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1.
Biomed Chromatogr ; 34(2): e4706, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629372

RESUMO

Zhiqiao Gancao (ZQGC) decoction is widely used in China due to its therapeutic effect on lumbar disc herniation (LDH). In this study, we compared the clinical therapeutic effects among oral ZQGC decoction treatment, bed rest, and oral anti-inflammatory drug celecoxib treatment using visual analog scale, Oswestry Disability Index, and MacNab scores. The results showed that ZQGC decoction can significantly improve the symptoms of patients with LDH. A selective, sensitive, and rapid ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of eight bioactive components in rat plasma. The plasma samples were extracted by simple protein precipitation with methanol. The protonated analytes were quantitated simultaneously in positive and negative ion modes by multiple reaction monitoring with a mass spectrometer. The calibration curve of eight components in plasma showed good linearity (r > .996) and the extraction recovery was 81.19% ± 2.15% - 100.39 ± 3.36 (relative standard deviation: 1.21%-10.70%). The accuracy of all the lower limit of quantitation values was quantified within 80%-120%, and the precision was less than 15%. This validated method was successfully applied to the pharmacokinetics study in rat plasma after ZQGC decoction oral treatment. Our research can provide experimental basis for the rational clinical application of ZQGC decoction in the treatment of LDH.


Assuntos
Analgésicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/uso terapêutico , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/sangue , Analgésicos/farmacocinética , Animais , Curcumina/análise , Curcumina/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/análise , Flavonas/sangue , Flavonas/farmacocinética , Ácido Glicirretínico/sangue , Ácido Glicirretínico/farmacocinética , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/fisiopatologia , Deslocamento do Disco Intervertebral/tratamento farmacológico , Deslocamento do Disco Intervertebral/fisiopatologia , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117392, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31330421

RESUMO

Curcumin the extract obtained from the dried rhizome of turmeric, Curcuma longa is a hydrophobic phenol that delivers numerous pharmacological actions like anti-inflammatory, anti-microbial and anti-oxidant, anti-psoriasis, antidiabetic, anticancer. But curcumin has low bioavailability issues that accompany low aqueous solubility, further, when administered orally, >90% of the drug degrades rapidly in the alkaline medium. Administering the drug topically can bypass the problem as well as first-pass metabolism and therefore delivering the drug at the targeted site of action. Encapsulating curcumin in nanostructured lipid nanocarriers (NLC) is an excellent novel strategy. Further, these NLC provides both the controlled release and helps in the enhanced permeation of the drug through the skin's physiological barrier, stratum corneum. For the NLC characterization, a reliable method must be developed that can accurately and precisely determine the drug content in the formulation and also for its in-vitro and ex-vivo characterization. This experiment describes the analytical validation parameters described as per International Conference of Harmonization guidelines to develop a method using the UV-Visible spectroscopy. The method was developed in two solvent systems i.e. methanol and 6.4 pH phosphate buffer with 1.5% polysorbate 80. Methanol solvent was used for the determination of curcumin in the NLC formulation via determining the encapsulation efficiency and 6.4 pH phosphate buffer with 1.5% polysorbate 80 solvent was used for in-vitro and ex-vivo characterization of the developed NLC formulation (cream and gel). These methods were validated in response to linearity, the limit of detection, the limit of quantification, precision, accuracy, repeatability, and specificity.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Espectrofotometria Ultravioleta/métodos , Administração Tópica , Animais , Curcumina/administração & dosagem , Curcumina/farmacocinética , Portadores de Fármacos/administração & dosagem , Cabras , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Pele/química , Pele/metabolismo
3.
Food Chem ; 302: 125328, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31404868

RESUMO

To control the oral bioavailability of curcumin, we fabricated solid lipid nanoparticles (SLNs) using tristearin and polyethylene glycol (PEG)ylated emulsifiers. Lipolysis of prepared SLNs via simulated gastrointestinal digestion was modulated by altering the types and concentrations of emulsifiers. After digestion, the size/surface charge of micelles formed from SLN digesta were predictable and >91% of curcumin was bioaccessible in all of the SLNs. The curcumin permeation rate through mucus-covered gut epithelium in vitro was dependent on the size/surface charge of the micelles. Curcumin loaded in long-PEGylated SLNs rapidly permeated the epithelium due to the neutral surface charge of the micelles, resulting in a >12.0-fold increase in bioavailability compared to curcumin solution in a rat model. These results suggest that the bioavailability of curcumin can be controlled by modulating the interfacial properties of SLNs, which will facilitate the development of curcumin formulations for use in functional foods and pharmaceuticals.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Emulsificantes/química , Nanopartículas/química , Administração Oral , Animais , Disponibilidade Biológica , Células CACO-2 , Digestão , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Humanos , Lipídeos/química , Masculino , Nanopartículas/administração & dosagem , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Triglicerídeos/química
4.
J Photochem Photobiol B ; 199: 111619, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31622787

