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1.
Int J Pharm ; 595: 120227, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33484915

RESUMO

In this study, galactosamine-modified poly(ethylene glycol)-poly(lactide) (Gal-PEG-PLA) polymers were synthesized and Gal-PEG-PLA/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles named as GPP micelles were designed to promote the oral absorption of a hydrophobic drug, curcumin (CUR). CUR-loaded Gal-PEG-PLA/TPGS micelles (CUR@GPP micelles) were fabricated using the thin-film dispersion method. CUR@GPP micelles had a size of about 100 nm, a near-neutral zeta potential, drug loading (DL) of 14.6%, and sustained release properties. GPP micelles with high Gal density (GPP3 micelles) were superior in facilitating uptake in epithelial cells and improving intestinal permeation. In situ intestinal absorption studies suggested that the jejunum and ileum were the best absorption segments in the intestinal tract. Additionally, biodistribution results revealed that GPP3 micelles could be remarkably taken up by the jejunum and ileum. Pharmacokinetics revealed that the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from 0 to 24 h (AUC0-24) for CUR@GPP3 micelles were both significantly increased, and that the relative bioavailability of CUR@GPP3 micelles to CUR-loaded mPEG-PLA/TPGS micelles (CUR@PP micelles) was 258.8%. Furthermore, CUR-loaded micelles could reduce damage to the liver and intestinal tissues. This study highlights the importance of Gal content in the design of targeting nanocarrier Gal-modified micelles, which have broad prospects for oral delivery of hydrophobic drugs. Therefore, they could serve as a promising candidate for targeted delivery to the liver.


Assuntos
Curcumina/farmacocinética , Galactosamina/química , Micelas , Polietilenoglicóis/química , alfa-Tocoferol/química , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Curcumina/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Endocitose , Feminino , Humanos , Absorção Intestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Ratos , Solubilidade , Distribuição Tecidual
2.
Food Chem ; 337: 127987, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32927225

RESUMO

Food spoilage is one of the biggest concerns for food safety worldwide. Here, we describe the construction of a carrier for biological agents by chemical combination of porous nanoMOFs and carboxymethylated filter paper (CMFP). When curcumin was encapsulated in nanoMOFs@CMFP, they showed the ability to act as super-long-acting food preserving agents with controllable release of curcumin. Although only 22.3% of curcumin was released into water in 600 h, 65.8% was released into PBS in the same time, and the release into PBS could be tuned by adding citric acid at the time of greatest requirement. Furthermore, the chemical stability of curcumin in nanoMOFs@CMFP was >4.9 times greater than for free curcumin. The outstanding antioxidant and antimicrobial activity of curcumin-loaded nanoMOFs@CMFP paste was demonstrated by prolonging the shelf life of pitayas, which illustrates its potential for development as long-acting and stable preserving paste for use in food preservation.


Assuntos
Antibacterianos/farmacologia , Curcumina/farmacologia , Conservantes de Alimentos/química , Armazenamento de Alimentos , Nanoestruturas/química , Antibacterianos/química , Antibacterianos/farmacocinética , Antioxidantes/química , Antioxidantes/farmacologia , Cactaceae/química , Curcumina/química , Curcumina/farmacocinética , Conservantes de Alimentos/farmacologia , Estruturas Metalorgânicas/química , Testes de Sensibilidade Microbiana , Porosidade
3.
Cancer Sci ; 112(2): 815-827, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33316116

