RESUMO
Introduction: Alzheimer's disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy. Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aß1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level. Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H2O2-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-ß deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation. Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.
Assuntos
Doença de Alzheimer , Barreira Hematoencefálica , Cério , Curcumina , Estresse Oxidativo , Zircônio , Animais , Doença de Alzheimer/tratamento farmacológico , Células PC12 , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Zircônio/química , Zircônio/farmacocinética , Camundongos , Ratos , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Curcumina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Cério/química , Cério/farmacocinética , Cério/farmacologia , Cério/administração & dosagem , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Distribuição Tecidual , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Modelos Animais de Doenças , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacocinética , Estruturas Metalorgânicas/farmacologia , Masculino , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismoRESUMO
BACKGROUND: Nano-drug delivery systems have become a promising approach to overcoming problems such as low solubility and cellular uptake of drugs. Along with various delivery devices, dendrimers are widely used through their unique features. PEG-citrate dendrimers are biocompatible and nontoxic, with the ability to improve drug solubility. Curcumin, a naturally occurring polyphenol, has multiple beneficial properties, such as antiviral activities. However, its optimum potential has been significantly hampered due to its poor water solubility, which leads to reduced bioavailability. So, the present study attempted to address this issue and investigate its antiviral effects against HIV-1. METHOD: The G2 PEG-citrate dendrimer was synthesized. Then, curcumin was conjugated to it directly. FTIR, HNMR, DLS, and LCMS characterized the structure of products. The conjugate displayed an intense yellow color. In addition, increased aqueous solubility and cell permeability of curcumin were achieved based on flow cytometry results. So, it could be a suitable vehicle for improving the therapeutic applications of curcumin. Moreover, cell toxicity was assessed using XTT method. Ultimately, the SCR HIV system provided an opportunity to evaluate the level of HIV-1 inhibition by the curcumin-dendrimer conjugate using a p24 HIV ELISA kit. RESULTS: The results demonstrated a 50% up to 90% inhibition of HIV proliferation at 12 µm and 60 µm, respectively. Inhibition of HIV-1 at concentrations much lower than CC50 (300 µM) indicates a high potential of curcumin-dendrimer conjugate against this virus. CONCLUSION: Thereby, curcumin-dendrimer conjugate proves to be a promising tool to use in HIV-1 therapy.
Assuntos
Curcumina , Dendrímeros , Infecções por HIV , HIV-1 , Polietilenoglicóis , Curcumina/farmacologia , Curcumina/química , Dendrímeros/química , Dendrímeros/farmacologia , Humanos , HIV-1/efeitos dos fármacos , Polietilenoglicóis/química , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/química , Ácido Cítrico/química , Nanopartículas/químicaRESUMO
Oral ulcers are a common oral mucosal disease that seriously affect the quality of life. Traditional drug treatments have shown unsatisfactory efficacy and potential adverse reactions. In this study, curcumin-loaded multifunctional magnesium metal-organic framework-embedded hyaluronic acid-soluble microneedles patches were developed to optimize treatment strategies for oral ulcers. This microneedles patch achieves efficient release of curcumin and Mg2+ in the ulcer through precisely targeted delivery and controllable release mechanism, significantly regulates inflammation, promotes cell migration and angiogenesis, and accelerates the ulcer healing process. At the same time, the synergistic effect of curcumin and gallic acid effectively alleviated oxidative stress, while the backplate ε-poly-L-lysine and needle tip Mg2+ jointly constructed an antibacterial barrier to effectively inhibit pathogens. Verification using an oral ulcer rat model showed that the microneedles patch exhibited excellent therapeutic effects. This not only opens up a new avenue for clinical oral treatment but also marks a breakthrough in nanobiomaterials science and drug delivery technology and heralds a broad prospect in the field of oral ulcer treatment in the future.
