Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.210
Filtrar
1.
ACS Macro Lett ; 13(4): 468-474, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38574471

RESUMO

Glycopolymer-based supramolecular glycoassemblies with signal-driven cascade morphological deformation and accessible surface engineering toward bioinspired functional glycomaterials have attracted much attention due to their diverse applications in fundamental and practical scenarios. Herein, we achieved the cascade morphological transformation and surface engineering of a nucleobase-containing polymeric glycovesicle through exploiting the bioinspired complementary multiple hydrogen bonds of complementary nucleobases. First, the synthesized thymine-containing glycopolymers (PGal30-b-PTAm249) are capable of self-assembling into well-defined glycovesicles. Several kinds of amphiphilic adenine-containing block copolymers with neutral, positive, and negative charges were synthesized to engineer the glycovesicles through the multiple hydrogen bonds between adenine and thymine. A cascade of morphological transformations from vesicles to ruptured vesicles with tails, to worm-like micelles, and finally to spherical micelles were observed via continuously adding the adenine-containing polymer into the thymine-containing glycovesicles. Furthermore, the surface charge properties of these glyconano-objects can be facilely regulated through incorporating various adenine-containing polymers. This work demonstrates the potential application of a unique bioinspired approach to precisely engineer the morphology and surface properties of glycovesicles for boosting their biological applications.


Assuntos
Micelas , Timina , Ligação de Hidrogênio , Polímeros/química , Adenina/química
2.
J Agric Food Chem ; 72(15): 8784-8797, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38566473

RESUMO

Food protein carriers from different sources might have distinct stabilizing and enhancing effects on the same small molecule. To elucidate the molecular mechanism, five different sourced proteins including soy protein isolates (SPIs), whey protein isolates (WPIs), edible dock protein (EDP), Tenebrio molitor protein (TMP), and yeast protein (YP) were used to prepare protein hydrogels for delivering myricetin (Myr). The results suggested that the loading capacity order of Myr in different protein hydrogels was EDP (11.5%) > WPI (9.3%) > TMP (8.9%) > YP (8.0%) > SPI (7.6%), which was consistent with the sequence of binding affinity between Myr and different proteins. Among five protein hydrogels, EDP had an optimum loading ability since it possessed the highest hydrophobic amino acid content (45.52%) and thus provided a broad hydrophobic cavity for loading Myr. In addition, these protein-Myr composite hydrogels displayed the core-shell structure, wherein hydrogen bonding and hydrophobic interaction were the primary binding forces between proteins and Myr. Moreover, the thermal stability, storage stability, and sustained-release properties of Myr were significantly enhanced via these protein delivery systems. These findings can provide scientific guidance for deeper utilization of food alternative protein sources.


Assuntos
Flavonoides , Micelas , Flavonoides/química , Hidrogéis
3.
Drug Deliv ; 31(1): 2337423, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38590120

RESUMO

The present study was designed to develop a self-micellizing solid dispersion (SMSD) containing Thymoquinone (TQM), a phytonutrient obtained from Nigella sativa seeds, aiming to improve its biopharmaceutical and nephroprotective functions. The apparent solubility of TQM in polymer solutions was used to choose an appropriate amphiphilic polymer that could be used to make an SMSD system. Based on the apparent solubility, Soluplus® was selected as an appropriate carrier, and mixing with TQM, SMSD-TQM with different loadings of TQM (5-15%) was made by solvent evaporation and freeze-drying techniques, respectively, and the formulations were optimized. The optimized SMSD-TQM was evaluated in terms of particle size distribution, morphology, release characteristics, pharmacokinetic behavior, and nephroprotective effects in a rat model of acute kidney injury. SMSD-TQM significantly improved the dissolution characteristics (97.8%) of TQM in water within 60 min. Oral administration of SMSD-TQM in rats exhibited a 4.9-fold higher systemic exposure than crystalline TQM. In a cisplatin-induced (6 mg/kg, i.p.) acute kidney-damaged rat model, oral SMSD-TQM (10 mg/kg) improved the nephroprotective effects of TQM based on the results of kidney biomarkers and histological abnormalities. These findings suggest that SMSD-TQM might be efficacious in enhancing the nephroprotective effect of TQM by overcoming biopharmaceutical limitations.


