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1.
Int J Nanomedicine ; 16: 4001-4016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135585

RESUMO

Background: Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy. Methods: Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel "BEL-7402+HUVEC" co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test. Results: The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery. Conclusion: CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Lipossomos/farmacologia , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Ligantes , Lipossomos/administração & dosagem , Lipossomos/química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos Endogâmicos BALB C , Estilbenos/administração & dosagem , Estilbenos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Food Chem ; 362: 130242, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34116430

RESUMO

Construction of nanoscale delivery systems from natural food biopolymer complexes have attracted increasing interests in the fields of food industries. In this study, novel carboxymethyl konjac glucomannan/ chitosan (CMKGM/CS) nanogels with and without 1-ethyl-3-(3-dimethylaminopropyl) /N-hydroxysuccinimide) (EDC/NHS)-initiated crosslinking were prepared. The physicochemical and structural properties of the CMKGM/CS nanogels and their potential to be a delivery vehicle for curcumin were investigated. Compared to original uncrosslinked nanogels, crosslinking did not alter particle size and morphology but decreased zeta potential of nanogels. Fourier transform infrared spectrum confirmed that the amide linkage was formed between CMKGM and CS, which obviously enhanced the stability of crosslinked nanogels under gastrointestinal conditions. Furthermore, the crosslinked nanogels not only had higher encapsulation efficiency of curcumin but also better sustained release behavior under simulated gastrointestinal conditions. These findings suggested that the crosslinked CMKGM/CS nanogels might be a promising delivery system for nutrients.


Assuntos
Quitosana/química , Curcumina/administração & dosagem , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Mananas/química , Nanogéis/química , Tamanho da Partícula
3.
Life Sci ; 277: 119625, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34015288

RESUMO

AIM: Iron oxide nanoparticles (IONPs) have been widely used in diagnosis, drug delivery, and therapy. However, the biodistribution and toxicity profile of IONPs remain debatable and incomplete, thus limiting their further use. We predict that coating iron oxide nanoparticles using curcumin (Cur-IONPs) will provide an advantage for their safety profile. MATERIALS AND METHODS: In this study, an evaluation of the multidose effect (6 doses of 5 mg/kg Cur-IONPs to male BALB/c mice, on alternating days for two weeks) on the toxicity and biodistribution of Cur-IONPs was conducted. KEY FINDINGS: Serum biochemical analysis demonstrated no significant difference in enzyme levels in the liver and kidney between the Cur-IONP-treated and control groups. Blood glucose level measurements showed a nonsignificant change between groups. However, the serum iron concentration was found to initially increase significantly but then decreased at 10 days after the final injection. Histopathological examination of the liver, spleen, kidneys, and brain showed no abnormalities or differences between the Cur-IONP-treated and control groups. There were no abnormal changes in mouse body weight. The biodistribution results showed that Cur-IONPs accumulated mainly in the liver, spleen, and brain, while almost no Cur-IONPs were found in the kidney. The iron content in the liver remained high even 10 days after the final injection, while the iron content in the spleen and brain had returned to normal levels by this time point, indicating their complete clearance. SIGNIFICANCE: These results are significant and promising for the further application of Cur-IONPs as theragnostic nanoparticles.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacologia , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Curcumina/toxicidade , Compostos Férricos/farmacologia , Ferro/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro/química , Nanopartículas de Magnetita/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Baço/efeitos dos fármacos , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
4.
Fish Shellfish Immunol ; 114: 65-81, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33895254