Assuntos
Curcumina , Sistemas de Liberação de Medicamentos , Magnésio , Estruturas Metalorgânicas , Agulhas , Úlceras Orais , Cicatrização , Curcumina/farmacologia , Curcumina/química , Curcumina/administração & dosagem , Animais , Estruturas Metalorgânicas/química , Úlceras Orais/tratamento farmacológico , Ratos , Cicatrização/efeitos dos fármacos , Magnésio/química , Magnésio/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Ratos Sprague-Dawley , Masculino , Humanos , Ácido Hialurônico/química , Estresse Oxidativo/efeitos dos fármacosRESUMO
BACKGROUND: Ulcerative colitis (UC) is defined by persistent inflammatory processes within the gastrointestinal tract of uncertain etiology. Current therapeutic approaches are limited in their ability to address oxidative stress, inflammation, barrier function restoration, and modulation of gut microbiota in a coordinated manner to maintain intestinal homeostasis. RESULTS: This study involves the construction of a metal-phenolic nanozyme (Cur-Fe) through a ferric ion-mediated oxidative coupling of curcumin. Cur-Fe nanozyme exhibits superoxide dismutase (SOD)-like and â¢OH scavenging activities, demonstrating significant anti-inflammatory and anti-oxidant properties for maintaining intracellular redox balance in vitro. Drawing inspiration from Escherichia coli Nissle 1917 (EcN), a biomimetic Cur-Fe nanozyme (CF@EM) is subsequently developed by integrating Cur-Fe into the EcN membrane (EM) to improve the in vivo targeting ability and therapeutic effectiveness of the Cur-Fe nanozyme. When orally administered, CF@EM demonstrates a strong ability to colonize the inflamed colon and restore intestinal redox balance and barrier function in DSS-induced colitis models. Importantly, CF@EM influences the gut microbiome towards a beneficial state by enhancing bacterial diversity and shifting the compositional structure toward an anti-inflammatory phenotype. Furthermore, analysis of intestinal microbial metabolites supports the notion that the therapeutic efficacy of CF@EM is closely associated with bile acid metabolism. CONCLUSION: Inspired by gut microbes, we have successfully synthesized a biomimetic Cur-Fe nanozyme with the ability to inhibit inflammation and restore intestinal homeostasis. Collectively, without appreciable systemic toxicity, this work provides an unprecedented opportunity for targeted oral nanomedicine in the treatment of ulcerative colitis.
Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Homeostase , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Animais , Homeostase/efeitos dos fármacos , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Curcumina/farmacologia , Curcumina/química , Camundongos Endogâmicos C57BL , Escherichia coli/efeitos dos fármacos , Administração Oral , Biomimética/métodos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
OBJECTIVE: The exacerbation of extreme high-temperature events due to global climate change poses a significant challenge to public health, particularly impacting the central nervous system through heat stroke. This study aims to develop Poly(amidoamine) (PAMAM) nanoparticles loaded with curcumin (PAMAM@Cur) to enhance its therapeutic efficacy in hypothalamic neural damage in a heat stroke model and explore its potential mechanisms. METHODS: Curcumin (Cur) was encapsulated into PAMAM nanoparticles through a hydrophobic interaction method, and various techniques were employed to characterize their physicochemical properties. A heat stroke mouse model was established to monitor body temperature and serum biochemical parameters, conduct behavioral assessments, histological examinations, and biochemical analyses. Transcriptomic and proteomic analyses were performed to investigate the therapeutic mechanisms of PAMAM@Cur, validated in an N2a cell model. RESULTS: PAMAM@Cur demonstrated good stability, photostability, cell compatibility, significant blood-brain barrier (BBB) penetration capability, and effective accumulation in the brain. PAMAM@Cur markedly improved behavioral performance and neural cell structural integrity in heat stroke mice, alleviated inflammatory responses, with superior therapeutic effects compared to Cur or PAMAM alone. Multi-omics analysis revealed that PAMAM@Cur regulated antioxidant defense genes and iron death-related genes, particularly upregulating the PCBP2 protein, stabilizing SLC7A11 and GPX4 mRNA, and reducing iron-dependent cell death. CONCLUSION: By enhancing the drug delivery properties of Cur and modulating molecular pathways relevant to disease treatment, PAMAM@Cur significantly enhances the therapeutic effects against hypothalamic neural damage induced by heat stroke, showcasing the potential of nanotechnology in improving traditional drug efficacy and providing new strategies for future clinical applications. SIGNIFICANCE: This study highlights the outlook of nanotechnology in treating neurological disorders caused by heat stroke, offering a novel therapeutic approach with potential clinical applications.