Assuntos
Produtos Biológicos , Micelas , Ratos , Animais , Ratos Sprague-Dawley , Benzoquinonas , Solubilidade , Administração Oral , Disponibilidade Biológica
4.
Oncol Res ; 32(4): 769-784, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560569

RESUMO

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.


Assuntos
Antineoplásicos , Neoplasias Ósseas , Neoplasias da Mama , Poloxaleno , Humanos , Feminino , Micelas , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Ligantes , Qualidade de Vida , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Polímeros/química , Polímeros/uso terapêutico , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Ósseas/tratamento farmacológico , Alendronato/farmacologia , Alendronato/química , Alendronato/uso terapêutico , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico
5.
Int J Nanomedicine ; 19: 3259-3273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601347

RESUMO

Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients. Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed. Results: The developed micelles had a particle size of (89.62 ±1.33) nm and a zeta potential of (-4.9 ±0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ±6.98) µmol/L was significantly lower than that of free Que (141.10 ±6.39) µmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats. Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.


Assuntos
Artrite Experimental , Artrite Reumatoide , Humanos , Ratos , Animais , Metotrexato/química , Micelas , Quercetina/farmacologia , Quercetina/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico
6.
J Mol Graph Model ; 129: 108757, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38503002

RESUMO

The determination of the critical micelle concentration (CMC) is a crucial factor when evaluating surfactants, making it an essential tool in studying the properties of surfactants in various industrial fields. In this present research, we assembled a comprehensive set of 593 different classes of surfactants including, anionic, cationic, nonionic, zwitterionic, and Gemini surfactants to establish a link between their molecular structure and the negative logarithmic value of critical micelle concentration (pCMC) utilizing quantitative structure-property relationship (QSPR) methodologies. Statistical analysis revealed that a set of 14 significant Mordred descriptors (SlogP, GATS6d, nAcid, GATS8dv, GATS4dv, PEOE_VSA11, GATS8d, ATS0p, GATS1d, MATS5p, GATS3d, NdssC, GATS6dv and EState_VSA4), along with temperature, served as appropriate inputs. Different machine learning methods, such as multiple linear regression (MLR), random forest regression (RFR), artificial neural network (ANN), and support vector regression (SVM), were employed in this study to build QSPR models. According to the statistical coefficients of QSPR models, SVR with Dragonfly hyperparameter optimization (SVR-DA) was the most accurate in predicting pCMC values, achieving (R2 = 0.9740, Q2 = 0.9739, r‾m2 = 0.9627, and Δrm2 = 0.0244) for the entire dataset.


Assuntos
Micelas , Odonatos , Animais , Tensoativos/química , Algoritmos , Relação Quantitativa Estrutura-Atividade , Aprendizado de Máquina
7.
J Colloid Interface Sci ; 665: 413-421, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38537589

RESUMO

The essence of compartmentalization in cells is the inspiration behind the engineering of synthetic counterparts, which has emerged as a significant engineering theme. Here, we report the formation of ultra-stable water-in-water (W/W) emulsion droplets. These W/W droplets demonstrate previously unattained stability across a broad pH spectrum and exhibit resilience at temperatures up to 80℃, overcoming the challenge of insufficient robustness in dispersed droplets of aqueous two-phase systems (ATPS). The exceptional robustness is attributed to the strong anchoring of micelle-like casein colloidal particles at the PEO/DEX interface, which maintains stability under varying environmental conditions. The increased surface hydrophobicity of these particles at high temperatures contributes to the formation of thermally-stable droplets, enduring temperatures as high as 80℃. Furthermore, our study illustrates the adaptable affinity of micelle-like casein colloidal particles towards the PEO/DEX-rich phase, enabling the formation of stable DEX-in-PEO emulsions at lower pH levels, and PEO-in-DEX emulsions as the pH rises above the isoelectric point. The robust nature of these W/W emulsions unlocks new possibilities for exploring various biochemical reactions within synthetic subcellular modules and lays a solid foundation for the development of novel biomimetic materials.