RESUMO

Curcumin, a naturally derived polyphenolic compound has potent activities against cardiac disease like reducing hypertrophy, increasing antioxidant activity, maintaining hormone levels and blood pressure etc. Polymeric curcumin nanoparticles is a solemn concern nowadays in accordance to improve the beneficial properties of curcumin by diminishing its disadvantages like hydrophobic nature thereby results in maximum delivery of drug curcumin at the target. This study demonstrated the application of curcumin capped gold loaded poly (lactic-co-glycolic acid) nanoparticles (CAu-PLGA Nps) for the inhibition of cardiac hypertrophy by preserving myocardial functions of Wister rat model. Rat models were arbitrarily divided into five groups and observation period was 10 weeks; 1. Control 2. Enalopril (EP), an hypertropic agent induced group 3. EP and Curcumin (C) 4. EP and Curcumin capped gold (CAu) Nps and 5. EP and CAu-PLGA Nps injected group. CAu-PLGA Nps was first synthesized from double emulsion-solvent evaporation method and were characterized by its adoptable techniques such as FT-IR, XRD, SEM and TEM analysis. These analyses demonstrate the encapsulation of curcumin capped gold nanoparticles into PLGA there confirms the successful synthesis of CAu-PLGA Nps. Animals studies illustrates that the CAu-PLGA Nps has significantly produced cardiac anti-hypertrophy and drug delivery when compared to the other groups. CAu-PLGA Nps exhibit increased survival rate, improved cardiac functions like cardiac systolic and diastolic function, maintaining heart weight and left ventricle pressure at the controlled level. Beneficiary activities of CAu-PLGA Nps were associated with its cardiovascular functions like anti-inflammatory, antioxidant, controls cardiomycete growth, increased drug delivery, prevents accumulation of cholesterol and prevents myocardial infarction.


Assuntos
Anti-Inflamatórios não Esteroides/química , Cardiomegalia/tratamento farmacológico , Curcumina/química , Nanopartículas Metálicas/química , Nanocápsulas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Antioxidantes , Terapia Combinada/métodos , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Emulsões/química , Ouro/química , Humanos , Masculino , Tamanho da Partícula , Fototerapia/métodos , Polimerização , Ratos , Solventes/química
5.
Eur J Pharm Sci ; 140: 105070, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518679

RESUMO

Homogeneous PEGylated lipid bilayer coated highly ordered MSNs (PLMSNs) which were systematically optimized and characterized to co-encapsulate paclitaxel (Tax) and curcumin (Cur) were verified to manifest prolonged and enhanced cytotoxic effect against canine breast cancer cells in our previous study. In this article, we took further study of the pharmacokinetic property, cellular uptake, subcellular localization, in vivo distribution and tumor accumulation ability, and treatment efficacy of the drug delivery system. The results revealed that the delivery system could significantly increase the AUC of two drugs, and the anti-tumor effect showed that both intravenous and intratumoral administration group better controlled the tumor weight than that of other groups (P < .05), and the anti-tumor rates were 58.4% and 58.3% respectively. Cell uptake and localization study showed that PLMSNs could effectively carry drugs into cancer cells with sustained release characteristics. The subcellular localization of PLMSNs was mainly in lysosomes and mitochondria. In vivo fluorescence tracing results showed that PLMSNs could be effectively accumulated in the tumor site. The results revealed that the delivery system could effectively reduce the clinical dosage of drugs and reduce its toxic side effects, effectively carry drugs into cancer cells, and exhibit good targeting characteristics for breast cancer.