RESUMO

This study aimed to investigate the effectiveness of five natural plant extract compounds Curcumin (CUR); Eugenol (EUG), Cinnamaldehyde (CIN), Stigmasterol (ST) and Morin (MOR), on two species of Saprolegnia; Saprolegnia parasitica and S. australis. Selective compounds were screened for the minimum inhibitory concentration, first for anti-oomycetes activity and then mycelium growth inhibition, spore germination inhibition and colonisation test. Nitric oxide production and myeloperoxidase activity of the compounds were tested in head kidney leukocytes of rainbow trout, Oncorhynchus mykiss to assess the immunostimulatory potential. Molecular docking of effective compounds was carried out with effector proteins of S. parasitica to investigate the target binding sites. Among all, CUR could completely inhibit zoospore production and significantly (p ≤ .05) inhibit hyphal growth at 16 mg l-1 against S. parasitica and S. australis. CIN at the concentration of 50 mg l-1 completely inhibited hyphal growth of both Saprolegnia spp., although the zoospore production of S. parasitica and S. australis was reduced at 25 mg l-1 and 10 mg l-1. In the case of EUG, significant inhibition of the hyphal growth and germination of S. parasitica zoospores was observed at 50 mg l-1. ST and MOR did not show antioomycetes activity. The molecular docking results were consistent with in vitro studies, possibly due to the binding with the vital proteins (Plasma membrane ATPase, V-type proton ATPase, TKL protein kinase, Host targeting protein 1) of S. parasitica and ultimately inhibiting their activity. CUR and CIN showed increased nitric oxide production at the highest concentration of 250 and 256 mg l-1 but the value was not significant (p ≤ .05) with control. CUR showed significantly higher peroxidase activity (p ≤ .05) at a concentration of 256 mg l-1 though values were significantly similar with concentration from 16 to 128 mg l-1. The nitric oxide and total peroxidase activity of rainbow trout leukocytes in the case of CIN showed a significant difference only at 250 mg l-1 against the control. The results conclude that CUR, CIN showed the better anti-Saprolegnia activity and could be used as phyto-additives in aquaculture. Among all, the inclusion of CUR as phyto-additives will provide additional immunostimulatory activity.


Assuntos
Acroleína/análogos & derivados , Curcumina/farmacologia , Eugenol/farmacologia , Extratos Vegetais/farmacologia , Saprolegnia/efeitos dos fármacos , Acroleína/administração & dosagem , Acroleína/química , Acroleína/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/química , Relação Dose-Resposta a Droga , Eugenol/química , Rim Cefálico/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Oncorhynchus mykiss , Extratos Vegetais/química
5.
Int J Nanomedicine ; 16: 2667-2687, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854314

RESUMO

Purpose: The goal was to directly deliver curcumin, a natural polyphenolic anticancer and anti-inflammatory compound, to the lung tissues with minimal systemic exposure through the fabrication of proliposomes, overcoming its poor aqueous solubility and oral bioavailability. Methods: Nano-spray drying was employed to prepare proliposomes using hydroxypropyl beta-cyclodextrin as a carrier. Lecithin and cholesterol were used as lipids, stearylamine and Poloxamer 188 were added as positive charge inducer and a surfactant, respectively. Different characterization parameters were evaluated like percentage yield, entrapment efficiency, drug loading, aerodynamic particle size, in vitro release besides morphological examination. Cytotoxicity studies on cell line A549 lung tumor cells as well as in vivo lung pharmacokinetic studies were also carried. Results: The optimized formulations showed superior aerosolization properties coupled their enhanced ability to reach deep lung tissues with a high % of fine particle fraction. Cytotoxicity studies using MTT assay demonstrated enhanced growth inhibitory effect on lung tumor cells A549 and significant reduction of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6 and interleukin-10 compared to the pure drug. Results of lung pharmacokinetic tests confirmed the superiority of proliposomal curcumin over curcumin powder in both, the rate and extent of lung tissue absorption, as well as the mean residence time within the lung tissues. Conclusion: The pulmonary delivery of curcumin-loaded proliposomes as dry powder provides a direct approach to lung tissues targeting while avoiding the limitations of the oral route and offering a non-invasive alternative to the parenteral one.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Pulmão/efeitos dos fármacos , Secagem por Atomização , Células A549 , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Humanos , Lipossomos , Masculino , Tamanho da Partícula , Poloxâmero/química , Pós , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
6.
Int J Nanomedicine ; 16: 2487-2499, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824587