Assuntos
Micelas , Resiliência Psicológica , Caseínas , Emulsões , Água , Concentração de Íons de Hidrogênio
8.
ACS Appl Mater Interfaces ; 16(11): 13563-13572, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38449378

RESUMO

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.


Assuntos
Quitosana , Mananas , Quitosana/farmacologia , Hidrogéis/farmacologia , Micelas , Cicatrização , Antibacterianos/farmacologia
9.
Proc Natl Acad Sci U S A ; 121(11): e2307799120, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437544

RESUMO

Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic RNA during delivery to the target tissue and across cellular membrane barriers and then releasing the cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied in lipoplexes and lipid nanoparticles, over medium-sized sequence-defined xenopeptides, to macromolecular polycations applied in polyplexes and polymer micelles. This perspective highlights the discovery of distinct virus-inspired dynamic processes that capitalize on mutual nanoparticle-host interactions to achieve potent RNA delivery. From the host side, subtle alterations of pH, ion concentration, redox potential, presence of specific proteins, receptors, or enzymes are cues, which must be recognized by the RNA nanocarrier via dynamic chemical designs including cleavable bonds, alterable physicochemical properties, and supramolecular assembly-disassembly processes to respond to changing biological microenvironment during delivery.


Assuntos
Sinais (Psicologia) , Micelas , Membrana Celular , Polímeros , RNA
10.
Carbohydr Polym ; 332: 121897, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431408

RESUMO

Cancer multidrug resistance (MDR) dramatically hindered the efficiency of standard chemotherapy. Mitochondria are highly involved in the occurrence and development of MDR; thus, inducing its malfunction will be an appealing strategy to treat MDR tumors. In this paper, a natural polysaccharides-based nanoplatform (TDTD@UA/HA micelles) with cell and mitochondria dual-targeting ability was facilely fabricated to co-deliver ursolic acid (UA) and doxorubicin (DOX) for combinatorial MDR therapy. TDTD@UA/HA micelles featured a spherical morphology, narrow size distribution (∼140 nm), as well as favorable drug co-loading capacity (DOX: 8.41 %, UA: 9.06 %). After hyaluronic acid (HA)-mediated endocytosis, the lysosomal hyaluronidase promoted the degradation of HA layer and then the positive triphenylphosphine groups were exposed, which significantly enhanced the mitochondria-accumulation of nano micelles. Subsequently, DOX and UA were specifically released into mitochondria under the trigger of endogenous reactive oxygen species (ROS), followed by severe mitochondrial destruction through generating ROS, exhausting mitochondrial membrane potential, and blocking energy supply, etc.; ultimately contributing to the susceptibility restoration of MCF-7/ADR cells to chemotherapeutic agents. Importantly, TDTD@UA/HA micelles performed potent anticancer efficacy without distinct toxicity on the MDR tumor-bearing nude mice model. Overall, the versatile nanomedicine represented a new therapeutic paradigm and held great promise in overcoming MDR-related cancer.


