (GSE) significantly (p < 0.05) inhibited HeLa, HCT- 116 and MCF-7 cells with respective IC50 values of 30.58, 14.26 and 22.91 µg/mL. GSE inhibited HCT-116 cells with 6- and 21-folds higher than hexane (GSN) and methanol (GSM) extracts, respectively. Hence, column chromatography of GSE was performed and fractionated to 18 fractions. The obtained fractions were further tested on HCT-116 cells. Amongst, the fractions HF6 and DF1 were active with the respective IC50 values of 25.35 and 31.28, µg/mL (p < 0.05). These active fractions were profiled using H1-NMR, C13-NMR and LC-MS/MS analysis, and found the presence of pentacyclic triterpenoids like betulin diacetate and ursolic acid.


Assuntos
Grewia , Extratos Vegetais , Humanos , Triterpenos Pentacíclicos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Grewia/química , Cromatografia Líquida , Espectrometria de Massas em Tandem
4.
J Biomol Struct Dyn ; : 1-14, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38284378

RESUMO

The textile industry utilizing affordable azo dyes is a high threat to aquatic life and causes environmental problems due to their toxicity. Biodegradation of azo dyes employing microbes and enzymes has proved to be an efficient method for treating industrial effluent. This study used the novel microbial consortium to decolorize reactive azo dyes (Reactive Red 120; Reactive Black 5 and Reactive Blue 13), and its azo-reductase activity was evaluated. The metagenomic analysis of the consortium identified azo-reductase-producing bacterial species. The molecular docking revealed that PpAzoR from Pseudomonas putida had the highest binding affinities for all the three dyes such as Reactive Black 5 (-9.3 kcal/mol), Reactive Blue 13 (-9.8 kcal/mol) and Reactive Red 120 (-10.7 kcal/mol). The structural rigidity and stability of the docked complex were confirmed through MD simulations evaluated across multiple descriptors from the simulation trajectories. Further, MMPBSA analysis validated the results that binding of the ligands, i.e. dye molecules Reactive Black (RB5), Reactive Blue (RB13) and Reactive Red (RR120) binding with the Azoreductase (PpAzoR) to the screened Azo-dyes was spontaneous. Based on molecular dynamics simulations for 100 ns, RR 120 showed the highest binding affinity (-411.336 ± 46.799 KJ/mol), followed by RB5 (-288.012 ± 33.371 KJ/mol). The dyes (RR120 and RB5) exhibited stable interactions with the target azoreductase (PpAzoR). The present study provides insights that PpAzoR shows the highest decolorization potency, which could be interpreted as a potential dye-degrading protein based on dye-degrading assay findings.Communicated by Ramaswamy H. Sarma.


>90% decolourization observed for all reactive dyes at 72 hAzo reductase-producing bacterial species were identified using metagenomicsPseudomonas putida (PpAzoR) showed maximum binding affinity with all three dyesPositive correlation was established between dye decolourization and in-silico results.

5.
Adv Drug Deliv Rev ; 203: 115119, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37898338

RESUMO

Inflammation is prevalent and inevitable in daily life but can generally be accommodated by the immune systems. However, incapable self-healing and persistent inflammation can progress to chronic inflammation, leading to prevalent or fatal chronic diseases. This review comprehensively covers the topic of emerging drug delivery systems (DDSs) for the treatment of chronic inflammatory diseases (CIDs). First, we introduce the basic biology of the chronic inflammatory process and provide an overview of the main CIDs of the major organs. Next, up-to-date information on various DDSs and the associated strategies for ensuring targeted delivery and stimuli-responsiveness applied to CIDs are discussed extensively. The implementation of traditional routes of drug administration to maximize their therapeutic effects against CIDs is then summarized. Finally, perspectives on future DDSs against CIDs are presented.


Assuntos
Sistemas de Liberação de Medicamentos , Inflamação , Humanos , Inflamação/tratamento farmacológico , Doença Crônica
6.
Artigo em Inglês | MEDLINE | ID: mdl-36807851