RESUMO

Purpose: Due to the shortcomings of nanocarriers, the development of carrier-free nanodelivery systems has attracted more and more attention in cancer treatment. However, there are few studies on carrier-free nanosystems that can simultaneously achieve monitoring functions. Here a multifunctional carrier-free nanosystem loaded with curcumin and irinotecan hydrochloride was established for the treatment and monitoring of gastric cancer. Methods: In this study, an irinotecan hydrochloride-curcumin nanosystem in the early stage (the system is named SICN) was prepared. Based on the fluorescence of curcumin, flow cytometry, laser confocal microscopy, and zebrafish fluorescence imaging were used to study the monitoring function of SICN in vivo and in vitro. In addition, HGC-27 human gastric cancer cells were used to study SICN cytotoxicity. Results: Flow cytometry and zebrafish fluorescence imaging monitoring results showed that the uptake of SICN was significantly higher than free curcumin, and the excretion rate was lower. SICN had higher accumulation and retention in cells and zebrafish. Laser confocal microscopy monitoring results showed that SICN was internalized into HGC-27 cells through multiple pathways, including macropinocytosis, caveolin, and clathrin-mediated and clathrin -independent endocytosis, and distributed intracellularly throughout the whole cytoplasm, including lysosomes and Golgi apparatus. In vitro cell experiments showed that SICN nanoparticles were more toxic than single components, and HGC-27 cells had more absorption and higher toxicity to nanoparticles under slightly acidic conditions. Conclusion: SICN is a promising carrier-free nanoparticle, and the combination of two single-component therapies can exert a synergistic antitumor effect. When exposed to a tumor acidic environment, SICN showed stronger cytotoxicity due to charge conversion. More importantly, the nanoparticles' self-monitoring function has been developed, opening up new ideas for combined tumor therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Curcumina/administração & dosagem , Curcumina/farmacologia , Curcumina/uso terapêutico , Portadores de Fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Fluorescência , Humanos , Imageamento Tridimensional , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Tamanho da Partícula , Peixe-Zebra
7.
Int J Nanomedicine ; 16: 1377-1390, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33658778

RESUMO

Background: Vascular drug delivery becomes a promising direction in the development of novel therapeutic strategies in the treatment of cardiovascular pathologies, such as hypertension. However, targeted delivery of hydrophobic substances, with poor bioavailability, remains a challenge. Here, we described the hypotensive effects of a low dose of curcumin delivered to the vascular wall using hyaluronic acid-based nanocapsules. Methods: The group of hypertensive TGR(m-Ren2)27 rats, was administrated respectively with the vehicle, curcumin solution or curcumin delivered using hyaluronic acid-based nanocapsules (HyC12-Cur), for 7 days each, maintaining the wash-out period between treatments. Arterial blood pressure (systolic - SBP, diastolic - DBP) and heart rate (HR) were monitored continuously using a telemetry system (Data Science International), and Mean Arterial Pressure (MAP) was calculated from SBP and DBP. Results: In hypertensive rats, a low dose of curcumin (4.5 mg/kg) administrated in HyC12-Cur for 7 days resulted in a gradual inhibition of SBP, DBP and MAP increase without an effect on HR. At the end of HyC12-Cur - based treatment changes in SBP, DBP and MAP amounted to -2.0±0.8 mmHg, -3.9±0.7 mmHg and -3.3±0.7 mmHg, respectively. In contrast, the administration of a curcumin solution (4.5 mg/kg) did not result in a significant hypotensive effect and the animals constantly developed hypertension. Vascular delivery of capsules with curcumin was confirmed using newly developed fluorine-rich nanocapsules (HyFC10-PFOB) with a shell based on a HA derivative and similar size as HyC12-Cur. HyFC10-PFOB gave fluorine signals in rat aortas analyzed ex vivo with a 19F NMR technique after a single intragastric administration. Conclusion: These results suggest that nanocapsules based on hyaluronic acid, the ubiquitous glycosaminoglycan of the extracellular matrix and an integral part of endothelial glycocalyx, may represent a suitable approach to deliver hydrophobic, poorly bioavailable compounds, to the vascular wall.