Assuntos
Micelas , Neoplasias , Humanos , Animais , Camundongos , 60576 , Ácido Hialurônico/farmacologia , Dextranos/metabolismo , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Resistencia a Medicamentos Antineoplásicos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos , Polímeros/metabolismo , Células MCF-7 , Mitocôndrias , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico
11.
Nanoscale ; 16(12): 6132-6141, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38444355

RESUMO

Thrombosis is the major cause of cardiovascular diseases. Only a small subset of patients could benefit from thrombolytic therapy due to the high bleeding risk brought about by the repeated administration of thrombolytic drugs. Nanoparticles with targeting ligands have been developed as nanocarriers of thrombolytic drugs to deliver the drug to the thrombus through active targeting. However, the passive targeting effect of nanoparticles on the thrombus is yet to be investigated. Herein, we prepared silica cross-linked micelles (SCLMs) with a long blood circulation half-life as drug carriers to target the thrombus through passive targeting. Compared with SCLMs modified with an active targeting ligand cRGD, the SCLMs exhibited similar targeting behavior to the thrombus in vivo. Loaded with the thrombolytic drug tirofiban, the passive targeting SCLMs showed a comparable therapeutic effect to cRGD-modified SCLMs in a mice model with pulmonary embolism and arterial thrombosis.


Assuntos
Nanopartículas , Trombose , Camundongos , Animais , Humanos , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Trombose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Micelas
12.
J Phys Chem B ; 128(11): 2841-2852, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38452254

RESUMO

Polymeric vesicles present great potential in disease treatment as they can be featured as a structurally stable and easily functionalized drug carrier that can simultaneously encapsulate multiple drugs and release them on-demand. Based on the dissipative particle dynamics (DPD) simulation, the drug-loaded vesicles were designed by the co-assembly process of linear amphiphilic triblock copolymers and hydrophobic nanodrugs in solvents, and most importantly, the drug release behavior of drug-loaded vesicles were intensively investigated. The drug-loaded aggregates, such as vesicles, spherical micelles, and disk-like micelles, were observed by varying the size and concentration of nanodrugs and the length of the hydrophobic block. The distribution of nanodrugs in the vesicles was intensively analyzed. As the size of the nanodrugs increases, the localization of nanodrugs change from being unable to fully wrap in the vesicle wall to the uniform distribution and finally to the aggregation in the vesicles at the fixed concentration of nanodrugs. The membrane thickness of the drug-loaded polymeric vesicle can be increased, and the nanodrugs localized closer to the center of the vesicle by increasing the length of the hydrophobic block. The nanodrugs will be released from vesicles by varying the interactions between the nanodrug and the solvent or the hydrophobic block and the solvent, respectively. We found that the release kinetics conforms to the first-order kinetic model, which can be used to fit the cumulative release rate of nanodrugs over time. The results showed that increasing the size of nanodrugs, the length of hydrophobic block, and the interaction parameters between the hydrophobic block and the solvent will slow down the release rate of the nanodrug and change the drug release process from monophasic to biphasic release model.


Assuntos
Micelas , Nanopartículas , Liberação Controlada de Fármacos , Polímeros/química , Portadores de Fármacos/química , Solventes , Interações Hidrofóbicas e Hidrofílicas
13.
Pharm Res ; 41(4): 673-685, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472609

RESUMO

PURPOSE: The purpose of this study was to develop a simulation model for the pharmacokinetics (PK) of drugs undergoing enterohepatic circulation (EHC) with consideration to the environment in the gastrointestinal tract in the fed state in humans. The investigation particularly focused on the necessity of compensating for the permeability rate constant in the reabsorption process in consideration of drug entrapment in bile micelles. METHODS: Meloxicam and ezetimibe were used as model drugs. The extent of the entrapment of drugs inside bile micelles was evaluated using the solubility ratio of Fed State Simulated Intestinal Fluid version 2 (FeSSIF-V2) to Fasted State Simulated Intestinal Fluid version 2 (FaSSIF-V2). Prediction accuracy was evaluated using the Mean Absolute Percentage Error (MAPE) value, calculated from the observed and predicted oral PK profiles. RESULTS: The solubilization of ezetimibe by bile micelles was clearly observed while that of meloxicam was not. Assuming that only drugs in the free fraction of micelles permeate through the intestinal membrane, PK simulation for ezetimibe was performed in both scenarios with and without compensation by the permeation rate constant. The MAPE value of Zetia® tablet, containing ezetimibe, was lower with compensation than without compensation. By contrast, Mobic® tablet, containing meloxicam, showed a relatively low MAPE value even without compensation. CONCLUSION: For drugs which undergo EHC and can be solubilized by bile micelles, compensating for the permeation rate constant in the reabsorption process based on the free fraction ratio appears an important factor in increasing the accuracy of PK profile prediction.