Assuntos
Curcumina , Golpe de Calor , Nanopartículas , Curcumina/farmacologia , Curcumina/química , Animais , Golpe de Calor/tratamento farmacológico , Camundongos , Nanopartículas/química , Masculino , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/química , Dendrímeros/química , Dendrímeros/farmacologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Linhagem Celular , PoliaminasRESUMO
BACKGROUND: Drug combination therapy is preferred over monotherapy in clinical research to improve therapeutic effects. Developing a new nanodelivery system for cancer drugs can reduce side effects and provide several advantages, including matched pharmacokinetics and potential synergistic activity. This study aimed to examine and determine the efficiency of the gemini surfactants (GSs) as a pH-sensitive polymeric carrier and cell-penetrating agent in cancer cells to achieve dual drug delivery and synergistic effects of curcumin (Cur) combined with tamoxifen citrate (TMX) in the treatment of MCF-7 and MDA-MB-231 human BC cell lines. METHODS: The synthesized NPs were self-assembled using a modified nanoprecipitation method. The functional groups and crystalline form of the nanoformulation were examined by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) used to assess zeta potential and particle size, and the morphological analysis determined by transmission electron microscopy (TEM). The anticancer effect was evaluated through an in vitro cytotoxicity MTT assay, flow cytometry analysis, and apoptosis analysis performed for mechanism investigation. RESULTS: The tailored NPs were developed with a size of 252.3 ± 24.6 nm and zeta potential of 18.2 ± 4.4 mV capable of crossing the membrane of cancer cells. The drug loading and release efficacy assessment showed that the loading of TMX and Cur were 93.84% ± 1.95% and 90.18% ± 0.56%, respectively. In addition, the drug release was more controlled and slower than the free state. Polymeric nanocarriers improved controlled drug release 72.19 ± 2.72% of Tmx and 55.50 ± 2.86% of Cur were released from the Tmx-Cur-Gs NPs after 72 h at pH = 5.5. This confirms the positive effect of polymeric nanocarriers on the controlled drug release mechanism. moreover, the toxicity test showed that combination-drug delivery was much more greater than single-drug delivery in MCF-7 and MDA-MB-231 cell lines. Cellular imaging showed excellent internalization of TMX-Cur-GS NPs in both MCF-7 and MDA-MB-231 cells and synergistic anticancer effects, with combination indices of 0.561 and 0.353, respectively. CONCLUSION: The combined drug delivery system had a greater toxic effect on cell lines than single-drug delivery. The synergistic effect of TMX and Cur with decreasing inhibitory concentrations could be a more promising system for BC-targeted therapy using GS NPs.
Assuntos
Neoplasias da Mama , Curcumina , Nanopartículas , Tensoativos , Tamoxifeno , Humanos , Curcumina/farmacologia , Curcumina/química , Tamoxifeno/farmacologia , Tamoxifeno/química , Nanopartículas/química , Neoplasias da Mama/tratamento farmacológico , Tensoativos/química , Tensoativos/farmacologia , Concentração de Íons de Hidrogênio , Feminino , Sinergismo Farmacológico , Células MCF-7 , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Portadores de Fármacos/químicaRESUMO
A ratiometric fluorescence sensor (Fe-MIL-88-NH2/curcumin) based on luminescent metal-organic frameworks (LMOFs) for the determination of curcumin was constructed. Upon the addition of curcumin, the 535-nm emission of curcumin was enhanced, while the fluorescence emission at 438 nm was quenched, under 367-nm excitation. This sensor demonstrated a broad linear range from 1.5 to 40 µM, a low detection limit of 35 nM, and a fast response time of at most 30 s. We verified the Förster resonance energy transfer (FRET) mechanism between donor (Fe-MIL-88-NH2) and acceptor (curcumin), which further proved the selectivity of the approach. The sensing system enabled the detection of curcumin in the traditional Chinese medicine (TCM) Turmeric. A smartphone-assisted sensing platform was prepared to visually detect curcumin in a portable manner. This study represents the first attempt to fabricate LMOFs for ratiometric fluorescence detection of curcumin, which has promising potential for application in TCM.
