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1.
J Photochem Photobiol B ; 204: 111769, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31954264

RESUMO

The goal of this study was to investigate the protective effects of nanostructured lipid carriers (NLCs) and vitamin E loaded NLCs (Vit E-NLCs) on preventing hair damages and discoloration against UV radiation and thermal treatment. The NLCs and Vit E-NLCs were prepared using a high-pressure homogenization technique. At optimal conditions, they showed spherical particles with a mean particle size of ~140 nm and a polydispersity index of < 0.3. Up to 90% (w/w) vitamin E acetate incorporation efficacy was achieved. The protective efficacy of the model cream containing blank-NLCs (NLCs cream) or Vit E-NLCs (Vit E-NLCs cream) was investigated. Upon exposure to UV-light and heat, the FE-SEM images revealed that the hair treated with both NLCs creams showed a smoothness of hair surface similar to the virgin hair. In accordance with protein loss, they exhibited the least protein loss as compared to the hair treated with Vit-E cream, cream base and commercial products. The same trend was observed for the discoloration test, the hair treated with both NLCs creams demonstrated the lowest total color loss, as compared to other products. Comparing between two NLCs formulations, antioxidant Vit E-NLCs showed to promote the photoprotective effect against hair damage and discoloration slightly greater than blank NLCs, but it has no extra benefit for heat protection. Considered overall, the developed NLCs and Vit E-NLCs is a novel alternative for preventing hair damage and discoloration from daily UV and heat exposure.


Assuntos
Portadores de Fármacos/química , Cabelo/efeitos dos fármacos , Lipídeos/química , Nanoestruturas/química , Raios Ultravioleta , Animais , Cor , Composição de Medicamentos , Cabelo/efeitos da radiação , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Temperatura Ambiente , Vitamina E/química , Vitamina E/farmacologia
2.
Chemistry ; 26(11): 2470-2477, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31912555

RESUMO

Multidrug resistance (MDR) is regarded as a main obstacle for effective chemotherapy, and P-glycoprotein (P-gp)-mediated drug efflux has been demonstrated to be the key factor responsible for MDR. In this study, a novel pH-responsive hybrid drug delivery system was developed by conjugating d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a kind of P-gp inhibitor, on the surface of laponite nanodisks to overcome MDR. The prepared LM-TPGS display excellent colloidal stability, a high encapsulation efficiency of doxorubicin (DOX), and a pH-responsive drug release profile. In vitro experiments verified that LM-TPGS/DOX could exhibit significantly enhanced therapeutic efficacy in treating DOX-resistant breast cancer cells (MCF-7/ADR) through inhibiting the activity of P-gp-mediated drug efflux and effectively accumulating DOX within cancer cells. In vivo results revealed that LM-TPGS/DOX outstandingly suppressed MCF-7/ADR tumors with low side effects. Therefore, the high drug payload, enhanced inhibition efficacy to drug-resistant cells, and low side effects make the LM-TPGS/DOX a promising nanoplatform to reverse MDR for effective chemotherapy.


Assuntos
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Nanocápsulas/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Composição de Medicamentos/métodos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Vitamina E/química , Vitamina E/metabolismo
3.
Int J Vitam Nutr Res ; 90(1-2): 5-16, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31724483