Assuntos
Antineoplásicos/farmacocinética , Curcumina/farmacocinética , Bicamadas Lipídicas/química , Nanocápsulas/química , Paclitaxel/farmacocinética , Polietilenoglicóis/química , Dióxido de Silício/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Transporte Biológico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/efeitos adversos , Cães , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Quimioterapia Combinada/métodos , Feminino , Humanos , Lisossomos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/metabolismo , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Porosidade , Ratos Sprague-Dawley , Propriedades de Superfície , Carga Tumoral/efeitos dos fármacos
6.
J Endod ; 45(11): 1371-1377, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542283

RESUMO

INTRODUCTION: Curcumin incorporation into polymeric fibers was tested for its antimicrobial properties and potential use in root canal disinfection. METHODS: Curcumin-modified fibers were processed via electrospinning and tested against a 7-day old established Actinomyces naeslundii biofilm. The medicaments tested were as follows: curcumin-modified fibers at 2.5 and 5.0 mg/mL, curcumin-based irrigant at 2.5 and 5.0 mg/mL, saline solution (negative control), and the following positive controls: 2% chlorhexidine, 1% sodium hypochlorite, and triple antibiotic paste (TAP, 1 mg/mL). All medicaments, except for the positive controls, were allocated according to the light exposure protocol (ie, photoactivation with a light-emitting diode every 30 seconds for 4 minutes or without photoactivation). After treatment, the medicaments were removed, and 1 mL saline solution was added; the biofilm was scraped from the well and used to prepare a 1:2000 dilution. Spiral plating was performed using anaerobic blood agar plates. After 24 hours, colony-forming units (colony-forming units/mL, n = 11/group) were counted to determine the antimicrobial effects. RESULTS: Data exhibited significant antimicrobial effects on the positive control groups followed by the curcumin irrigants and, lastly, the photoactivated curcumin-modified fibers. There was a significant reduction of viable bacteria in curcumin-based irrigants, which was greater than the TAP-treated group. Curcumin-free fibers, saline, and the nonphotoactivated curcumin-modified fibers did not display antimicrobial activity. CONCLUSIONS: Curcumin seems to be a potential alternative to TAP when controlling infection, but it requires a minimal concentration (2.5 mg/mL) to be effective. Photoactivation of curcumin-based medicaments seems to be essential to obtain greater antibiofilm activity.


Assuntos
Curcumina , Desinfetantes , Tratamento do Canal Radicular , Actinomyces/efeitos dos fármacos , Biofilmes , Curcumina/farmacocinética , Curcumina/farmacologia , Cavidade Pulpar , Desinfetantes/farmacocinética , Desinfetantes/farmacologia , Desinfecção , Liberação Controlada de Fármacos , Enterococcus faecalis , Irrigantes do Canal Radicular , Hipoclorito de Sódio
7.
Nutrients ; 11(9)2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509968

RESUMO

Curcumin is a compound isolated from turmeric, a plant known for its medicinal use. Recently, there is a growing interest in the medical community in identifying novel, low-cost, safe molecules that may be used in the treatment of inflammatory and neoplastic diseases. An increasing amount of evidence suggests that curcumin may represent an effective agent in the treatment of several skin conditions. We examined the most relevant in vitro and in vivo studies published to date regarding the use of curcumin in inflammatory, neoplastic, and infectious skin diseases, providing information on its bioavailability and safety profile. Moreover, we performed a computational analysis about curcumin's interaction towards the major enzymatic targets identified in the literature. Our results suggest that curcumin may represent a low-cost, well-tolerated, effective agent in the treatment of skin diseases. However, bypass of limitations of its in vivo use (low oral bioavailability, metabolism) is essential in order to conduct larger clinical trials that could confirm these observations. The possible use of curcumin in combination with traditional drugs and the formulations of novel delivery systems represent a very promising field for future applicative research.


Assuntos
Curcumina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Animais , Curcumina/efeitos adversos , Curcumina/farmacocinética , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacocinética , Humanos , Pele/metabolismo , Pele/patologia , Dermatopatias/metabolismo , Dermatopatias/patologia , Resultado do Tratamento
8.
Colloids Surf B Biointerfaces ; 182: 110405, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377611

RESUMO

Tumor cells are sensitive to the disturbance of mitochondrial functions. Attenuation of dysfunctional mitochondria by natural compounds is an emerging strategy for the recovery of abnormal energy metabolism of cancer. To develop a nano-sized curcumin (CUR) in attenuating the energy metabolism of cancer cells, herein, a coral-shaped nano-transporter DNA-FeS2-DA nanoparticle was synthesized using double-stranded DNA rich in 'GAG' and 'GC' series as a template and poly-dopamine as an adhesive. CUR was successfully loaded to DNA-FeS2-DA with a molar ratio of ssDNA: CUR of 1:16, forming CUR@DNA-FeS2-DA. This nano-curcumin can readily enter mitochondrion in MCF-7 cancer cells. The CUR@DNA-FeS2-DA nanocomposite displays desirable photothermal effect and stability, while its CUR can be released gradually in the weak acid environment. The expression of both pyruvate kinase M2 and fatty acid synthase in the MCF-7 cancer cells were noticeably inhibited by CUR@DNA-FeS2-DA. Given the controlled release and mitochondria-targeting properties, this CUR@DNA-FeS2-DA nanocomposite is a promising new drug entity for intervening the energy metabolism of cancer cells.