Assuntos
Curcumina , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Limite de Detecção , Smartphone , Curcumina/química , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Medicina Tradicional Chinesa , Curcuma/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análiseRESUMO
In the realm of intracellular drug delivery, overcoming the barrier of endosomal entrapment stands as a critical factor influencing the effectiveness of nanodrug delivery systems. This study focuses on the synthesis of an acid-sensitive fatty acid derivative called imidazole-stearic acid (IM-SA). Leveraging the proton sponge effect attributed to imidazole groups, IM-SA was anticipated to play a pivotal role in facilitating endosomal escape. Integrated into the lipid core of solid lipid nanoparticles (SLNs), IM-SA was paired with hyaluronic acid (HA) coating on the surface of SLNs loading with curcumin (CUR). The presence of IM-SA and HA endowed HA-IM-SLNs@CUR with dual functionalities, enabling the promotion of endosomal escape, and specifical targeting of liver cancer. HA-IM-SLNs@CUR exhibited a particle size of â¼228â¯nm, with impressive encapsulation efficiencies (EE) of 87.5â¯% ± 2.3â¯% for CUR. Drugs exhibit significant pH sensitive release behavior. Cellular experiments showed that HA-IM-SLN@CUR exhibits enhanced drug delivery capability. The incorporation of IM-SA significantly improved the endosomal escape of HA-IM-SLN@CUR, facilitating accelerated intracellular drug release and increasing intracellular drug concentration, exhibiting excellent growth inhibitory effects on HepG2 cells. Animal experiments revealed a 3.4-fold increase in CUR uptake at the tumor site with HA-IM-SLNs@CUR over the free CUR, demonstrating remarkable tumor homing potential with the tumor growth inhibition rate of 97.2â¯%. These findings indicated the significant promise of HA-IM-SLNs@CUR in the realm of cancer drug delivery.
Assuntos
Antineoplásicos , Curcumina , Endossomos , Nanopartículas , Tamanho da Partícula , Curcumina/farmacologia , Curcumina/química , Humanos , Nanopartículas/química , Animais , Endossomos/metabolismo , Endossomos/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Células Hep G2 , Liberação Controlada de Fármacos , Camundongos , Lipídeos/química , Sistemas de Liberação de Medicamentos , Proliferação de Células/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Propriedades de Superfície , Portadores de Fármacos/química , Ácidos Esteáricos/química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Imidazóis/química , Imidazóis/farmacologia , Camundongos Nus , Ácido Hialurônico/química , Camundongos Endogâmicos BALB C , LipossomosRESUMO
Curcumin is widely recognized for its health benefits, though the role of gut microbiota in its metabolic transformation was not well studied. In this study, bacterial strains capable of metabolizing curcumin were isolated from human stool samples. Using 16S rRNA and whole-genome sequencing, two novel strains (Clostridium butyricum UMA_cur1 and Escherichia coli UMA_cur2) were identified. In addition, the metabolic products were analyzed using liquid chromatography-mass spectrometry. These strains efficiently converted curcumin into dihydro-curcumin (DHC) and tetrahydro-curcumin (THC). Notably, E. coli UMA_cur2 also produced hexahydro-curcumin (HHC) and octahydro-curcumin (OHC), marking the first identification of a strain capable of such transformations. The absence of the YncB gene (typically involved in curcumin conversion) in C. butyricum UMA_cur1 suggests an alternative metabolic pathway. Curcumin metabolism begins during the stationary growth phase, indicating that it is not crucial for primary growth functions. Furthermore, E. coli UMA_cur2 produced these metabolites sequentially, starting with DHC and THC and progressing to HHC and OHC. These findings identified two novel strains that can metabolize curcumin to hydrogenated metabolites, which enhance our understanding of the interaction between curcumin and gut microbiota.