Assuntos
Curcumina/administração & dosagem , Curcumina/uso terapêutico , Ácido Hialurônico/química , Hipertensão/tratamento farmacológico , Nanocápsulas/química , Administração Oral , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Pressão Sanguínea/efeitos dos fármacos , Curcumina/farmacologia , Diástole/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flúor/química , Frequência Cardíaca/efeitos dos fármacos , Hidrodinâmica , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/fisiopatologia , Espectroscopia de Ressonância Magnética , Masculino , Tamanho da Partícula , Ratos , Eletricidade Estática , Sístole/efeitos dos fármacos
8.
Nutrients ; 13(2)2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546130

RESUMO

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.


Assuntos
Dieta , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Polifenóis/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Curcumina/administração & dosagem , Suplementos Nutricionais , Modelos Animais de Doenças , Humanos , Camundongos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Polifenóis/química , Resveratrol/administração & dosagem , Silimarina/administração & dosagem
9.
Psychopharmacology (Berl) ; 238(3): 877-886, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33404738

RESUMO

BACKGROUND: Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity. METHODS: Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10 days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1ß, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1ß (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats. CONCLUSION: Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1ß and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity.


Assuntos
Analgésicos/uso terapêutico , Curcumina/uso terapêutico , Hipocampo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Neuralgia/tratamento farmacológico , Memória Espacial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Comportamento Animal/efeitos dos fármacos , Constrição , Curcumina/administração & dosagem , Curcumina/química , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Transtornos da Memória/complicações , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Neuralgia/complicações , Neuralgia/metabolismo , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/lesões
10.
Ann Hematol ; 100(3): 627-633, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33432439

RESUMO

Thalassemia intermedia is a subgroup of ß-thalassemia which originates from mutations in the beta-globin gene. Zinc and copper play important roles in the metabolism. Due to its significant therapeutic effects, curcumin has led many studies to focus on curcumin. In a double-blind clinical trial study, 30 patients with beta-thalassemia intermedia with an age range of 20 to 35 years were randomly selected 1:1 to receive either curcumin or placebo for 3 months. Before and after the intervention period, 5 ml of blood was taken to determine the serum levels of zinc and copper. The laboratory tests were checked at baseline and at the end of the treatment. While the serum levels of zinc and zinc/copper significantly increased, the serum levels of copper decreased after 3 months of curcumin intake. In addition, on the basis of baseline characteristics, a negative correlation was found between zinc and body mass index and positive correlations were identified between copper with triglyceride and high-density lipoprotein. Also, the level of ferritin protein in the curcumin group compared to the placebo group showed a significant decrease after 3 months of curcumin use. Therefore, it could be concluded that curcumin might exert a net protective effect on copper toxicity in thalassemia intermedia patients. The investigation also implicated that curcumin represents an approach to regulating zinc homeostasis and may be useful as a complementary treatment of patients with thalassemia intermedia, especially in patients with zinc deficiency or low serum zinc/copper ratio. Clinical Trial Registration Number: IRCT20190902044668N1.


Assuntos
Cobre/sangue , Curcumina/farmacologia , Zinco/sangue , Talassemia beta/sangue , Administração Oral , Adulto , Análise Química do Sangue , Cápsulas , Cobre/análise , Curcumina/administração & dosagem , Método Duplo-Cego , Ferritinas/análise , Ferritinas/sangue , Humanos , Irã (Geográfico) , Masculino , Adulto Jovem , Zinco/análise , Talassemia beta/tratamento farmacológico
11.
J Mater Chem B ; 9(6): 1604-1615, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-33471012

RESUMO

The therapeutic efficacies of oral nanotherapeutics for ulcerative colitis (UC) are seriously hindered by the lack of mucus-penetrating capacity and uncontrolled drug release. To overcome these limitations, the surface of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) was functionalized with pluronic F127 (PF127), and catalase (CAT)/curcumin (CUR) was co-encapsulated into these NPs. The obtained P-CUR/CAT-NPs had a hydrodynamic particle size of approximately 274.1 nm, narrow size distribution, negative zeta potential (-14.0 mV), and smooth surface morphology. Moreover, the introduction of PF127 to the surface of NPs not only facilitated their mucus penetration, but also improved their cellular uptake efficiency by the target cells (macrophages). We further found that the encapsulation of CAT could remarkably increase the release rate of CUR from NPs in the presence of an H2O2-rich environment. Additionally, P-CUR/CAT-NPs showed the strongest capacity to suppress the secretion of the main pro-inflammatory cytokines, in comparison with their counterparts (CUR-NPs and P-CUR-NPs). Importantly, oral administration of P-CAT/CUR-NPs showed the best therapeutic outcomes than the other NPs. Collectively, these results clearly demonstrate that these mucus-penetrating NPs loaded with CAT and CUR can be exploited as an efficient nanotherapeutic for UC therapy.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Células Cultivadas , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Curcumina/administração & dosagem , Curcumina/química , Liberação Controlada de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície
12.
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
13.
Int J Biol Macromol ; 167: 59-65, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33212103