Assuntos
Curcumina/farmacologia , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Piruvato Quinase/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/farmacocinética , DNA/química , Dopamina/química , Liberação Controlada de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Ácido Graxo Sintase Tipo I/metabolismo , Humanos , Ferro/química , Células MCF-7 , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Piruvato Quinase/metabolismo , Sulfetos/química
9.
Molecules ; 24(14)2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31373330

RESUMO

Zein composite particles coated with caseinate-pectin electrostatic complexes (zein-caseinate-pectin particles) were fabricated using an electrostatic deposition and liquid-liquid dispersion method without heating treatment. Compared to zein particles coated only with caseinate, the acidic stability of zein-caseinate-pectin particles was greatly improved, and the particle aggregation was suppressed at pH 3-6, especially at pH values near the isoelectric point of caseinate (pH 4-5). Besides, desirable long-term storage stability and re-dispersibility were observed. Under different zein to curcumin (Cur) feeding ratios (10:1, 20:1, 30:1 and 40:1, w/w), the Cur-loaded zein-caseinate-pectin particles had a spherical shape with an average diameter ranging from 358.37 to 369.20 nm, a narrow size distribution (polydispersity index < 0.2) and a negative surface charge ranging from -18.87 to -19.53 mV. The relatively high encapsulation efficiencies of Cur (81.27% to 94.00%) and desirable re-dispersibility were also achieved. Fluorescence spectroscopy indicated that the encapsulated Cur interacted with carrier materials mainly through hydrophobic interactions. The in-vitro release profile showed a sustained release of Cur from zein-caseinate-pectin particles in acidic aqueous environment (pH 4) up to 24 h, without any burst effect. In addition, the encapsulation retained more ABTS•+ radical scavenging capacity of Cur during 4 weeks of storage. These results suggest that zein-caseinate-pectin particles may be used as a potential delivery system for lipophilic nutrients in acidic beverages.


Assuntos
Caseínas , Curcumina , Nanopartículas/química , Pectinas , Zeína , Cápsulas , Caseínas/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Pectinas/química , Pectinas/farmacocinética , Eletricidade Estática , Zeína/química , Zeína/farmacocinética
10.
Int J Nanomedicine ; 14: 5477-5490, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409999

RESUMO

Background: Curcumin, a bioactive component with multiple characteristics, has been shown to have many therapeutic effects. However, there are several limitations regarding the use of curcumin such as instability, low solubility, poor bioavailability, and rapid elimination. Different approaches have been used to solve these problems. Materials and methods: In this study, surface-modified nanosuspension (NS) is investigated as a novel brain delivery system. Two different methods were used for the preparation of nanosuspensions with two different stabilizers. The surface of the nanosuspensions was coated with D-α-tocopheryl polyethylene glycol 1,000 succinate (TPGS) and Tween 80 using physical adsorption. Curcumin NSs were prepared using two different top-down techniques by high-pressure homogenizer and probe sonicator. A validated sensitive and selective high-performance liquid chromatography method using fluorescence detection was used for the determination and quantification of curcumin. Pharmacokinetics and biodistribution of curcumin NSs and solutions after intravenous administration in rats were studied. Results: Higher levels of curcumin in the brain were detected when Tween 80-coated NS was used compared with the curcumin solution and TPGS coated NS (TPGS-NS) (P-value<0.05). Absorption of ApoE and/or B by Tween 80-coated nanoparticles (NPs) from the blood were caused transferring of these NPs into the brain using receptor-mediated endocytosis. Distribution of TPGS-NS in the brain compared with the curcumin solution was higher (P-value<0.05). Higher levels of curcumin concentration in the liver, spleen, and lung were also observed with TPGS-NS. Conclusion: The results of this study indicate that the surface-coating of NSs by Tween 80 may be used to improve the biodistribution of curcumin in the brain.