RESUMO

Curcumin has a variety of anticancer properties, but low bioavailability prevents its use in chemotherapeutic applications. To address this problem, we tested the efficacy of the synthetic curcumin analog B14 in breast cancer cells and explored the mechanism by which B14 inhibits proliferation and metastasis of breast cancer cells. We used the breast cancer cell line MCF-7, MDA-MB-231 to study the anticancer effects of B14 and assessed cell viability, cell migration and invasion, cell cycle, and apoptosis, in addition, the antitumor effect of B14 in vivo was examined in mice bearing MDA-MB-231 cells. We found that, as the concentration of B14 increased, cell viability decreased in a dose-dependent manner. Compound B14 exerted the best antitumor activity and selectivity for MCF-7 and MDA-M-231 cells (IC50  = 8.84 µmol/L and 8.33 µmol/L, respectively), while its IC50 value for MCF-10A breast epithelial cells was 34.96 µmol/L. B14 has been shown to be a multi-targeted drug that alters the expression of cyclin D1, cyclin E1, and cyclin-dependent kinase 2 (CDK2), and ultimately induces G1 phase cell cycle arrest. At the same time, B14 activates the mitochondrial apoptosis pathway in breast cancer cells. Furthermore, B14 was more effective than curcumin in inhibiting cell migration, invasion, and colony formation. In tumor-bearing mice, analog B14 significantly reduced tumor growth and inhibited cell proliferation and angiogenesis. The pharmacokinetic test found that B14 was more stable than curcumin in vivo. Our data reveal the therapeutic potential of the curcumin analog B14 and the underlying mechanisms to fight breast cancer cells.


Assuntos
Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Curcumina/análogos & derivados , Curcumina/farmacocinética , Animais , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Food Chem ; 336: 127669, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32758804

RESUMO

Curcumin was recently attracted great interest owing to its multiple bioactivities; however, the use of curcumin was hindered by its poor solubility and stability. In this study, curcumin-nisin-soy soluble polysaccharide nanoparticles (Cur-Nisin-SSPS-NPs, size = 118.76 nm) have been successfully elaborated to improve the application of curcumin. The formation of Cur-Nisin-SSPS-NPs was mediated by amphiphilic and positively charged nisin: SSPS encapsulated nisin, which was mainly driven by electrostatic attraction. And nisin-SSPS complex encapsulated curcumin mainly through hydrophobic interactions between nisin and curcumin. The encapsulation efficiency of curcumin (91.66%) in this novel nanocarriers was significantly higher than that in nanoparticles prepared by a single SSPS (31.82%) or nisin (41.69%), most likely because more hydrophobic regions of nisin were exposed after interacting with SSPS through electrostatic interaction. Consequently, this facile and green nanocarriers improved the solubility/dispersibility and stability of curcumin and nisin, as well as endowed SSPS-based nanoparticles with antioxidant and antimicrobial activities.


Assuntos
Curcumina/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Nisina/química , Polissacarídeos/química , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Curcumina/química , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Imidazóis , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Morfolinas , Solubilidade , Soja/química , Espectrofotometria Ultravioleta
5.
Food Chem ; 340: 127893, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889202

RESUMO

In this work, zein/carboxymethyl dextrin nanoparticles were successfully fabricated at different zein to carboxymethyl dextrin (CMD) mass ratios. Zein/CMD nanoparticles with the negative charge and the smallest size (212 nm) were formed when the mass ratio of zein to CMD was 2:1, exhibiting improved encapsulation efficiency of curcumin (85.5%). Electrostatic interactions, hydrogen bonding and hydrophobic interactions were main driven forces for nanoparticles formulation and curcumin encapsulation. Fourier transform infrared spectroscopy determined curcumin might be partially embedded in CMD during encapsulation. The spherical structures of zein/CMD nanoparticles and curcumin-loaded zein/CMD nanoparticles were observed by transmission electron microscopy. The photothermal stability and antioxidant activity of curcumin were significantly enhanced after be loaded in zein/CMD nanoparticles. Furthermore, encapsulation of curcumin in zein/CMD nanoparticles significantly delayed the release of curcumin in simulated gastrointestinal fluids. These results indicated that zein/CMD nanoparticles could be effective encapsulating materials for bioactive compounds in food industry.


Assuntos
Antioxidantes/química , Curcumina/farmacocinética , Dextrinas/química , Nanopartículas/química , Zeína/química , Antioxidantes/farmacologia , Curcumina/administração & dosagem , Curcumina/química , Preparações de Ação Retardada , Estabilidade de Medicamentos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Nanopartículas/administração & dosagem , Tamanho da Partícula , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Difração de Raios X
6.
Food Chem ; 331: 127281, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32559596