RESUMO

α-Tocopherol is the main compound of vitamin E with great antioxidant activity. However, like other functional lipid bioactive compounds, it suffers from low bioavailability due to its low water solubility and liable chemical structure. A bottom-up procedure based on a solvent-displacement method was constructed for fabrication of α-tocopherol nanodispersions using response surface methodology (RSM). The effects of main formulation parameters, namely, weight ratio of emulsifier to α-tocopherol and volumetric percent of acetone to water on the average particle size (nm), polydispersity index, concentration of α-tocopherol loss (% w/w) and turbidity of the nanodispersions were evaluated and optimized to gain the most desirable nanodispersions (least particle size, polydispersity index, turbidity and highest α-tocopherol concentrations). Second order regression equations, holding quite high coefficients of determination (R2 and adjusted R2 > 0.882), were significantly (p-value < 0.05) fitted for predicting the α-tocopherol nanodispersion characteristics variations as functions of studied formulation parameters. A multiple optimization analysis offered 6.5 and 10% for weight ratio of Tween 20 to α-tocopherol and volume percent of acetone, respectively, as overall optimum values for studied parameters. Statistically insignificant differences between experimental and predicted values of studied responses, verified the satisfactoriness of presented models for explaining the response characteristics as a function of formulation parameters. Thus, the employed solvent-displacement technique may provide the most desired water dispersible α-tocopherol nanoparticles for several water-based foods, cosmetic nutraceutical formulations.


Assuntos
Vitamina E , alfa-Tocoferol , Emulsões , Tamanho da Partícula , Solventes , Vitamina E/química , alfa-Tocoferol/química
4.
Food Chem ; 310: 125784, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31816534

RESUMO

Bioactive compounds demonstrating antioxidant activity were analyzed in berries and leaves of nine cultivars of sea buckthorn (Hippophaë rhamnoides L.) of various ripening times. Total polyphenols were ranging between 0.70-3.62 g GAE.kg-1 (berries) and 1.88-3.72 g GAE.kg-1 (leaves). Leaves were significantly richer source of total flavonoids (14.40-49.44 mg RE.kg-1) in comparison with berries (0.55-4.11 mg RE.kg-1). Phenolic compounds, carotenoids and vitamins were determined using high-performance liquid chromatography with a diode array detection. The content of vitamin C was 0.98-3.65 g.kg-1 in berries and 22.81-46.32 g.kg-1 in leaves, vitamin E content was 6.98-29.91 g.kg-1 in berries and 71.54-153.99 g.kg-1 in leaves. Distribution of individual phenolic compounds varied, their total content in berries was considerably lower (76.1-205.2 mg.kg-1) than in leaves (1477.7-8709.0 mg.kg-1). Regarding antioxidant activity, Raisa and Slovan (berries) and Bojan and Maslicnaja (leaves) were evaluated as the best cultivars.


Assuntos
Antioxidantes/análise , Ácido Ascórbico/análise , Frutas/química , Hippophae/química , Folhas de Planta/química , Vitamina E/análise , Antioxidantes/química , Ácido Ascórbico/química , Carotenoides/análise , Cromatografia Líquida de Alta Pressão , República Tcheca , Flavonoides/análise , Frutas/fisiologia , Hippophae/fisiologia , Fenóis/análise , Fenóis/química , Polifenóis/análise , Vitamina E/química
5.
Int J Vitam Nutr Res ; 90(1-2): 156-168, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31017555

RESUMO

Protective effects of vitamin E (Vit E) on long term potentiation (LTP) impairment, neuronal apoptosis and increase of nitric oxide (NO) metabolites in the hippocampus of juvenile rats were examined. The rats were grouped (n=13) as: (1) control; (2) hypothyroid (Hypo) and (3) Hypo-Vit E. Propylthiouracil (PTU) was given in drinking water (0.05%) during 6 weeks. Vit E (20 mg/ kg) was daily injected (IP). To evaluate synaptic plasticity, LTP from the CA1 area of the hippocampus followed by high frequency stimulation to the ipsilateral Schafer collateral pathway was carried out. The cortical and hippocampal tissues were then removed to measure NO metabolites. The brains of 5 animals in each group were removed for apoptosis study. The hypothyroidism status decreased the slope, 10-90% slope and amplitude of field excitatory post synaptic potential (fEPSP) compared to the control group (P<0.01-P<0.001). Injection of Vit E increased the slope, 10-90% slope and amplitude of the fEPSP in the Hypo-Vit E group in comparison to the Hypo group (P<0.05-P<0.01). TUNEL positive neurons and NO metabolites were higher in the hippocampus of the Hypo rats, as compared to those in the hippocampus of the control ones (P<0.001). Treatment of the Hypo rats by Vit E decreased apoptotic neurons (P<0.01-P<0.001) and NO metabolites (P<0.001) in the hippocampus compared to the Hypo rats. The results of the present study showed that Vit E prevented the LTP impairment and neuronal apoptosis in the hippocampus of juvenile hypothyroid rats.