RESUMO

In recent years, circular economy has become a matter of great importance because of its ability to contribute toward economic, environmental, and social aspects of the sustainability. The circular economy approaches help in resource conservation by reducing, reusing, and recycling products/parts/components/materials. On the other hand, Industry 4.0 is coupled with emerging technologies, which support the firms in efficient resource utilization. These innovative technologies can transform the present manufacturing organizations by reducing resource extraction, CO2 emissions, environmental damage, and power consumption and improve it into a more sustainable manufacturing organization. Industry 4.0 along with circular economy concepts greatly improves the circularity performance. However, there is no framework found for measuring the circularity performance of the firm. Therefore, the current study aims to develop a framework for measuring performance in terms of circularity percentage. In this work, graph theory and matrix approach are employed for measuring the performance based on a sustainable balanced scorecard such as internal process, learning and growth, customer and financial with environmental and social perspectives. A case of an Indian barrel manufacturing organization is discussed for the illustration of proposed methodology. Based on "circularity index" of the organization and the maximum possible circularity index, the circularity was found to be 5.10%. It indicates that there is a huge potential for the improvement in the circularity of the organization. An in-depth sensitivity analysis and comparison are also performed to validate the findings. There are very few studies on measuring the circularity. The study developed the approach for measuring circularity, which may be utilized by industrialists and practitioners for improving the circularity.

7.
J Biomol Struct Dyn ; : 1-10, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37350097

RESUMO

Diabetes is a common lifestyle disorder found in populations of different age groups. Maltase-glucoamylase catalyses the release of the glucose molecule in the final enzymatic reaction of starch digestion; therefore, inhibition of maltase-glucoamylase is one of the approaches in the development of therapeutics for diabetes. Citrullus colocynthis is commonly recommended in Ayurveda for the treatment of diabetes. The current study applied a structure-based drug design approach to repurpose the phytochemicals of Citrullus colocynthis to identify potential inhibitors for maltase-glucoamylase. 70 phytochemicals of Citrullus colocynthis were screened against maltase-glucoamylase and top 5 molecules 8-p-hydroxybenzylisovitexin, isoorientin, cucurbitacin B, cucurbitacin E, and cucurbitacin I with significant binding energy of -10 kcal/mol, -9.9 kcal/mol, -9.6 kcal/mol, -9.2 kcal/mol, and -7.7 kcal/mol were identified. Furthermore, MMGBSA, pharmacokinetics properties and toxicity prediction were performed on the five identified molecules and top 3 molecules were selected for molecular dynamics (MD) simulation. It was observed from the structural flexibility and dynamic behaviour of the systems that conformational changes were noticed in the complexes as compared to its native state, which suggests that the 3 molecules, namely 8-p-hydroxybenzylisovitexin, isoorientin, and cucurbitacin I of Citrullus colocynthis may act as inhibitors for maltase-glucoamylase.Communicated by Ramaswamy H. Sarma.

8.
Carbohydr Polym ; 316: 121088, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37321716

RESUMO

Nanozymes have prominent catalytic activities with high stability as a substitute for unstable and expensive natural enzymes. However, most nanozymes are metal/inorganic nanomaterials, facing difficulty in clinical translation due to their unproven biosafety and limited biodegradability issues. Hemin, an organometallic porphyrin, was newly found to possess superoxide dismutase (SOD) mimetic activity along with previously known catalase (CAT) mimetic activity. However, hemin has poor bioavailability due to its low water solubility. Therefore, a highly biocompatible and biodegradable organic-based nanozyme system with SOD/CAT mimetic cascade reaction activity was developed by conjugating hemin to heparin (HepH) or chitosan (CS-H). Between them, Hep-H formed a smaller (<50 nm) and more stable self-assembled nanostructure and even possessed much higher and more stable SOD and CAT activities as well as the cascade reaction activity compared to CS-H and free hemin. Hep-H also showed a better cell protection effect against reactive oxygen species (ROS) compared to CS-H and hemin in vitro. Furthermore, Hep-H was selectively delivered to the injured kidney upon intravenous administration at the analysis time point (24 h) and exhibited excellent therapeutic effects on an acute kidney injury model by efficiently removing ROS, reducing inflammation, and minimizing structural and functional damage to the kidney.


Assuntos
Injúria Renal Aguda , Hemina , Humanos , Catalase , Hemina/química , Espécies Reativas de Oxigênio , Heparina , Antioxidantes , Superóxido Dismutase , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico
9.
J Control Release ; 344: 160-172, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35247490