RESUMO

Curcuminoids are the major bioactive constituents of turmeric, the application of which are limited by the poor bioavailability. In this study, turmeric was fermented by the Monascus purpureus and Eurotium cristatum fungi to enhance its bioavailability. To explore the variations in the curcuminoids contents in fermented turmeric, a targeted predict-verify strategy was established. For targeted analysis of curcuminoids, a compound library containing all possible curcuminoids based on their structural skeleton was predicted and built for targeted scanning. Then, the MS data were automatically matched with the predicted library to verify the corresponding curcuminoids. As a result, 115 curcuminoids (48 novel compounds and 14 compounds reported in turmeric for the first time) were fully characterized in crude and fermented turmeric. Among these curcuminoids, 31 were newly generated in fermented turmeric. The established predict-verify strategy allows for an efficient and automatic metabolomic analysis to screen for curcuminoids with potentially better bioavailability.


Assuntos
Curcuma/química , Diarileptanoides/metabolismo , Alimentos e Bebidas Fermentados/análise , Metabolômica/métodos , Disponibilidade Biológica , Curcuma/metabolismo , Curcuma/microbiologia , Curcumina/química , Curcumina/farmacocinética , Diarileptanoides/farmacocinética , Eurotium/metabolismo , Fermentação , Espectrometria de Massas , Monascus/metabolismo , Extratos Vegetais/química , Software
7.
Food Chem ; 326: 126973, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32413757

RESUMO

The aim of this study was to substitute part of soybean phospholipid (SPC) with hydrogenated soybean phospholipid (HSPC) in curcumin-loaded liposomes (Cur-LP), in order to further enhance stability and release performances of curcumin. When the SPC/HSPC mass ratio changed from 10:0 to 5:5, vesicle size, encapsulation efficiency and alkali resistance of curcumin increased, although a small decrease in centrifugal stability was observed. Salt stability became worse as more HSPC was used (3:7 and 0:10). Owing storage at 4 °C and 25 °C, Cur-LP at a SPC/HSPC mass ratio of 5:5 performed well considering vesicle size, lipid oxidation and curcumin retention. These vesicles displayed also the best sustained-release performance in simulated digestion, attributed to the tighter lipid packing in membranes as indicated by fluorescence probes, DSC and FTIR. This study can guide the development of a Cur-LP product with improved shelf-life stability by using HSPC.


Assuntos
Curcumina/farmacocinética , Lipossomos/química , Lipossomos/farmacocinética , Fosfolipídeos/química , Varredura Diferencial de Calorimetria , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Hidrogenação , Lecitinas , Soja/química , Espectroscopia de Infravermelho com Transformada de Fourier
8.
Int J Nanomedicine ; 15: 2987-2998, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431497

RESUMO

Background: Emerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of 99mTc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics. Materials and Methods: The synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice. Results: HA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 µg/mL, compared with free curcumin (77 µg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99mTc. The SPECT images showed that 99mTc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs. Conclusion: The results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99mTc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Curcumina/uso terapêutico , Ácido Hialurônico/química , Nanopartículas/química , Tecnécio/química , Nanomedicina Teranóstica , alfa-Tocoferol/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Curcumina/farmacocinética , Curcumina/farmacologia , Feminino , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polietilenoglicóis/química , Espectroscopia de Prótons por Ressonância Magnética , Distribuição Tecidual/efeitos dos fármacos
9.
Life Sci ; 256: 117840, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32450173

RESUMO

AIMS: Platelet production improvement can resolve concerns about the limitations of external platelet supply and platelet transfusion in thrombocytopenia patients. To this end, scientists encourage to induce the generation of megakaryocyte and platelet. Curcumin is a safe ingredient of turmeric that affects various cellular pathways. The effect of this component on platelet production has not been yet reported. MAIN METHODS: Our in vitro experiments include the investigation of the effects of nanocurcumin on megakaryocytes production from K562 cells and hematopoietic stem cells via megakaryocyte markers expression, DNA content, ROS, and morphologic analysis, and CFC assay. The regulatory functions of MAPKs pathways were also determined. In the in vivo study tissue distribution of nanocurcumin was determined and two treatment schedules were used to evaluate the capability of nanocurcumin to prevent the occurrence of Busulfan-induced thrombocytopenia in the mouse model. KEY FINDING: In vitro evidences demonstrated that nanocurcumin can induce MK production from K562 cells and hematopoietic stem cells. Inhibition of ERK1/2 and JNK pathways arrested this activity. In vivo experiments showed the uptake of nanocurcumin by tissues in mice. Administration of nanocurcumin could preserve bone marrow integrity and increase of the number of circulating platelets in the Busulfan-treated mice models. SIGNIFICANCE: Our results have demonstrated that nanocurcumin administration can be useful for the improvement of megakaryocytes and platelet generation in vitro. This component may be exerting these beneficial effects on megakaryopoiesis by modulating ERK1/2 and JNK pathways. As well as nanocurcumin has the potential to prevent thrombocytopenia in chemotherapy threated mice.