Assuntos
Curcumina , Escherichia coli , Fezes , Microbioma Gastrointestinal , Humanos , Curcumina/metabolismo , Curcumina/química , Escherichia coli/metabolismo , Escherichia coli/genética , Fezes/microbiologia , Hidrogenação , RNA Ribossômico 16S/genética , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , BiotransformaçãoRESUMO
Iron deficiency anemia (IDA) is a common health issue, and researchers are interested in overcoming it. Nanotechnology green synthesis is one of the recent approaches to making efficient drugs. In this study, we modeled curcumin-coated iron oxide nanoparticles (cur-IONPs) to study their predicted toxicity and drug-likeness properties, then to investigate mucoadhesive behavior by docking cur-IONPs with two main mucin proteins in gastrointestinal tract (GIT) mucosa (muc 5AC and muc 2). Furthermore, the stability of cur-IONPs/protein complexes was assessed by molecular dynamics. Our in-silico studies results showed that cur-IONPs were predicted to be potential candidates to treat IDA due to its mucoadhesive properties, which could enhance the bioavailability, time residency, and iron absorbance through GIT, in addition to its high safety profile with high drug-likeness properties and oral bioavailability. Finally, molecular dynamic simulation studies revealed stable complexes supporting strength docking studies. Our results focus on the high importance of in-silico drug design studies; however, they need to be supported with in vitro and in vivo studies to reveal the efficacy, toxicity, and bioavailability of cur-IONPs.
Assuntos
Anemia Ferropriva , Disponibilidade Biológica , Curcumina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Curcumina/química , Curcumina/farmacocinética , Curcumina/administração & dosagem , Curcumina/farmacologia , Anemia Ferropriva/tratamento farmacológico , Humanos , Administração Oral , Nanopartículas Magnéticas de Óxido de Ferro/química , Ligação ProteicaRESUMO
Overcoming intestinal epithelial barriers to enhance bioavailability is a major challenge for oral delivery systems. Desirable nanocarriers should simultaneously exhibit rapid mucus penetration and efficient epithelial uptake; however, they two generally require contradictory structural properties. Herein, we proposed a strategy to construct multiperformance nanoparticles by modifying the rigidity of amphiphilic nanostructures originating from soy polypeptides (SPNPs), where its ability to overcome multibarriers was examined from both in vitro and in vivo, using curcumin (CUR) as a model cargo. Low-rigidity SPNPs showed higher affinity to mucin and were prone to getting stuck in the mucus layer. When they reached epithelial cells, they tended to be endocytosed through the clathrin and macropinocytosis pathways and further transferred to lysosomes, showing severe degradation and lower transport of CUR. Increased particle rigidity generally improved the absorption of CUR, with medium-rigidity SPNPs bloomed maximum plasma concentration of CUR by 80.62-fold and showed the highest oral bioavailability. Results from monocultured and cocultured cell models demonstrated that medium-rigidity SPNPs were least influenced by the mucus layer and changes in rigidity significantly influenced the endocytosis and intracellular fate of SPNPs. Those with higher rigidity preferred to be endocytosed via a caveolae-mediated pathway and trafficked to the ER and Golgi, facilitating their whole transcytosis, and avoiding intracellular metabolism. Moreover, rigidity modulation efficiently induces the reversible opening of intercellular tight junctions, which synergistically improves the transport of CUR into blood circulation. This study suggested that rigidity regulation on food originated amphiphilic peptides could overcome multiple physiological barriers, showing great potential as natural building block toward oral delivery.
Assuntos
Disponibilidade Biológica , Curcumina , Muco , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Curcumina/metabolismo , Animais , Humanos , Muco/metabolismo , Muco/química , Nanopartículas/química , Nanopartículas/metabolismo , Portadores de Fármacos/química , Células CACO-2 , Tamanho da Partícula , Endocitose , Ratos Sprague-Dawley , Administração Oral , Peptídeos/química , Peptídeos/metabolismo , Camundongos , MasculinoRESUMO
Monoammonium glycyrrhizic acid (MAG), a glycyrrhizic acid monoammonium salt, is a naturally derived low-molecular-weight gelling agent with surface-active properties. It has the capacity to individually facilitate the preparation of gel-solubilized drugs. As MAG is an anionic surfactant with carboxyl groups, the addition of counterions may affect micelle formation and gelation. In this study, the solubilization and gelling properties of MAG were investigated following the addition of metal salts (NaCl and KCl). The addition of metal salts resulted in a decrease in the critical micelle concentration and an increase in gel hardness. Supersaturation of curcumin (CUR) was maintained by the addition of metal salts because of increased micelle number and viscosity. When the gel hardness was compared between formulations with and without CUR, a significant reduction in hardness was observed with the solubilization of CUR. The addition of KCl prevented the decrease in the hardness of gels containing CUR compared to the addition of NaCl. Put together, the addition of metal salts had a noteworthy impact on micelle and gel formation of MAG. In particular, the addition of KCl was more effective in the preparation of gel-solubilized CUR.