RESUMO

Newly, the use of biocompatible injectable hydrogel with appropriate features for application in the tissue engineering area as a perfect wound dressing has been more attracted. For this purpose, the curcumin loaded Zein nanoparticles/aldehyde-modified guar gum/silk fibroin (Cur-NPs/OGG/SF) hydrogel networks were successfully developed to increase the Cur bioavailability during the wound treatment procedure. Fabricated hydrogels were assessed for their morphological, thermal stability, degradation, and mechanical features. By varying the OGG/SF weight ratios, the physicochemical features of hydrogels without or with Cur-loaded Zein NPs were studied. The results showed that with enhancing the OGG content, the degradation behavior of hydrogels were improved. Besides, Cur-NPs/OGG/SF hydrogels increased the cell proliferation without any cytotoxic effect on mouse embryonic fibroblast (NIH-3T3) cells. The Cur-NPs/OGG/SF hydrogel exposed inhibition activity against Bacillus (15.26 ± 1.09 mm) and E. coli (11.54± 1.36 mm) bacteria. These achieved results recommended that the novel developed hydrogel could be suitable for wound healing application.


Assuntos
Curcumina/administração & dosagem , Galactanos/química , Hidrogéis/química , Mananas/química , Nanopartículas/química , Gomas Vegetais/química , Zeína/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bombyx , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Fibroínas/química , Camundongos , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Oxirredução , Reologia , Análise Espectral , Termogravimetria , Tecidos Suporte/química
14.
Chem Pharm Bull (Tokyo) ; 69(1): 52-58, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33087639

RESUMO

17ß Hydroxysteroid dehydrogenase type 3 (17ß-HSD3) is the key enzyme in the biosynthesis of testosterone, which is an attractive therapeutic target for prostate cancer (PCa). H10, a novel curcumin analogue, was identified as a potential 17ß-HSD3 inhibitor. The pharmacokinetic study of H10 in rats were performed by intraperitoneal (i.p.), intravenous (i.v.) and oral (p.o.) administration. In addition, the inhibitory effects of H10 against liver CYP3A4 were investigated in vitro using human liver microsomes (HLMs). The acute and chronic toxicological characteristics were characterized using single-dose and 30 d administration. All the mice were alive after i.p. H10 with dose of no more than 100 mg/kg which are nearly the maximum solubility in acute toxicity test. The pharmacokinetic characteristics of H10 fitted with linear dynamics model after single dose. Furthermore, H10 could bioaccumulate in testis, which was the target organ of 17ß-HSD3 inhibitor. H10 distributed highest in spleen, and then in liver both after single and multiple i.p. administration. Moreover, H10 showed weak inhibition towards liver CYP3A4, and did not cause significant changes in aspartate transaminase (AST) and alanine transaminase (ALT) levels after treated with H10 for continuously 30 d. Taken together, these preclinical characteristics laid the foundation for further clinical studies of H10.


Assuntos
17-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Curcumina/farmacologia , Citocromo P-450 CYP3A/metabolismo , Inibidores Enzimáticos/farmacologia , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Curcumina/administração & dosagem , Curcumina/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
15.
Curr Pharm Biotechnol ; 22(5): 622-635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32720599