Assuntos
Plaquetas/efeitos dos fármacos , Curcumina/farmacologia , Megacariócitos/efeitos dos fármacos , Nanoestruturas , Trombocitopenia/prevenção & controle , Animais , Antineoplásicos Alquilantes/toxicidade , Plaquetas/metabolismo , Bussulfano/toxicidade , Curcumina/administração & dosagem , Curcumina/farmacocinética , Feminino , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Células K562 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Megacariócitos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Trombocitopenia/induzido quimicamente , Distribuição Tecidual
10.
Sci Rep ; 10(1): 8587, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444829

RESUMO

Systemic toxicity caused by conventional chemotherapy is often regarded as one of the major challenges in the treatment of cancer. Over years, the trigger-based modality has gained much attention as it holds the spatiotemporal control over release and internalization of the drug. In this article, we are reporting an increase in the anti-tumor efficacy of curcumin due to ultrasound pulses. MDA MB 231 breast cancer and B16F10 melanoma cells were incubated with lecithin-based curcumin encapsulated nanoemulsions and exposed to ultrasound in the presence and absence of microbubble. Ultrasound induced sonoporation enhanced the cytotoxicity of curcumin in MDA MB 231 and B16F10 cancer cells in the presence of microbubble by 100- and 64-fold, respectively. To study the spatiotemporal delivery of curcumin, we developed B16F10 melanoma subcutaneous tumor on both the flanks of C57BL/6 mice but only the right tumor was exposed to ultrasound. Insonation of the right tumor spatially enhanced the cytotoxicity and enabled the substantial regression of the right tumor compared to the unexposed left tumor which grew continuously in size. This study showed that the ultrasound has the potential to target and increase the drug's throughput to the tumor and enable effective treatment.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Lecitinas/química , Melanoma Experimental/tratamento farmacológico , Ultrassonografia/métodos , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Curcumina/química , Curcumina/farmacocinética , Feminino , Humanos , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Nanotecnologia , Ratos , Ratos Wistar , Análise Espaço-Temporal , Distribuição Tecidual , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Food Chem ; 319: 126577, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32172044

RESUMO

Many liposoluble nutrients are restricted for applications in foods due to their poor water solubility, stability and bioavailability. Here, a deamidated zein peptide with a broad molecular weight distribution and high carboxyl and hydrophobic residue contents was used to solubilize curcumin. The complex nanoparticles of curcumin and the peptide were produced through self-assembly in aqueous solutions. Fluorescence and infrared spectra revealed that hydrogen bonding and hydrophobic interactions actuated the assembly. The complex nanoparticles had a curcumin loading capacity of 31.9% and completely inhibited curcumin crystallization. The peptide effectively protected curcumin from decomposition in aqueous solutions by inhibiting the reaction between dissolved oxygen and curcumin. The nanoparticles presented excellent freeze-drying/re-dispersion stability without any lyoprotectant. The curcumin bioaccessibility of the nanoparticles was 75% and the nanoparticles exerted a significant antioxidant effect after oral administration in mice. This study indicates that the nanoparticles are potentially useful as an antioxidant additive in foods.