RESUMO

Nanoreactors for scavenging reactive oxygen species (ROS), a major factor in inflammatory diseases, can reduce overproduced ROS, and thus can prevent further progress of the diseases or facilitate the regeneration of damaged inflamed tissues. Herein, we designed a pluronic-based nanocarrier loaded with dual antioxidant enzymes present in vivo (superoxide dismutase (SOD) and catalase (CAT)) as a nanoreactor system for the regeneration of inflammatory tissue. The catalytic activity of each enzyme was enhanced by loading it into the nanocarrier. More importantly, the nanocarrier could enhance the cascade reaction between SOD and CAT, which converts the superoxide anion to oxygen. The synergistic anti-inflammatory effect of the nanoreactor based on the cascade reaction was verified in vitro. Furthermore, in an inflammatory bowel disease (IBD) mouse model, the dual enzyme (SOD/CAT)-loaded nanocarrier could result in significantly enhanced tissue regeneration and notably alleviated inflammation activities upon intravenous administration of them compared to other control groups, including single enzyme (SOD or CAT)-loaded nanocarrier and the free mixture of both enzymes without the nanocarrier. Thus, the efficacy of the nanoreactor for the cascade reaction on tissue regeneration in vivo was proved. Accordingly, the nanoreactor could be applied for tissue regeneration therapy against various inflammatory diseases.


Assuntos
Antioxidantes , Nanotecnologia , Regeneração , Superóxido Dismutase , Animais , Catalase , Camundongos , Espécies Reativas de Oxigênio
10.
Mater Sci Eng C Mater Biol Appl ; 119: 111596, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33321640

RESUMO

Excessive reactive oxygen species (ROS) and unresolved inflammations are the major causes of impaired wound healing as they overwhelm the cellular antioxidant system and impede the healing process. In this study, we examined the application of Prussian blue (PB) nanozyme as a novel material for cutaneous wound healing through the alleviation of excessive ROS and inflammation modulation. The PB nanoparticles not only exhibited hydrogen peroxide (H2O2) degradation activity but also showed strong superoxide scavenging ability. PB nanozyme mitigated the intracellular ROS at a high oxidative stress environment, resulting in a pronounced cytoprotective effect. Moreover, PB nanozyme also displayed significant anti-inflammatory activity, as evident from the suppression of inflammatory mediators in the lipopolysaccharide (LPS) induced macrophage cells. Encouraged by the in vitro results, we evaluated the in vivo therapeutic efficacy of PB nanozyme in a full-thickness cutaneous wound model combined with LPS treatment to mimic bacterial infection. The beneficial effects of topically applied PB nanozyme on wound healing and tissue regeneration were evident compared to the control. The periodical administration of a low amount (50 µg × 4) of PB nanoparticles exhibited faster wound closure as well as collagen deposition, maturation, and organization. Moreover, the PB treatment effectively induced the differentiation of keratinocytes, enhanced the neovascularization, and reduced macrophage burden in the entire wound site. Thus, PB nanozyme not only accelerated the healing process in an infection-mimicking cutaneous wound model but also exhibited tissue regeneration characteristics owing to the synergistic effect of ROS-scavenging and anti-inflammatory activities.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ferrocianetos , Pele , Cicatrização
11.
ACS Appl Mater Interfaces ; 13(22): 25649-25662, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-33974389

RESUMO

Mesenchymal stem cell (MSC) based therapy holds great potential for treating numerous diseases owing to their capability to heal injured tissue/organs through paracrine factors secretion and immunomodulation. Despite the high hopes, the low viability of transplanted cells in the injured tissues due to the elevated oxidative stress levels remains the largest obstacle in MSC-based cell therapy. To achieve desired therapeutic efficiency, the survival of the transplanted MSCs in the high oxidative stress environment needs to be ensured. Herein, we proposed the use of a ROS-scavenging nanozyme to protect transplanted MSCs from oxidative stress-mediated apoptosis and thereby improve the therapeutic effect. Prussian blue (PB) nanoparticles as a biocompatible ROS-scavenging nanozyme were incorporated into the MSCs without affecting the stemness and differentiation potential of MSCs. The nanozyme impregnation significantly improved the survival of MSCs in a high oxidative stress condition as well as augmented their paracrine effect and anti-inflammatory properties, resulting in a profound therapeutic effect in vivo in the liver ischemia-reperfusion (I/R) injury animal model. Our results indicated that the nanozyme incorporation into MSCs is a simple but efficient way to improve the therapeutic potential of MSC-based cell therapy.