Assuntos
Encéfalo/metabolismo , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Suspensões/química , Administração Intravenosa , Animais , Disponibilidade Biológica , Curcumina/farmacocinética , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Wistar , Distribuição Tecidual , Vitamina E/química
11.
J Colloid Interface Sci ; 556: 128-139, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31437658

RESUMO

Magnetic drug delivery system is one of the most important strategies for cancer diagnosis and treatment. In this study, a novel theranostic system was fabricated based on cyclodextrin nanosponge (CDNS) polymer anchored on the surface of Magnetite nanoparticles (Fe3O4/CDNS NPs) which was then decorated with folic acid (FA) as a targeting agent (Fe3O4/CDNS-FA). Curcumin (CUR), a hydrophobic model drug, was next loaded into the cyclodextrin cavity and polymeric matrix of CDNS (Fe3O4/CDNS-FA@CUR). The system was fully characterized. The in vitro release study revealed pH-sensitive behavior. Cytotoxicity assays indicated a negligible toxicity for CUR free Fe3O4/CDNS-FA NPs against both of M109 cancerous cells and MCF 10A normal cells. CUR-loaded Fe3O4/CDNS-FA NPs exhibited higher toxicity against M109 cancerous cells than MCF 10A normal cells (p < 0.05). Fe3O4/CDNS-FA@CUR NPs resulted in much more cell viability on normal cells than pure CUR (p < 0.05). Moreover, blood compatibility study showed minor hemolytic activity. In vitro MRI studies illustrated negative signal increase in cells affirming acceptable diagnostic ability of the nanocarrier. The T2 MR signal intensity for Fe3O4/CDNS-FA@CUR NPs in M109 cells was around 2-fold higher than that of MCF 10A cells. This implies two times higher selective cellular uptake of the Fe3O4/CDNS-FA@CUR NPs into M109 cell compared to MCF 10A. The multifunctional nanocarrier could be considered as promising candidate for cancer theranostics because of the smart drug release, selective cytotoxicity, suitable hemocompatibility, and proper T2 MRI contrast efficiency.


Assuntos
Materiais Revestidos Biocompatíveis , Meios de Contraste , Curcumina , Sistemas de Liberação de Medicamentos , Ácido Fólico , Imagem por Ressonância Magnética , Nanopartículas de Magnetita , Neoplasias , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacocinética , Materiais Revestidos Biocompatíveis/farmacologia , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Ácido Fólico/química , Ácido Fólico/farmacocinética , Ácido Fólico/farmacologia , Humanos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
12.
J Food Sci ; 84(9): 2584-2591, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31436860

RESUMO

The potential of heterogeneous systems like oil-in-water (O/W) nanoemulsions is exploited as an oral delivery system for curcumin, a natural lipophilic compound with numerous health benefits. Two types of O/W nanoemulsions, one stabilized by sodium caseinate (Cas-O/W), a surface-active and emulsifying protein, and the other stabilized by a blend of caseinate and Tween 20 (Mix-O/W), were loaded with the bioactive compound and tested through a simulated gastrointestinal digestion process to evaluate their effects on delivering of curcumin. It was first demonstrated that the amount of curcumin solubilized through Mix-O/W nanoemulsion was higher than that in Cas-O/W nanoemulsion. Cas-O/W nanoemulsions, indeed, at their best, solubilized about 55 µg/mL of curcumin while Mix-O/W nanoemulsions reached a curcumin concentration around 180 µg/mL. Furthermore, for both the systems an increase of curcumin loading capacity was recorded with the rise of incubation temperature. Finally, after the in vitro simulated digestion process, the potential curcumin bioavailability was evaluated and the data suggested that Mix-O/W nanoemulsions provided more than twice the amount of curcumin compared to Cas-O/W nanoemulsions. On balance, the outcomes of this investigation demonstrated that the mixed emulsifier system offered a higher amount of lipophilic compound with a low fat intake compared to nanoemulsions stabilized by sodium caseinate. PRACTICAL APPLICATION: The outcomes of this study allow the recognition of the protein/surfactant-stabilized nanoemulsions as a suitable solution to deliver curcumin. The nanoemulsions proposed here provide a high intake of curcumin, a lipophilic compound, with low fat content. The use of such delivery systems helps to overcome limits in oral bioavailability related with the scarce solubility of some compounds in food preparations and beverages.