Assuntos
Curcumina , Géis , Ácido Glicirrízico , Micelas , Solubilidade , Ácido Glicirrízico/química , Curcumina/química , Géis/química , Cloreto de Sódio/química , Cloreto de Potássio/química , Cátions/química , Viscosidade , Compostos de Amônio Quaternário/químicaRESUMO
Emulsions stabilized via Pickering particles are becoming more and more popular due to their high stability and biocompatibility. Hence, developing new ways to produce effective Pickering particles is essential. In this work, we present a crystal engineering approach to obtain precise control over particle properties such as size, shape, and crystal structure, which may affect wettability and surface chemistry. A highly reproducible synthesis method via anti-solvent crystallization was developed to produce sub-micron sized curcumin crystals of the metastable form III, to be used as Pickering stabilizers. The produced crystals presented a clear hydrophobic nature, which was demonstrated by their preference to stabilize water-in-oil (W/O) emulsions. A comprehensive experimental and computational characterization of curcumin crystals was performed to rationalize their hydrophobic nature. Analytical techniques including Raman spectroscopy, powder X-ray diffraction (PXRD), Solid-State Nuclear Magnetic Resonance (SSNMR), scanning electron microscopy (SEM), Differential Scanning Calorimetry (DSC), confocal fluorescence microscopy and contact angle measurements were used to characterize curcumin particles in terms of shape, size and interfacial activity. The attachment energy model was instead applied to study relevant surface features of curcumin crystals, such as topology and facet-specific surface chemistry. This work contributes to the understanding of the effect of crystal properties on the mechanism of Pickering stabilization, and paves the way for the formulation of innovative products in fields ranging from pharmaceuticals to food science.
Assuntos
Cristalização , Curcumina , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Curcumina/química , Emulsões/química , Difração de Raios X , Microscopia Eletrônica de Varredura , Análise Espectral Raman , Varredura Diferencial de Calorimetria , Molhabilidade , Propriedades de Superfície , Água/química , Espectroscopia de Ressonância MagnéticaRESUMO
BACKGROUND: Curcumin has been used in traditional medicine because of its pharmacological activity, including antioxidant, antibacterial, anticancer, and anticarcinogenic properties. Therefore, sensitive and selective monitoring of curcumin is highly demand for practical application. RESULTS: In this study, we describe the construction of a fluorescence method for curcumin assay based on nitrogen-doped MoS2 quantum dots (N-MoS2 QDs). The N-MoS2 QDs are constructed by a solvothermal method using sodium molybdate and Cys as precursors. With the addition of curcumin, the bright blue fluorescence of N-MoS2 QDs is quenched by the inner filter effect (IFE). The QDs emitted bright blue fluorescence and could be quenched by the addition of curcumin via IFE. The dynamic range is the range of 0.1-10 µM for curcumin detection, with a detection limit of 59 nM. N-MoS2 QDs were applied for curcumin assay in real samples with good recovery. In addition, the N-MoS2 QDs exhibited relative low cytotoxicity and could be applied for fluorescence-based imaging in biological samples. SIGNIFICANCE: Our study indicates that the sensor possesses good selectivity to monitor curcumin in water samples, human urine samples, ginger powder samples, mustard samples, and curry samples with satisfactory recoveries. The N-MoS2 QDs possess less cytotoxicity with excellent biocompatibility and were applied for in vitro cell imaging.