RESUMO

AIMS: Enhancement of anti-tumor activity of the chemotherapeutic agent CUR by redoxsensitive nanoparticle to get a deeper insight into cancer therapy. BACKGROUND: Tumor targetability and stimulus are widely used to study the delivery of drugs for cancer diagnosis and treatment because poor cellular uptake and inadequate intracellular drug release lead to inefficient delivery of anticancer agents to tumor tissue. OBJECTIVE: Studies distinguishing between tumor and normal tissues or redox-sensitive systems using glutathione (GSH) as a significant signal. METHODS: In this study, we designed Chitosan-Lipoic acid Nanoparticles (CS-LANPs) to improve drug delivery for breast cancer treatment by efficient delivery of Curcumin (CUR). The properties of blank CS-LANPs were studied in detail. The size and the Polydispersity Index (PDI) of the CS-LANPs were optimized. RESULTS: The results indicate the mean size and PDI of the blank CS-LANPs were around 249 nm and 0.125, respectively. However, the Drug Loading (DL) and Encapsulation Efficiency (EE) of the CSLANPs were estimated to be about 18.22% and 99.80%, respectively. Compared to non-reductive conditions, the size of reduction-sensitive CS-LANPs increased significantly under reductive conditions. Therefore, the drug release of CS-LANPs in the presence of glutathione was much faster than that of non-GSH conditions .Moreover, the antitumor effect of CS-LANPs on MCF-7 cells was determined in vitro by MTT assay, cell cytotoxicity, Caspase-3 Assay, detection of mitochondrial membrane potential and quantification of apoptosis incidence. CONCLUSION: CS-LANPs showed a remarkably increased accumulation in tumor cells and had a better tumor inhibitory activity in vitro. CS-LANPs could successfully deliver drugs to cancer cells and revealed better efficiency than free CUR.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Quitosana/química , Curcumina/administração & dosagem , Ácido Tióctico/química , Antineoplásicos Fitogênicos/química , Cápsulas , Caspase 3/análise , Caspase 3/metabolismo , Curcumina/química , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Nanopartículas , Oxirredução
16.
Phytomedicine ; 80: 153356, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33039729

RESUMO

BACKGROUND: Using natural polysaccharides from Traditional Chinese Medicine as nanodrug delivery systems have considerable potential for tumor diagnostics and therapeutics. PURPOSE: On the basis of targeted therapy and combining the advantages of natural polysaccharides (angelica polysaccharide, APS) and natural Chinese medicine (curcumin, Cur) to design functionalized nanoparticles to improve the therapeutic through cell membrane encapsulation and immunotherapy. STUDY DESIGN AND METHODS: Cur-loaded, glycyrrhetic acid (GA)-APS-disulfide bond (DTA)-Cur nanomicelle (GACS-Cur), which were prepared by the dialysis method. GACS-Cur was encapsulated with the membranes from red blood cells (RBCm) termed GACS-Cur@RBCm, which were prepared by the principle of extrusion using a miniature extruder. The developed formulations were subjected to various in vitro and in vivo evaluation tests. RESULTS: The resulting APS nanocarriers supported a favorable drug-loading capacity, biocompatibility, and enhanced synergistic anti-hepatoma effects both in vitro and in vivo. After administration in mice, in vivo imaging results showed that the GACS-Cur and RBCm-coated groups had an obvious stronger tumor tissue targeting ability than the control treatment groups. Additionally, the immunomodulatory effect increased IL-12, TNF-α and IFN-γ expression and CD8+ T cell infiltration (1.9-fold) than that of the saline group. Notably, in comparison with hyaluronic acid (HA) nanocarriers, APS nanocarriers possess higher anti-hepatoma efficiency and targeting capabilities and, thus, should be further studied for a wide range of anti-cancer applications. CONCLUSION: Our data demonstrated that APS nanocarriers encapsulated with erythrocyte membrane mighty be a promising clinical method in the development of efficacy, safety and targeting of liver cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Curcumina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Polissacarídeos/química , Angelica/química , Animais , Antineoplásicos Fitogênicos/imunologia , Antineoplásicos Fitogênicos/farmacologia , Biomimética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Curcumina/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Feminino , Células Hep G2 , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/farmacologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Camundongos Nus , Micelas , Nanopartículas/administração & dosagem , Nanopartículas/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
17.
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
18.
Food Chem ; 337: 128019, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32927227