Assuntos
Caseínas/química , Curcumina , Emulsões/química , Nanopartículas/química , Tensoativos/química , Disponibilidade Biológica , Curcumina/química , Curcumina/farmacocinética , Digestão/fisiologia , Modelos Biológicos , Polissorbatos/química
13.
ACS Appl Mater Interfaces ; 11(35): 31661-31670, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31430116

RESUMO

Curcumin has antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. However, the clinical application of curcumin has been restricted by the poor water solubility and low bioavailability of this molecule. In this work, hydrophobic porous silicon (pSi) particles were prepared by electrochemical etching method and grafted with the different hydrophobic groups on their surfaces. The loading efficiency of curcumin in pSi has been investigated. The properties of pSi particles have been characterized by scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FTIR). The highest loading efficiency of curcumin can be obtained with pSi surface modified with the octadecyl silane group. The release properties of curcumin in hydrophobic pSi have been researched in vitro and in vivo. The curcumin in the hydrophobic pSi surface keeps a high antioxidant bioactivity. The toxicological evaluation of the hydrophobic pSi particles indicates they have a high in vivo biocompatibility within the observed dose ranges. The hydrophobic pSi particles could provide an effective and controlled release delivery carrier for curcumin, which may provide a new tool platform for the further development of curcumin.


Assuntos
Curcumina , Sistemas de Liberação de Medicamentos , Silício , Administração Oral , Animais , Disponibilidade Biológica , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Porosidade , Silício/química , Silício/farmacocinética , Silício/farmacologia
14.
Food Chem ; 299: 125097, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31284242

RESUMO

The low solubility, instability, and low bioavailability of food bioactive compounds such as polyphenols and flavonoids, restrict their applications in the fields of food science and nutrition. Ferritin protein has received more and more attention in encapsulation and delivery of the bioactive compounds due to its nanosized shell-like structure and its reversible self-assembly character. After encapsulation, bioactive compounds can be functionalized by the ferritin vehicle to achieve stabilization, solubilization, and targeted delivery. In addition, the outer interfaces and the porous structure of ferritin are also artfully harnessed for encapsulation. This review focuses on the newest advances in the fabrication, characterization, and application of ferritin-based nano-carriers for bioactive compounds by the reversible self-assembly, outer-interface decoration methods, and the channel-directed approach. The functional improvements of food bioactive compounds, including their solubility, stability, and cellular uptake, are emphasized. The limitations that affect ferritin encapsulation are also examined.


Assuntos
Ferritinas/química , Ferritinas/farmacocinética , Alimentos , Nanoestruturas/química , Antocianinas/administração & dosagem , Antocianinas/química , Antocianinas/farmacocinética , Disponibilidade Biológica , Catequina/análogos & derivados , Catequina/química , Quitosana/química , Curcumina/administração & dosagem , Curcumina/química , Curcumina/farmacocinética , Humanos , Polifenóis/administração & dosagem , Polifenóis/química , Polifenóis/farmacocinética , Proantocianidinas/administração & dosagem , Proantocianidinas/química , Proantocianidinas/farmacocinética , Solubilidade , beta Caroteno/administração & dosagem , beta Caroteno/química , beta Caroteno/farmacocinética
15.
Nutrients ; 11(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288419

RESUMO

Nanoparticle formulations improve bioavailability and so may allow low-dose formulations of food-derived compounds such as curcumin to attenuate chronic systemic disease despite intrinsically low oral bioavailability. The current study induced metabolic syndrome in male Wistar rats aged eight-nine weeks using a high-carbohydrate, high-fat diet (H) with corn starch diet (C) as control. Using a reversal protocol, rats were given curcumin as either nanoparticles encapsulated in poly(lactic-co-glycolic acid) (5 mg/kg/day, HCNP) or as an unformulated low dose or high-dose suspension in water (low-dose, 5 mg/kg/day, HC5; high-dose, 100 mg/kg/day, HC100) or blank nanoparticles (HBNP) for the final eight weeks of the 16 week study. We analysed cardiovascular parameters including systolic blood pressure and left ventricular diastolic stiffness along with histopathology, liver parameters including plasma liver enzymes, histopathology and metabolic parameters, including glucose tolerance, blood lipid profile and body composition, and plasma curcumin concentrations. HC100 and HCNP but not HBNP normalised systolic blood pressure (C = 120 ± 4; H = 143 ± 5; HBNP = 141 ± 3; HC5 = 143 ± 4; HC100 = 126 ± 4; HCNP = 128 ± 4 mmHg), left ventricular diastolic stiffness and liver fat deposition. No other improvements were induced in HC100 or HCNP or other intervention groups (HC5 and HBNP). We conclude that 5 mg/kg/day curcumin nanoparticles in H rats showed similar improvements in cardiovascular function as 100 mg/kg/day unformulated curcumin correlating with similar plasma curcumin concentrations.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Curcumina/farmacologia , Síndrome Metabólica , Nanopartículas/química , Animais , Disponibilidade Biológica , Curcumina/farmacocinética , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta , Gorduras na Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/fisiopatologia , Ratos , Ratos Wistar
16.
Food Chem ; 298: 125091, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31272049