Assuntos
Curcumina , Dissulfetos , Corantes Fluorescentes , Molibdênio , Nitrogênio , Pontos Quânticos , Curcumina/química , Curcumina/farmacologia , Pontos Quânticos/química , Molibdênio/química , Humanos , Dissulfetos/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Nitrogênio/química , Imagem Óptica , Limite de Detecção , Espectrometria de Fluorescência , Sobrevivência Celular/efeitos dos fármacosRESUMO
Concerns about food safety and environmental impact from chemical surfactants have prompted interest in natural lignocellulosic materials as alternatives. In this study, we combined hydrated deep eutectic solvent (DES) pretreatment with ultrasound treatment to prepare lignocellulosic nanofibrils (LCNF) from bamboo shoot shells with appropriate surface properties for stabilizing Pickering emulsions. The pretreatment intensity effectively modulated the surface characteristics of LCNF, achieving desirable wettability through lignin retention and in-situ esterification. The resulting LCNF/curcumin Pickering emulsion (CPE) demonstrated curcumin protection and pH-responsive color changes, while the ensuing CPE/PVA composite film exhibited ultraviolet shielding, mechanical strength, oxygen barrier, and antioxidant properties. Furthermore, the CPE/PVA film showed promise as a real-time indicator for monitoring shrimp freshness, maintaining sensitivity to spoilage even after six months of storage. These findings advance the advancement of green LCNF technologies, providing eco-friendly solutions for valorizing bamboo shoot shells and enhancing the application of LCNF in Pickering emulsions.
Assuntos
Curcumina , Emulsões , Lignina , Nanofibras , Curcumina/química , Lignina/química , Emulsões/química , Animais , Nanofibras/química , Antioxidantes/química , Solventes Eutéticos Profundos/química , Brotos de Planta/química , Sasa/química , Molhabilidade , Concentração de Íons de HidrogênioRESUMO
Multi-aptamer recognition of breast cancer cells (MCF-7) is utilized to achieve high specificity. The method comprises two parts, aptamer-functionalized mesoporous silica nanoparticles (MSNs) loaded with dissimilar dyes (thymolphthalein or curcumin) as signal transducers and aptamer-modified magnetic beads (MBs) as capture agents, which worked together to detect MCF-7 cells sensitively and accurately. The results indicated that the aptasensor has a linear detection range of 100 to 4000 cells and a detection threshold of 10 cells/mL. The method had been successfully employed to detect breast cancer cells in real blood samples to distinguish between breast cancer patients and healthy individuals. In conclusion, the development of the multi-aptamer-based colorimetric sensor offered a novel method for the highly selective detection of MCF-7 cells, contributing to the accurate identification of breast cancer.
Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama , Nanopartículas , Dióxido de Silício , Humanos , Dióxido de Silício/química , Aptâmeros de Nucleotídeos/química , Neoplasias da Mama/sangue , Células MCF-7 , Nanopartículas/química , Porosidade , Feminino , Curcumina/química , Corantes/química , Colorimetria/métodos , Técnicas Biossensoriais/métodos , Limite de DetecçãoRESUMO
The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62% ± 1.09% and a tensile stress of 1.85 ± 0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96 ± 0.08 mIU ml-1, representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1ß, IL-6, TNF-α, IFN-γ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM.