RESUMO

In this study, the nanocomplexes as a novel delivery system for curcumin, were successfully fabricated using high methoxyl pectin (HMP), individual surfactants (rhamnolipid (Rha), tea saponin (TS) and ethyl lauroyl arginate hydrochloride (ELA)) and pea protein isolate (PPI). The optimum mass ratio between PPI and curcumin was 40:1. The HMP-Rha-PPI-Cur, HMP-TS-PPI-Cur and HMP-ELA-PPI-Cur complexes which had particle sizes of 453, 422 and 587 nm, exhibited encapsulation efficiencies of curcumin with 93.46, 92.05 and 86.73%, respectively. The analysis of FTIR revealed that HMP-surfactant-PPI-Cur complexes were formed mainly by hydrogen bonding and electrostatic attraction. XRD result showed that curcumin exhibited a non-crystallized state in the ternary complexes. Moreover, the curcumin within the HMP-Rha-PPI ternary complexes showed better stability under UV-light, thermal and simulated gastrointestinal conditions.


Assuntos
Curcumina/administração & dosagem , Proteínas de Ervilha/química , Polissacarídeos/química , Tensoativos/química , Curcumina/química , Glicolipídeos , Ligação de Hidrogênio , Modelos Biológicos , Nanopartículas/química , Tamanho da Partícula , Pectinas/química
19.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33179078

RESUMO

Curcumin has a therapeutic effect on ulcerative colitis, but the underlying mechanism has yet to be elucidated. The aim of the present study was to clarify the possible mechanisms. Dextran sulfate sodium­induced colitis mice were treated with curcumin via gavage for 7 days. The effects of curcumin on disease activity index (DAI) and pathological changes of colonic tissue in mice were determined. Interleukin (IL)­6, IL­10, IL­17 and IL­23 expression levels were measured by ELISA. Flow cytometry was used to detect the ratio of mouse spleen regulatory T cells (Treg)/Th17 cells, and western blotting was used to measure the nuclear protein hypoxia inducible factor (HIF)­1α level. The results demonstrated that curcumin can significantly reduce DAI and spleen index scores and improve mucosal inflammation. Curcumin could also regulate the re­equilibration of Treg/Th17. IL­10 level in the colon was significantly increased, while inflammatory cytokines IL­6, IL­17 and IL­23 were significantly reduced following curcumin treatment. No significant difference in HIF­1α was observed between the colitis and the curcumin group. It was concluded that oral administration of curcumin can effectively treat experimental colitis by regulating the re­equilibration of Treg/Th17 and that the regulatory mechanism may be closely related to the IL­23/Th17 pathway. The results of the present study provided molecular insight into the mechanism by which curcumin treats ulcerative colitis.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Curcumina/administração & dosagem , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Administração Oral , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Curcumina/farmacologia , Citocinas/metabolismo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transdução de Sinais/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Resultado do Tratamento
20.
Carbohydr Polym ; 252: 117142, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33183601

RESUMO

The goal of this work was to assess the usability of yeast glucan particles (GPs) as carriers for curcumin and determine the beneficial effect of a pharmacological composite of curcumin in GPs on dextran sulfate sodium induced colitis in rats. The assessment of the anti-inflammatory effect of particular substances was evaluated on the basis of the calculated disease activity index and by assessment of cytokines and enzymes from the gut tissue - tumor necrosis factor α (TNF-α), transforming growth factor ß1, interleukin (IL)-1ß, IL-6, IL-10, IL-17, catalase, superoxide dismutase 2, myeloperoxidase (MPO), and matrix metalloproteinase 9. Composites of GPs with incorporated curcumin showed promising results with the capability to lower symptoms of colitis and significantly decrease the production of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and the activity of MPO, as well. The anti-inflammatory effect of the composites was greater than those of pure GPs or curcumin.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/tratamento farmacológico , Curcumina/uso terapêutico , Portadores de Fármacos/uso terapêutico , Glucanos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Colite/induzido quimicamente , Curcumina/administração & dosagem , Citocinas/metabolismo , Sulfato de Dextrana , Glucanos/administração & dosagem , Interleucinas/metabolismo , Masculino , Ratos , Ratos Wistar , Saccharomyces cerevisiae/metabolismo
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