Assuntos
Modelos Animais de Doenças , Ferrocianetos/química , Inflamação/prevenção & controle , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Nanopartículas/química , Traumatismo por Reperfusão/terapia , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Oxirredução , Estresse Oxidativo
12.
Cureus ; 12(7): e9325, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32850203

RESUMO

Metformin is the first-line treatment for any patient with type 2 diabetes. Metformin-associated lactic acidosis and transient blindness have only been reported in some case series and case reports. It is rare and presents especially in patients with underlying chronic kidney disease (CKD) Stage III and above and on high doses of metformin or with a normal dose of metformin and an associated renal injury. We present here a rare and interesting case of something similar. A 77-year-old woman with a past medical history of type 2 diabetes on metformin, obesity status post gastric bypass, CKD Stage III, presented with complaints of nausea, vomiting, confusion, abdominal pain, diarrhea, decreased urine output, sudden visual loss, and a hypoglycemic episode at home. She was hemodynamically stable. Lab work was suggestive of leukocytosis, hyperkalemia, severe high anion gap metabolic and lactic acidosis, acute-on-chronic kidney injury. Findings on the computed tomography (CT) brain, chest radiograph, and CT abdomen and pelvis could not explain the current scenario. She received Ringer's lactate, a bicarbonate push, and an infusion. Acidosis continued to worsen, she became hypotensive requiring pressor support, and she was immediately taken for hemodialysis. All her symptoms, including vision loss, had improved with a single session of hemodialysis, even before the acidosis had corrected. Work-up for other causes of renal dysfunction came back negative. Metformin was discontinued. She was placed on insulin for her diabetes control.

13.
Biomaterials ; 228: 119578, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678843

RESUMO

Hypoxia, resulting from the imbalance between oxygen supply and consumption is a critical component of the tumor microenvironment. It has a paramount impact on cancer growth, metastasis and has long been known as a major obstacle for cancer therapy. However, none of the clinically approved anticancer therapeutics currently available for human use directly tackles this problem. Previous clinical trials of targeting tumor hypoxia with bioreductive prodrugs have failed to demonstrate satisfactory results. Therefore, new ideas are needed to overcome the hypoxia barrier. The method of modulating hypoxia to improve the therapeutic activity is of great interest but remains a considerable challenge. One of the emerging concepts is to supply or generate oxygen at the tumor site to increase the partial oxygen pressure and thereby reverse the hypoxia and its effects. In this review, we present an overview of the recent progress in the development of novel nanomaterials for the alleviation of hypoxic microenvironment. Two main strategies for hypoxia augmentation, i) direct delivery of O2 into the tumor, and ii) in situ O2 generations in the tumor microenvironment through different methods such as catalytic decomposition of endogenous hydrogen peroxide (H2O2) and light-triggered water splitting are discussed in detail. At present, these emerging nanomaterials are in their early phase and expected to grow rapidly in the coming years. Despite the promising start, there are several challenges needed to overcome for successful clinical translation.


Assuntos
Nanoestruturas , Neoplasias , Humanos , Peróxido de Hidrogênio , Hipóxia , Neoplasias/tratamento farmacológico , Hipóxia Tumoral , Microambiente Tumoral
14.
J Control Release ; 326: 442-454, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32726649

RESUMO

Hypoxia is a hallmark of many malignant solid tumors. The inadequate oxygen concentration in the hypoxic regions of a solid tumor impedes the efficiency of photodynamic therapy (PDT) because the generation of reactive oxygen species during the PDT process is directly dependent on the available oxygen. To enhance the therapeutic efficacy of PDT, we have developed a novel catalytic nanoplatform (nGO-hemin-Ce6) by co-encapsulating hemin as a catalase-mimetic nanozyme and chlorin e6 (Ce6) as a photosensitizer into Pluronic-coated nanographene oxide through simple hydrophobic interaction and π-π stacking. The nanosystem showed high cellular uptake in the breast cancer cells but did not show any cytotoxicity in the dark condition. nGO-hemin-Ce6 showed efficient O2 generation capacity in the presence of H2O2, through the catalase-mimetic activity of hemin. In the in vitro cell experiments, only nGO-hemin-Ce6 could show comparable PDT effect in normoxia as well as hypoxia due to the in situ O2 generation capability. Upon intravenous administration, nGO-hemin-Ce6 nanosystem showed high tumor accumulation through passive targeting owing to their small size (~ 50 nm). Within the tumor, hemin generated O2 from the endogenous H2O2 and attenuated hypoxia as evidenced by the reduced expression of HIF-1α, a prominent hypoxia marker. Meanwhile, catalytically generated O2 markedly improved the therapeutic efficiency of PDT in a mouse tumor xenograft model by aiding the light-induced ROS production by Ce6. Compared to a control nanosystem without hemin (nGOCe6), the catalytic nanosystem of nGO-hemin-Ce6 exhibited significantly higher tumor suppression ability.