Assuntos
Circulação Êntero-Hepática , Micelas , Humanos , Meloxicam , Solubilidade , Ezetimiba , Comprimidos
14.
Int J Biol Macromol ; 264(Pt 2): 130783, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38471603

RESUMO

Thermosassemble Ionizable Reverse Pluronic (TIRP) platform stands out for its distinctive combination of thermoassemble and ionizable features, effectively overcoming challenges in previous siRNA delivery systems. This study opens up a formation for long-term stabilization, and high loading of siRNA, specifically crafted for targeting oncogenic pathways. TIRP-Bcl2 self-assembles into a unique micelle structure with a nanodiameter of 75.8 ± 5.7 nm, efficiently encapsulating Bcl2 siRNA while maintaining exceptional colloidal stability at 4 °C for 8 months, along with controlled release profiles lasting 180 h. The dual ionizable headgroup enhance the siRNA loading and the revers pluronic unique structural orientation enhance the stability of the siRNA. The thermoassemble of TIRP-Bcl2 facilitates flexi-rigid response to mild hyperthermia, enhancing deep tissue penetration and siRNA release in the tumor microenvironment. This responsive behavior improves intracellular uptake and gene silencing efficacy in cancer cells. TIRP, with its smaller particle size and reverse pluronic nature, efficiently transports siRNA across the blood-brain barrier, holding promise for revolutionizing glioblastoma (GBM) treatment. TIRP-Bcl2 shows significant potential for precise, personalized therapies, promising prolonged siRNA delivery and in vitro/in vivo stability. This research opens avenues for further exploration and clinical translation of this innovative nanocarrier system across different cancers.


Assuntos
Glioblastoma , Nanopartículas , Humanos , RNA Interferente Pequeno/química , Poloxâmero/química , Micelas , Glioblastoma/metabolismo , Inativação Gênica , Linhagem Celular Tumoral , Nanopartículas/química , Microambiente Tumoral
15.
Water Res ; 254: 121384, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479174

RESUMO

Contamination of groundwater by nitrate from intensive agriculture is a serious problem globally. Excessive fertilization has led to nitrate contamination of the Coastal Aquifer in Israel. Here we report the efficient removal of nitrate from contaminated groundwater by micellar-enhanced ultrafiltration (MEUF) using a specially tailored membrane. Graft polymerization with hydrophilic poly(methacrylate) and incorporation of porous zeolitic imidazole framework ZIF-L nanoparticles imparted antifouling properties to the membrane. The resulting modified membrane showed high water permeance (82.2 ± 1.7 L·m-2·h-1·bar-1). The efficiency of nitrate removal by MEUF was tested using cetylpyridinium chloride as a surfactant in nitrate-contaminated groundwater collected from the Coastal Aquifer of Israel. The membrane reduced nitrate levels from 40-70 to levels of 6.8-29.5 mg·L-1, depending on the groundwater composition; further reduction to 6.1-24.1 mg·L-1 with complete surfactant rejection was achieved via two-stage membrane filtration, which showed high permeate flux (between 32.1 ± 0.9 and 45.9 ± 0.6 L·m-2·h-1) at 2 bar. The membrane maintained stable separation performance during multiple cycles, and the flux recovery ratio was >93 %. Nitrate concentrations fell well below the acceptable limit for drinking water, allowing the treated water to be used without restriction. Overall, the membrane has the potential to allow efficient removal by MEUF of nitrate from contaminated groundwater.