Assuntos
Hipocampo/efeitos dos fármacos , Hipotireoidismo , Potenciação de Longa Duração , Vitamina E/farmacologia , Animais , Hipotireoidismo/tratamento farmacológico , Ratos , Ratos Wistar , Vitamina E/química
6.
Anal Bioanal Chem ; 412(3): 795-802, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31858167

RESUMO

Countercurrent chromatography (CCC) was used for the enrichment of α-tocodienol (α-T2), a rare vitamin E-related minor compound previously tentatively detected in palm oil. Hitherto, only one isomer has been mentioned to occur at traces in palm oil. However, CCC fractionation followed by GC/MS measurements of all fractions resulted in the detection of two α-T2 isomers in five different palm oil vitamin E dietary supplement capsules. Five repetitive CCC separations of ~ 1 g sample and additional purification steps by column chromatography provided ~ 2 mg of two equally abundant α-T2 isomers with a purity of ~ 85%. The positions of the double bonds in the alkyl side chain could be assigned by means of two characteristic chemical shifts in the 1H NMR spectrum. Accordingly, the structures of the α-T2 isomers were 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridec-3,11-dienyl)chroman-6-ol (double bonds in 3',11'-position) and 2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridec-7,11-dienyl)chroman-6-ol (double bonds in 7',11'-position). Natural occurrence of both isomers was proven by GC/MS screening of crude palm oil after saponification and CCC separation. Moreover, GC/MS analysis allowed the tentative assignment of γ-tocomonoenol (γ-T1) and ß-tocomonoenol (ß-T1) as trace compounds in palm oil.


Assuntos
Distribuição Contracorrente/métodos , Óleo de Palmeira/química , Vitamina E/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas , Isomerismo , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Vitamina E/química
7.
J Sci Food Agric ; 100(1): 129-138, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31452202

RESUMO

BACKGROUND: Capsaicin, as a major pungent ingredient of peppers, has many health benefits. However, the strong irritation effect of capsaicin inhibits its application in the food industry. Emulsions can be an effective approach to alleviate the irritation. RESULTS: In this study, we used tocopheryl polyethylene glycol 1000 succinate (TPGS) as an emulsifier to prepare capsaicin emulsions through high-pressure homogenization. Capsaicin emulsions with a particle size of about 100 nm, -36.4 mV zeta potential, and 91.9% encapsulation efficiency were prepared successfully and showed better environmental stability and higher antioxidant activity. Emulsions reduced the cumulative release of capsaicin and had no toxic effect on buffalo rat liver (BRL-3A) cells. Moreover, the gastrointestinal injury model of rats showed that emulsions reduced the strong irritation of capsaicin. CONCLUSION: This work provides a theoretical basis for the application of irritant ingredients in food industry. © 2019 Society of Chemical Industry.


Assuntos
Capsaicina/química , Capsaicina/metabolismo , Trato Gastrointestinal/metabolismo , Animais , Emulsificantes/química , Emulsões/química , Emulsões/metabolismo , Masculino , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Vitamina E/química
8.
Food Chem ; 306: 125582, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622834