Assuntos
Fotoquimioterapia , Porfirinas , Animais , Linhagem Celular Tumoral , Hemina , Peróxido de Hidrogênio , Camundongos , Óxidos , Fármacos Fotossensibilizantes
15.
Biomaterials ; 226: 119550, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31645012

RESUMO

Unresolved inflammation is a hallmark of many deadly diseases including atherosclerosis, a silent pathological condition behind majority of cardiovascular diseases. Yet, anti-inflammatory drugs are not clinically used in the treatment of patients with atherosclerosis. The currently approved treatment regimen against atherosclerosis is mainly focused on lowering the cholesterol/lipid levels in blood and has little to do with controlling inflammation, the underlying cause. Recent preclinical and clinical data suggest that effective alleviation of inflammation in the atherosclerosis plaque could reduce the risk of cardiovascular disease. In this work, we have encapsulated interleukin-10 (IL10), a multipotent anti-inflammatory cytokine into cRGD conjugated pluronic based nano-carriers (NC) for targeted delivery to atherosclerotic plaques. The NC could encapsulate the therapeutic protein with a high loading efficiency in a mild condition and showed sustained release capabilities. The efficacy of cytokine encapsulated NC was analyzed in vitro using the lipopolysaccharide stimulated macrophage cells and in vivo using an established apolipoprotein E-knockout (ApoE-/-) C57BL/6 mouse model. Compared to free IL10, intravenous administration of NC encapsulated IL10 resulted in vastly improved pharmacokinetic profile and profoundly high accumulation of the cytokine in the atherosclerosis lesions. IL10 delivered by NC was bioactive and reduced the production of pro-inflammatory cytokine IL-1ß in the lesion and led to significant regression in the plaque size. These results signify the prospect of nanoparticle based cytokine delivery for preventing atherosclerotic through inflammation modulation in near future.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Citocinas , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE
16.
RSC Adv ; 9(26): 15053-15060, 2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35516322

RESUMO

Liposomes with embedded magnetic nanoparticles (magnetoliposomes; MLs) are promising nano-platforms for various biomedical applications. The magnetic behavior of MLs depends on the size of embedded magnetic nanoparticles (MNPs); in general, larger MNPs are more advantageous (e.g. increased magnetic signals). However, the insertion of large MNPs into liposome bilayers is constrained by the thickness of the membrane (∼3.4 nm); thus, the incorporation of larger magnetic nanoparticles (>3.4 nm) into liposomes is a major challenge. We developed a solvent-guided approach for the simple and efficient insertion of large MNPs (6 nm or 15 nm) into the liposomal bilayer. MLs with 6 nm MNPs were used for the magnetic field-guided separation of cancer cells by targeting to human epidermal receptor 2 and folate receptor. We also evaluated the nuclear delivery of oligonucleotides by MLs with a cationic lipid formula. The MLs are expected to be versatile nano-platforms for biomedical applications (e.g. disease diagnosis, therapeutics and cell tracking).

17.
Biomacromolecules ; 9(10): 2905-12, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18785706

RESUMO

In milk caseins exists a natural nanostructure, which can be exploited as a carrier of hydrophobic drugs. Here we investigated the complex formation of curcumin with bovine casein micelles (CMs) and its use as a vehicle for drug delivery to cancer cells. DLS studies of the CM suspension that was stable in buffer solution (pH 7.4) showed an average size distribution of <200 nm. SEM and AFM studies showed that the particles were roughly spherical in shape. Steady-state fluorescence spectroscopy of the CM-curcumin complex formation revealed that curcumin molecules formed complexes with CMs (CM-curcumin complex) through hydrophobic interactions. The binding constant for the CM-curcumin interaction was calculated to be 1.48 x 10(4) M(-1), as determined by the curcumin fluorescence. Fluorescence quenching showed that curcumin molecules quench the intrinsic fluorescence of caseins upon binding. We evaluated the utility of CMs as carriers of curcumin by using in vitro cultured HeLa cells. Cytotoxicity studies of HeLa cells revealed that the IC50 of free curcumin and the CM-curcumin complex was 14.85 and 12.69 microM, respectively.