Assuntos
Curcumina/química , Curcumina/farmacocinética , Nanopartículas/química , Zeína/química , Administração Oral , Aminação , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Antioxidantes/farmacocinética , Disponibilidade Biológica , Cristalização , Curcumina/administração & dosagem , Liofilização , Ligação de Hidrogênio , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos Endogâmicos ICR , Estabilidade Proteica , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
12.
J Food Sci ; 85(4): 1292-1301, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32144766

RESUMO

Chemoprevention strategies employing the use of multiple dietary bioactive components and their metabolites in combination offer advantages due to their low toxicity and potential synergistic interactions. Herein, for the first time, we studied the combination of curcumin and 3',4'-didemethylnobiletin (DDMN), a primary metabolite of nobiletin, to determine their combinatory effects in inhibiting growth of human colon cancer cells. Isobologram analysis revealed a synergistic interaction between curcumin and DDMN in the inhibition of cell growth of HCT116 colon cancer cells. The combination treatment induced significant G2 -M cell-cycle arrest and extensive apoptosis, which greatly exceeded the effects of individual treatments with curcumin or DDMN. Proteins associated with these heightened anticarcinogenic effects were p53, p21, HO-1, c-poly(ADP-ribose) polymerase, Cdc2, and Cdc25c; each of the proteins was confirmed to be substantially impacted by the combination treatment, more than by individual treatments alone. Interestingly, an increase in the stability of curcumin was also observed with the presence of DDMN in cell culture medium, which could offer an explanation in part for the synergistic interaction between curcumin and DDMN. This newly identified synergy between curcumin and DDMN should be explored further to determine its chemopreventive potential against colon cancer in vivo. PRACTICAL APPLICATION: This study identifies for the first time the synergistic inhibition of colon cancer cell growth by the dietary component curcumin present in turmeric, in combination with a metabolite of nobiletin, a unique citrus flavonoid. The synergism of the combination may be due to cell-cycle arrest and apoptosis induced by the combination as well as an improvement in the stability of curcumin as a result of the antioxidant property of the nobiletin metabolite. These significant findings of synergism between curcumin and the nobiletin metabolite could offer potential chemopreventive value against colon cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Curcumina/farmacocinética , Flavonas/farmacocinética , Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Curcumina/farmacologia , Sinergismo Farmacológico , Flavonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos
13.
Int J Mol Sci ; 21(6)2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32183162

RESUMO

Worldwide, Alzheimer's disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-ß peptide (Aß42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aß aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Curcumina/análogos & derivados , Fármacos Neuroprotetores/uso terapêutico , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Animais , Curcumina/farmacocinética , Curcumina/uso terapêutico , Desenvolvimento de Medicamentos , Humanos , Fármacos Neuroprotetores/farmacocinética , Ligação Proteica
14.
Cancer Sci ; 111(5): 1785-1793, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32163218

RESUMO

The NF-kappa B (NF-κB) pathway plays a pivotal role in tumor progression and chemoresistance, and its inhibition has been shown to suppress tumor growth in a variety of preclinical models. Recently, we succeeded in synthesizing a water-soluble injectable type of curcumin ß-D-glucuronide (CMG), which is converted into a free-form of curcumin by ß-glucuronidase in vivo. Herein, we aimed to clarify the efficacy, safety and pharmacokinetics of CMG in a xenograft mouse model. First, we confirmed that the presence of KRAS/TP53 mutations significantly increased the IC50 of oxaliplatin (L-OHP) and NF-κB activity in HCT116 cells in vitro. Then, we tested the efficacy of CMG in an HCT116 colon cancer xenograft mice model. CMG demonstrated superior anticancer effects compared to L-OHP in an L-OHP-resistant xenograft model. With regard to safety, significant bodyweight loss, severe myelosuppression and AST/ALT elevation were observed in L-OHP-treated mice, whereas none of these toxicity was noted in CMG-treated mice. The combination of CMG and L-OHP exhibited additive effects in these xenograft models without increasing toxicity. Pharmacokinetic analysis revealed that high levels of free-form curcumin were maintained in the tumor tissue after 48 hours following CMG administration, but it was not detected in other major organs, such as the heart, liver and spleen. Immunohistochemistry revealed reduced NF-κB activity in the tumor tissue extracted from CMG-treated mice compared with that from control mice. These results indicated that CMG could be a promising anticancer prodrug for treating colon cancer with minimal toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Curcumina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glucuronídeos/uso terapêutico , Oxaliplatina/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Curcumina/uso terapêutico , Feminino , Glucuronidase/metabolismo , Glucuronídeos/química , Glucuronídeos/farmacocinética , Glucuronídeos/farmacologia , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Mutação , NF-kappa B/metabolismo , Oxaliplatina/uso terapêutico , Pró-Fármacos , Proteínas Proto-Oncogênicas p21(ras)/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204372

RESUMO

Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.