Assuntos
Resinas Acrílicas , Água Subterrânea , Poluentes Químicos da Água , Ultrafiltração/métodos , Nitratos/análise , Micelas , Hidrogéis , Poluentes Químicos da Água/análise , Tensoativos , Água
16.
J Colloid Interface Sci ; 664: 338-348, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38479270

RESUMO

Combination therapies demand co-delivery platforms with efficient entrapment of distinct payloads and specific delivery to cells and possibly organelles. Herein, we introduce the combination of two therapeutic modalities, gene and photodynamic therapy, in a purely peptidic platform. The simultaneous formation and cargo loading of the multi-micellar platform is governed by self-assembly at the nanoscale. The multi-micellar architecture of the nanocarrier and the positive charge of its constituent micelles offer controlled dual loading capacity with distinct locations for a hydrophobic photosensitizer (PS) and negatively charged antisense oligonucleotides (ASOs). Moreover, the nuclear localization signal (NLS) sequence built-in the peptide targets PS + ASO-loaded nanocarriers to the nucleus. Breast cancer cells treated with nanocarriers demonstrated photo-triggered enhancement of radical oxygen species (ROS) associated with increased cell death. Besides, delivery of ASO payloads resulted in up to 90 % knockdown of Bcl-2, an inhibitor of apoptosis that is overexpressed in more than half of all human cancers. Simultaneous delivery of PS and ASO elicited synergistic apoptosis to an extent that could not be reached by singly loaded nanocarriers or the free form of the drugs. Both, the distinct location of loaded compounds that prevents them from interfering with each other, and the highly efficient cellular delivery support the great potential of this versatile peptide platform in combination therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oligonucleotídeos Antissenso/farmacologia , Oligonucleotídeos Antissenso/genética , Neoplasias/tratamento farmacológico , Apoptose , Micelas , Linhagem Celular Tumoral
17.
Colloids Surf B Biointerfaces ; 237: 113837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508086

RESUMO

Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0-30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.


Assuntos
Cosmecêuticos , Curcumina , Ratos , Animais , Micelas , Curcumina/farmacologia , Curcumina/química , Antioxidantes/farmacologia , Quercetina/farmacologia , Ratos Wistar , Poloxâmero/química , Polímeros/química , Géis , Portadores de Fármacos/química , Tamanho da Partícula
18.
J Colloid Interface Sci ; 664: 972-979, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508032

RESUMO

HYPOTHESIS: The anticancer drug doxorubicin hydrochloride (DX) shows a high solubility in aqueous media thanks to the positive charge in the ammonium group. This feature, however, affects the drug encapsulation in the hydrophobic domains of polymeric micelles (PMs) used for the targeted delivery of the drug. At basic pH, DX deprotonates but also acquires a negative charge in the phenolic groups of the anthracycline structure. Both the efficiency and the rate of encapsulation will be increased by choosing an appropriate pH such that the drug molecule is in neutral form. EXPERIMENTS: An optimal pH for the encapsulation of the DX in PMs based on commercial poloxamers and on the diblock copolymer methoxy-poly(ethylene glycol)17-b-poly(ε-caprolactone)9 was determined by fluorescence spectroscopy, following the time evolution of both the intensity ratio of the first and the second emission bands of DX and its fluorescence lifetime, both sensitive to the environment polarity. Intracellular delivery of PMs encapsulated drug was followed by Confocal Scanning Laser Microscopy (CSLM). Cell viability was assessed with the sulforhodamine B (SRB) assay. FINDINGS: By adjusting pH to 8.1 a high yield of incorporation of DX in the PMs was achieved coupled to an appreciable increase (one order of magnitude) in the drug encapsulation rate. In-vitro tests in selected cancer cell lines showed the slow release of the drug and a delay in the cytotoxic response in comparison to free DX as detected by CSLM and SRB assay. The proposed methodology paves the way for a greener, faster and more efficient encapsulation of DX in PMs.