Assuntos
Caseínas/química , Curcumina/química , Portadores de Fármacos , Micelas , Microscopia de Fluorescência/métodos , Neoplasias/tratamento farmacológico , Sobrevivência Celular , Células HeLa , Humanos , Microscopia de Força Atômica , Modelos Químicos , Conformação Molecular , Nanopartículas/química , Ligação Proteica , Fatores de Tempo
18.
Biomater Sci ; 6(10): 2627-2638, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30109875

RESUMO

The use of injectable materials as a biofiller for soft tissue augmentation has been increasing worldwide. Levan is a biocompatible and inexpensive polysaccharide with great potential in biomaterial applications, but it has not been extensively studied. In this study, we evaluated the potential of levan as a new material for dermal fillers and prepared an injectable and physical levan-based hydrogel by combining levan with Pluronic and carboxymethyl cellulose (CMC). A sol state was prepared by mixing the polymers in a specific ratio at 4 °C for 2 days and the hydrogel was formed by increasing the temperature to 37 °C. The elastic modulus of the levan hydrogel was higher than that of a hyaluronic acid (HA)-based hydrogel. The SEM images of the levan hydrogel showed an interconnected porous structure, similar to the HA hydrogel. Levan showed non-cytotoxicity, enhanced cell proliferation, and higher amount of collagen synthesis in human dermal fibroblast cells compared to HA. The injected levan hydrogel was biocompatible and stable over 2 weeks in vivo, longer than the Pluronic F127 hydrogel or HA hydrogel. Also, the levan hydrogel showed a higher amount of collagen production than the HA hydrogel in vivo. More importantly, the levan hydrogel showed enhanced anti-wrinkle efficacy compared to the HA hydrogel in a wrinkle model mouse. Thus, the levan hydrogel with injectability, biocompatibility, and an anti-wrinkle effect has high potential as an alternative to existing commercial dermal fillers.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Preenchedores Dérmicos/administração & dosagem , Hidrogéis/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Carboximetilcelulose Sódica/administração & dosagem , Carboximetilcelulose Sódica/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colágeno/metabolismo , Preenchedores Dérmicos/química , Fibroblastos/efeitos dos fármacos , Frutanos/administração & dosagem , Frutanos/química , Humanos , Hidrogéis/química , Injeções Subcutâneas , Masculino , Camundongos Pelados , Poloxâmero/administração & dosagem , Poloxâmero/química
19.
Mater Sci Eng C Mater Biol Appl ; 82: 19-24, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29025646

RESUMO

The application of pulsed and continuous wave (CW) lasers in nanomedicine has increased significantly over the last decade. Near infrared (NIR) lasers can be used for the precise control of drug release at the target site in a non-invasive manner. In this study, we have prepared nanographene oxide (nGO, size ~40nm) integrated liposomes (size ~900nm). The nGOs were not simply adsorbed onto the liposome surface but was embedded inside the liposomes as characterized by cryo-TEM, selected area electron diffraction (SAED), and fluorescence quenching studies. The embedded nGOs could act as a molecular switch for NIR light controlled drug release from the liposomes. Calcein was encapsulated into the liposome as a model drug to evaluate the efficiency of light controlled release. An on-demand pulsatile drug release was achieved by irradiation of CW/pulsed NIR lasers into the nGO-liposome suspension. Triggering with a pulsed laser resulted in larger release of calcein with a minimal temperature increase (~2°C) of the liposome solution, compared to lower release rate and a significant temperature increase (~8°C) by a CW laser with the same light energy, suggesting two separate mechanisms and different potential applications depending on the laser type.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ouro/química , Grafite/química , Lipossomos/química , Nanoestruturas/química , Microscopia Crioeletrônica , Fluoresceínas/química , Lipossomos/ultraestrutura , Microscopia Eletrônica de Transmissão
20.
Mater Sci Eng C Mater Biol Appl ; 90: 77-84, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29853148

RESUMO

In situ hydrogel synthesis based on photopolymerization has been recognized as a promising strategy that can be used for tissue augmentation. In this study, we developed an efficient in situ gelation method to prepare bulk hydrogels via near infrared (NIR)-mediated photopolymerization using acrylated polyethylene glycol and diacrylated Pluronic F127-coated upconversion nanoparticles (UCNPs). In our system, upon 980-nm laser irradiation, UCNPs transmit visible light, which triggers the activation of eosin Y to initiate polymerization. We found that the UCNPs coated with diacrylated Pluronic F127 can enhance the photopolymerization efficiency and thus enable the production of bulk hydrogel with requirement of a lower NIR light power compared to that required with the bare UCNPs. This photopolymerization approach will be beneficial to achieve in situ polymerization in vivo for various biomedical applications such as cell/drug delivery and construction of tissue augments.


Assuntos
Hidrogéis/química , Raios Infravermelhos , Nanopartículas/química , Poloxâmero/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Camundongos , Células NIH 3T3 , Polimerização
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