Assuntos
Células Sanguíneas/química , Curcumina/farmacocinética , Animais , Disponibilidade Biológica , Curcumina/química , Composição de Medicamentos , Humanos , Tamanho da Partícula , Solubilidade , Nanomedicina Teranóstica
16.
Int J Nanomedicine ; 15: 1787-1796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214811

RESUMO

Introduction: Curcumin faces a major challenge in clinical use due to its poor aqueous solubility, which affects its bioavailability over oral use. The present study was carried out to overcome this problem. Methods: An amorphous micellar curcumin-spray dried powder (MC-SDP) with self-assembled casein was prepared by the addition of sucrose as a protectant. The dry powder of curcumin-loaded micelles was obtained by a spray-drying technique in the presence of sucrose as a protectant. The MC-SDP in the form of dry powder was further developed into tablets to investigate the dissolution profile. The physical properties of preformed powder were characterized by differential thermal analysis (DTA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Quantitative analysis in the form of solutions was analyzed by high-performance liquid chromatography (HPLC). Results: The physical properties demonstrated that MC-SDP varies from dented to smoother surfaces as a function of sucrose. Furthermore, melting transitions of curcumin in the form of MC-SDP were broadened in all sample mixtures, as observed in the DTA thermogram. The XRD spectra showed that the sharp and very intense peaks of single curcumin crystalline structure no longer existed in all MC-SDP forms, indicating that the mixtures were amorphous. Moreover, a further dissolution study of MC-SDP showed a significant increase of drug dissolved with the presence of sucrose, where >80% of curcumin from MC-SDP was dissolved within 30 min. Conclusion: The study demonstrated the manufacture of micellar spray-dried powder that would contribute to the development of oral delivery of curcumin.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Administração Oral , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Curcumina/farmacocinética , Composição de Medicamentos , Estabilidade de Medicamentos , Micelas , Microscopia Eletrônica de Varredura , Pós/química , Solubilidade
17.
Food Chem ; 317: 126397, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078994

RESUMO

Curcumin/Hydroxypropyl-beta-Cyclodextrin (HP-ß-CyD) and Curcumin/Hydroxypropyl-gamma-Cyclodextrin (HP-γ-CyD) inclusion complex nanofibrous webs were produced using electrospinning technique for the purpose of orally fast-dissolving antioxidant food supplement. Curcumin was totally preserved without any loss during the electrospinning process. The aqueous solutions of curcumin/HP-ß-CyD and curcumin/HP-γ-CyD were yielded uniform fiber morphology with ~200 nm and ~900 nm average fiber diameter, respectively. Both Curcumin/CyD webs were produced in the form of free-standing and flexible character. Curcumin is a natural bioactive compound with poor water-solubility, however, the phase solubility test and dissolution/disintegration tests (water and artificial saliva) revealed that the water-solubility of curcumin was prominently improved by inclusion complexation with CyD. The antioxidant effect of curcumin in Curcumin/CyD webs was also enhanced due to higher solubility of curcumin by CyD inclusion complex. The results showed that HP-γ-CyD is significantly more effective than HP-ß-CyD in order to enhance the solubility and antioxidant property of curcumin in Curcumin/CyD webs.


Assuntos
Antioxidantes/farmacocinética , Curcumina/farmacocinética , Nanofibras/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Antioxidantes/química , Curcumina/química , Solubilidade , Água , gama-Ciclodextrinas/química
18.
Food Funct ; 11(2): 1684-1691, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32037431

RESUMO

Previous studies have shown that curcumin, a bioactive dietary compound with a thiol-reactive α,ß-unsaturated carbonyl moiety, can covalently modify protein thiols. However, most of the previous studies were performed in cultured cells or cell-free enzyme systems, and so it remains unknown whether curcumin could covalently modify proteins after oral administration in vivo. Using click chemistry-based fluorescence imaging, here we show that oral administration of dialkyne-curcumin (Di-Cur), a "click" probe mimicking curcumin, results in covalent modifications of cellular proteins in colon and liver tissues, but not in other tissues, in mice. This result suggests that oral administration of curcumin leads to the formation of the curcumin-protein complex in a tissue-specific manner, which could contribute to the biological effects and/or pharmacokinetics of curcumin. Further studies to elucidate the identities of curcumin-binding proteins could greatly help us to better understand the molecular mechanisms of curcumin, and develop novel strategies for disease prevention.