RESUMO

The complexation of Lepidium sativum protein hydrolysate (LSPH) with a lipophilic molecule, curcumin (CUR), and its effect on curcumin in vitro bioaccessibility/stability, functional and antioxidant activity were investigated. Fluorescence spectroscopy of the LSPH/CUR complex confirmed the presence of hydrophobic interactions that led to the complex formation. The LSPH (10-30 kDa) fraction showed a compact complexation with curcumin at pH 3.0 with excellent aqueous solubility, stability, and bioaccessibility. Further, complexation enhanced the aqueous solubility of curcumin more than 856-fold. In vitro sequential simulated gastric and intestinal digestion indicated that the bioaccessibility of curcumin was increased from 67% to 95% post complexation. The functional attributes suggest that the LSPH/CUR complex has good foam-forming capacity and emulsion stability, which are crucial for food product formulations. The results indicate that, since LSPH is a dietary protein, it might possibly be formulated as a functional food and as an excellent lipophilic bioactive molecule delivery vehicle in food formulations.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Lepidium sativum/química , Hidrolisados de Proteína/química , Disponibilidade Biológica , Curcumina/farmacocinética , Digestão , Portadores de Fármacos/química , Emulsões/química , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Espectrometria de Fluorescência
17.
AAPS PharmSciTech ; 20(7): 254, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317354

RESUMO

The pathophysiological mechanisms for dry and wet age-related macular degeneration (AMD) involve oxidative stress and increased VEGF release and expression. An ideal drug candidate for both types of AMD is the one which offers significant protection to the retinal cells from oxidative stress and inhibit VEGF release. Curcumin is one such natural product which provides numerous beneficial effects including antioxidant, anti-inflammatory, and anti-VEGF activities and has the potential for the treatment of both types of AMD. The bioavailability of curcumin is negligible due to its poor aqueous solubility. The purpose of this work is to develop an aqueous nanomicellar drop formulation of curcumin (CUR-NMF) for back of the eye delivery utilizing hydrogenated castor oil (HCO-40) and octoxynol-40 (OC-40) to treat AMD. A full factorial design was performed with JMP software analysis to optimize the formulation size, polydispersity index (PDI), entrapment efficiency, loading, and precipitation. MTT and LDH assays on human retinal pigmented epithelial (D407) cells revealed that 5-10 µM CUR-NMF dose is safe for ophthalmic use. Furthermore, CUR-NMF exhibited significant protection of retinal (D407) cells against H2O2-induced oxidative stress. In vitro drug release kinetics suggested a sustained drug release profile indicating a long-term protection ability of CUR-NMF against oxidative stress to retinal cells. In addition, an ELISA suggested that CUR-NMF significantly reduces vascular endothelial growth factor (VEGF) release in D407 cell line, hence diminishes the risk of angiogenesis. Collectively, these results suggest that the proposed CUR-NMF can be tremendously effective in treating both types of AMD.


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Olho/metabolismo , Micelas , Nanoestruturas , Administração Oftálmica , Antioxidantes/química , Disponibilidade Biológica , Óleo de Rícino/química , Linhagem Celular , Curcumina/farmacologia , Preparações de Ação Retardada , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Int J Nanomedicine ; 14: 4683-4695, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308653