Assuntos
Curcumina , Matriz Extracelular Descelularizada , Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Alicerces Teciduais , Animais , Diabetes Mellitus Tipo 1/terapia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/citologia , Alicerces Teciduais/química , Curcumina/farmacologia , Curcumina/química , Camundongos , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/farmacologia , Suínos , Transplante das Ilhotas Pancreáticas , Cápsulas/química , Insulina/metabolismo , Diabetes Mellitus Experimental/terapia , Linhagem Celular , Matriz Extracelular/metabolismo , Matriz Extracelular/químicaRESUMO
Nanocrystals (NCs) have entirely changed the panorama of hydrophobic drug delivery, showing improved biopharmaceutical performance through multiple administration routes. NCs are potential highly loaded nanovectors due to their pure drug composition, standing out from conventional polymers and lipid nanoparticles that have limited drug-loading capacity. However, research in this area is limited. This study introduces the concept of surface modification of drug NCs through single-layer poly(ethylene glycol) (PEG) polymerization as an innovative strategy to boost targeting efficiency. The postpolymerization analysis revealed size and composition alterations, indicating successful surface engineering of NCs of the model drug curcumin of approximately 200 nm. Interestingly, mucosal tissue penetration analysis showed enhanced entry for fully coated and low cross-linked (LCS) PEG NCs, with an increase of 15 µg/cm2 compared to the control NCs. In addition, we found that polymer chemistry variations on the NCs' surface notably impacted mucin binding, with those armored with LCS PEG showing the most significant reduction in interaction with this glycoprotein. We validated this strategy in an in vitro nose-to-brain model, with all of the NCs exhibiting a promising ability to cross a tight monolayer. Furthermore, the metabolic and pro-inflammatory activity revealed clear indications that, despite surface modifications, the efficacy of curcumin remains unaffected. These findings highlight the potential of surface PEGylated NCs in targeted drug delivery. Altogether, this work sets the baseline for further exploration and optimization of surface polymerized NCs for enhanced drug delivery applications, promising more efficient treatments for specific disorders and conditions requiring active targeting.
Assuntos
Curcumina , Nanopartículas , Polietilenoglicóis , Curcumina/química , Curcumina/farmacologia , Nanopartículas/química , Polietilenoglicóis/química , Humanos , Polimerização , Animais , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Propriedades de Superfície , CamundongosRESUMO
Phytochemicals, plant-derived compounds, are the major components of traditional medicinal plants. Some phytochemicals have restricted applications, due to low bioavailability and less efficacy. However, their medicinal properties can be enhanced by converting them into value-added products for different bioactivities like anti-oxidant, neuroprotective, anti-obesity, anti-neuroinflammatory, anti-microbial, anti-cancer and anti-inflammatory. Microbial transformation is one such process that is generally more specific and makes it possible to modify a compound without making any unwanted alterations in the molecule. This has led to the efficient production of value-added products with important pharmacological properties and the discovery of new active compounds. The present review assimilates the existing knowledge of the microbial transformation of some phytochemicals like eugenol, curcumin, ursolic acid, cinnamaldehyde, piperine, ß-carotene, ß-sitosterol, and quercetin to value-added products for their application in food, fragrances, and pharmaceutical industries.
Assuntos
Compostos Fitoquímicos , Plantas Medicinais , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Eugenol/farmacologia , Ácido Ursólico , Alcaloides/farmacologia , Triterpenos/química , Acroleína/análogos & derivados , Curcumina/química , Curcumina/farmacologia , Biotransformação , Quercetina/química , Alcamidas Poli-Insaturadas , Sitosteroides , Piperidinas , BenzodioxóisRESUMO
A significant health risk arises from the bioaccumulation of harmful Cd (II) in drinking water. Here, we report the unique Cd (II) remediation from drinking water by using novel GO-ZnO-curcumin composite. The composites were tailored by varying the ratio of GO-ZnO and curcumin. The composites followed Langmuir adsorption isotherm and pseudo-second-order kinetics. ZnO nano-rods were more effective in Cd (II) than ZnO nano-disks. A maximum adsorption capacity of 4580 ± 40 mg/gm was achieved for 21G-B with a removal efficiency of 87.5% at neutral pH under optimized conditions. The removal process was governed by ion exchange and electrostatic attraction, followed by cation exchange capacity (CEC). The lattice parameter increase was detected after adsorption of Cd (II) ions. The regeneration and reusability of the composite was studied. Also, the effect of presence of dyes such as methylene blue on Cd (II) adsorption was noted. The latter had negligible effect on Cd (II) removal efficiency from water. The composite showed high antibacterial activity against B. subtilis and P. aeruginosa with minimum inhibitory concentration (MIC) of 10 ± 0.75 µg/ml and 5 ± 1 µg/ml respectively due to the presence of zinc. Composite stability was confirmed through leaching and thermal gravimetric analysis (TGA) analysis. The study establishes the nanocomposite as a potential material for remediation of hazardous Cd (II) ions from real water samples under neutral conditions.