Assuntos
Química Click/métodos , Curcumina , Administração Oral , Animais , Linhagem Celular Tumoral , Colo/metabolismo , Curcumina/administração & dosagem , Curcumina/química , Curcumina/metabolismo , Curcumina/farmacocinética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sondas Moleculares , Ligação Proteica , Distribuição Tecidual
19.
Drug Dev Ind Pharm ; 46(3): 412-426, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32011185

RESUMO

Despite poor bioavailability of the drug and in vivo stability, curcumin has been reported for many pharmacological activities. Considering the potential of dendrimers as a drug delivery system, current research work is focused on the formulation and characterization of G4 PAMAM dendrimer-Palmitic acid core-shell nanoparticle-containing curcumin as antistress therapeutics to maximize the bioavailability of curcumin. Various formulations were prepared using different concentrations of palmitic acid and an optimized ratio of dendrimer and curcumin. All formulations were investigated for evaluation of physicochemical parameters, encapsulation efficiency, and in vitro release. Particle size, PDI, zeta-potential, and encapsulation efficiency of final formulation was found to be 257.9 ± 0.365 nm, 0.10 ± 0.004, 3.59 ± 0.167 mV, and 80.87%, respectively. In vitro release studies have shown that 53.62 ± 2.431% of the drug was released after 24 h. In vivo studies pharmacokinetic parameters, drug distribution, pharmacological, and toxicological were also estimated using swiss albino mice. The findings have shown the selected formulation is better than plain curcumin formulation.


Assuntos
Curcumina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas , Animais , Disponibilidade Biológica , Curcumina/química , Curcumina/farmacocinética , Dendrímeros/química , Liberação Controlada de Fármacos , Feminino , Masculino , Camundongos , Nylons/química , Ácido Palmítico/química , Tamanho da Partícula , Distribuição Tecidual
20.
Int J Nanomedicine ; 15: 943-952, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103948

RESUMO

Background: Malignant pleural effusion (MPE) is the accumulation of fluid in the pleural cavity as a result of malignancies affecting the lung, pleura and mediastinal lymph nodes. Curcumin, a compound found in turmeric, has anti-cancer properties that could not only treat MPE accumulation but also reduce cancer burden. To our knowledge, direct administration of curcumin into the pleural cavity has never been reported, neither in animals nor in humans. Purpose: To explore the compartmental distribution, targeted pharmacokinetics and the safety profile of liposomal curcumin following intrapleural and intravenous administration. Methods: Liposomal curcumin (16 mg/kg) was administered into Fischer 344 rats by either intrapleural injection or intravenous infusion. The concentration of curcumin in plasma and tissues (lung, liver and diaphragm) were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Blood and tissues were examined for pathological changes. Results: No pleural or lung pathologies were observed following intrapleural liposomal curcumin administration. Total curcumin concentration peaked 1.5 hrs after the administration of intrapleural liposomal curcumin and red blood cell morphology appeared normal. A red blood cells abnormality (echinocytosis) was observed immediately and at 1.5 hrs after intravenous infusion of liposomal curcumin. Conclusion: These results indicate that liposomal curcumin is safe when administered directly into the pleural cavity and may represent a viable alternative to intravenous infusion in patients with pleural-based tumors.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Cavidade Pleural/efeitos dos fármacos , Administração Intravenosa , Animais , Cromatografia Líquida , Feminino , Lipossomos/administração & dosagem , Lipossomos/farmacocinética , Pulmão/efeitos dos fármacos , Masculino , Neoplasias Pleurais/patologia , Ratos Endogâmicos F344 , Espectrometria de Massas em Tandem , Distribuição Tecidual
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