RESUMO

Purpose: Clinical applications of curcumin (Cur) have been greatly restricted due to its low solubility and poor systemic bioavailability. Three-arm amphiphilic copolymer tricarballylic acid-poly (ε-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) nanoparticles (NPs) were designed to improve the solubility and bioavailability of Cur. The present study adopted a microchannel system to precisely control the preparation of self-assembly polymeric NPs via liquid flow-focusing and gas displacing method. Methods: The amphiphilic three-arm copolymer Tri-CL-mPEG was synthesized and self-assembled into nearly spherical NPs, yielding Cur encapsulated into NP cores (Cur-NPs). The obtained NPs were evaluated for physicochemical properties, morphology, toxicity, cellular uptake by A549 cells, release in vitro, biodistribution, and pharmacokinetics in vivo. Results: Rapidly fabricated and isodispersed Cur-NPs prepared by this method had an average diameter of 116±3 nm and a polydispersity index of 0.197±0.008. The drug loading capacity and entrapment efficiency of Cur-NPs were 5.58±0.23% and 91.42±0.39%, respectively. In vitro release experiments showed sustained release of Cur, with cumulative release values of 40.1% and 66.1% at pH 7.4 and pH 5.0, respectively, after 10 days post-incubation. The results of cellular uptake, biodistribution, and in vivo pharmacokinetics experiments demonstrated that Cur-NPs exhibited better biocompatibility and bioavailability, while additionally enabling greater cellular uptake and prolonged circulation with possible spleen, lung, and kidney targeting effects when compared to the properties of free Cur. Conclusion: These results indicate that Tri-CL-mPEG NPs are promising in clinical applications as a controllable delivery system for hydrophobic drugs.


Assuntos
Curcumina/farmacologia , Microfluídica/métodos , Nanopartículas/química , Polietilenoglicóis/química , Polímeros/química , Ácidos Tricarboxílicos/química , Células A549 , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/farmacocinética , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Humanos , Camundongos , Peso Molecular , Nanopartículas/ultraestrutura , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Sprague-Dawley , Distribuição Tecidual/efeitos dos fármacos
19.
Pharm Dev Technol ; 24(9): 1164-1174, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31340709

RESUMO

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Curcumina/administração & dosagem , Docetaxel/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Octreotida/administração & dosagem , Células A549 , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Curcumina/análogos & derivados , Curcumina/farmacocinética , Curcumina/uso terapêutico , Docetaxel/farmacocinética , Docetaxel/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Octreotida/análogos & derivados , Octreotida/farmacocinética , Octreotida/uso terapêutico , Polietilenoglicóis/química , Polivinil/química
20.
AAPS PharmSciTech ; 20(6): 252, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300965

RESUMO

The objective of the present study was to investigate the effect of partially hydrolyzed ginsenoside on the physicochemical properties and in vitro release of curcumin from phospholipid-based nanostructured lipid carrier (NLC). NLC formulas modified with partially hydrolyzed ginsenoside (NLC-PG) were prepared with different amounts of ginsenoside using the conventional hot-melt method. The average particle size of curcumin-loaded NLC-PG ranged from 150 to 200 nm, and polydispersity index was in the range of 0.101-0.177, indicating monodispersed particle size distribution. Optical microscopy showed no sedimentation or recrystallization of curcumin even at 10,000 µg/ml concentration as NLC-PG in distilled water, indicating significantly enhanced solubility. TEM image showed that the nanoparticles were monodispersed with a multilayered core/shell structure. X-ray diffraction and FTIR spectroscopy showed that curcumin was amorphous in the NLC-PG, and there was no interaction between curcumin and the excipients. In vitro release study using simulated gastric/intestinal fluid media revealed that the release rate (Jss) of curcumin from the NLC-PG increased as a function of the ginsenoside content in the lipid carrier. Moreover, the Jss of curcumin kept gradually increasing in the presence of lipase, whereas in the presence of viscozyme, it sharply increased until the ginsenoside content reached 9.09% and subsequently plateaued. Partially hydrolyzed ginsenoside increased the Jss of curcumin from curcumin-loaded NLC-PG and therefore may be useful for improving the bioavailability of curcumin.


Assuntos
Curcumina/química , Portadores de Fármacos/química , Ginsenosídeos/química , Lipídeos/química , Nanoestruturas/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacocinética , Curcumina/farmacocinética , Portadores de Fármacos/farmacocinética , Excipientes/química , Excipientes/farmacocinética , Ginsenosídeos/farmacocinética , Hidrólise , Lipídeos/farmacocinética , Lisofosfatidilcolinas/química , Lisofosfatidilcolinas/farmacocinética , Tamanho da Partícula , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacocinética , Óleo de Soja/química , Óleo de Soja/farmacocinética , Difração de Raios X/métodos
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