Assuntos
Antineoplásicos , Micelas , Poliésteres/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Polímeros/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Polietilenoglicóis/química , Concentração de Íons de Hidrogênio , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos
19.
Colloids Surf B Biointerfaces ; 237: 113871, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38547796

RESUMO

Highly toxic reactive oxygen species (ROS), crucial in inducing apoptosis and ferroptosis, are pivotal for cell death pathways in cancer therapy. However, the effectiveness of ROS-related tumor therapy is impeded by the limited intracellular ROS and substrates, coupled with the presence of abundant ROS scavengers like glutathione (GSH). In this research, we developed acid-responsive, iron-coordinated polymer nanoparticles (PPA/TF) encapsulating a mitochondrial-targeting drug alpha-tocopheryl succinate (α-TOS) for enhanced synergistic tumor treatment. The imidazole grafted micelles exhibit prolonged blood circulation and improve the delivery efficiency of the hydrophobic drug α-TOS. Additionally, PPA's design aids in delivering Fe3+, supplying ample iron ions for chemodynamic therapy (CDT) and ferroptosis through the attachment of imidazole groups to Fe3+. In the tumor's weakly acidic intracellular environment, PPA/TF facilitates pH-responsive drug release. α-TOS specifically targets mitochondria, generating ROS and replenishing those depleted by the Fenton reaction. Moreover, the presence of Fe3+ in PPA/TF amplifies ROS upregulation, promotes GSH depletion, and induces oxidative damage and ferroptosis, effectively inhibiting tumor growth. This research presents an innovative ROS-triggered amplification platform that optimizes CDT and ferroptosis for effective cancer treatment.


Assuntos
Ferroptose , Neoplasias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Micelas , Linhagem Celular Tumoral , Polímeros/química , Neoplasias/patologia , Ferro/química , Concentração de Íons de Hidrogênio , Imidazóis/farmacologia , Peróxido de Hidrogênio/química , Glutationa/metabolismo , Microambiente Tumoral
20.
Int J Pharm ; 655: 124004, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38492899

RESUMO

Photodynamic therapy (PDT) is a suitable alternative to currently employed cancer treatments. However, the hydrophobicity of most photosensitizers (e.g., zinc phthalocyanine (ZnPC)) leads to their aggregation in blood. Moreover, non-specific accumulation in skin and low clearance rate of ZnPC leads to long-lasting skin photosensitization, forcing patients with a short life expectancy to remain indoors. Consequently, the clinical implementation of these photosensitizers is limited. Here, benzyl-poly(ε-caprolactone)-b-poly(ethylene glycol) micelles encapsulating ZnPC (ZnPC-M) were investigated to increase the solubility of ZnPC and its specificity towards cancers cells. Asymmetric flow field-flow fractionation was used to characterize micelles with different ZnPC-to-polymer ratios and their stability in human plasma. The ZnPC-M with the lowest payload (0.2 and 0.4% ZnPC w/w) were the most stable in plasma, exhibiting minimal ZnPC transfer to lipoproteins, and induced the highest phototoxicity in three cancer cell lines. Nanobodies (Nbs) with binding specificity towards hepatocyte growth factor receptor (MET) or epidermal growth factor receptor (EGFR) were conjugated to ZnPC-M to facilitate cell targeting and internalization. MET- and EGFR-targeting micelles enhanced the association and the phototoxicity in cells expressing the target receptor. Altogether, these results indicate that ZnPC-M decorated with Nbs targeting overexpressed proteins on cancer cells may provide a better alternative to currently approved formulations.


Assuntos
Isoindóis , Compostos Organometálicos , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Micelas , Polímeros , Fotoquimioterapia/métodos , Compostos de Zinco , Compostos Organometálicos/farmacologia , Compostos Organometálicos/química , Receptores ErbB , Linhagem Celular Tumoral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...