RESUMO

When α-tocopherol (α-Toc) exerts its antioxidative effect, a portion of α-Toc is converted to certain oxidation products. Although accumulation of such oxidation products is considered to cause a deterioration in the quality of foods, their distribution and generation in food samples have been still unknown. In this study, we tried to analyze α-Toc hydroperoxide (Toc-OOH) stereoisomers and tocopherylquinone (TQ) in extra virgin olive oil (EVOO) using liquid chromatography-tandem mass spectrometry. Photo-irradiation (5000 lx) to EVOO increased Toc-OOH stereoisomers but not TQ. In contrast, thermal oxidation (150 °C) of EVOO increased TQ but not Toc-OOH. We considered that the generation of Toc-OOH and TQ were due to the [4+2]-cycloaddition reaction and proton donation from the phenolic hydrogen, respectively. Our data and method would be helpful for understanding of α-Toc oxidation mechanisms in edible oil samples or the estimation of food quality.


Assuntos
Azeite de Oliva/química , Vitamina E/análogos & derivados , alfa-Tocoferol/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Oxirredução , Espectrometria de Massas em Tandem , Vitamina E/análise , Vitamina E/química , alfa-Tocoferol/análise , alfa-Tocoferol/química
9.
J Agric Food Chem ; 67(43): 11931-11941, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31589419

RESUMO

Lipid-based delivery systems (LBDSs) are widely applied in pharmaceuticals and health care because of the increased bioavailability of lipophilic components when they are coadministered with high-fat meals. However, how to accurately control their in vivo release and stability is still challenging. Here, after introducing the simple esterification and coprecipitation, we created the dual-functional composite ODS-ß-CD-VE by the coassembly of ß-cyclodextrin (ß-CD), octadecenyl succinic anhydride (ODSA), and vitamin E (VE). The resulting dual-functional particle presented a uniform sheetlike shape and nanometer size. In addition, its chemical structure was clarified in detail via nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Benefiting from the antioxygenation of VE, lipid oxidation in the ODS-ß-CD-VE-stabilized Pickering emulsion was effectively inhibited. Meanwhile, pH-induced protonation/deprotonation of carboxyl groups guaranteed that the emulsions kept steady at pH ≤4 but were unsteady under neutral conditions. In this way, the lipids contained in the emulsion were protected from gastric juice and then digested and accurately released as n-3 polyunsaturated fatty acids (PUFA) in the simulated intestine environment. This strategy sheds some light on the rational and efficient construction of LBDSs for nutrient supplements and even pharmaceuticals in a living digestive tract.


Assuntos
Preparações de Ação Retardada/química , Ácidos Graxos Insaturados/química , Vitamina E/química , beta-Ciclodextrinas/química , Preparações de Ação Retardada/metabolismo , Digestão , Emulsões/química , Ácidos Graxos Insaturados/metabolismo , Trato Gastrointestinal/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Modelos Biológicos
10.
Pharm Nanotechnol ; 7(4): 304-313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31595848

RESUMO

BACKGROUND: Folic acid is essential in many metabolic processes and DNA synthesis. Nevertheless, folic acid is not stable, pH-sensitive, and deteriorated upon light exposure. OBJECTIVE: This work was aimed to improve folic acid stability within vitamin E-based nanoemulsion. METHODS: The nanoemulsion was prepared with self-nanoemulsification method by mixing vitamin E oil, Tween 20, and PEG 400. A pseudoternary phase diagram was constructed with aqueous titration to determine the optimum ratio for the mixture. The globule size, pH and entrapment efficiency were included in the nanoemulsion characterizations. In addition, the influence of centrifugation, storage, and pH on physical and chemical stabilities of folic acid nanoemulsion was evaluated. RESULTS: Optimum formula was obtained from vitamin E, Tween 20, and PEG 400 with the ratio of 1:11:1, and the folic acid amount was 8 mg. The size of folic acidloaded oil globule was 15.10 ± 1.51 nm, and the nanoemulsion pH was 6.24 ± 0.01. The nanoemulsion system was able to load the folic acid completely. Folic acid in nanoemulsion was stable after 14 days at room temperature, and it was more stable compared to folic acid in solution. In addition, the physical and chemical characteristics of folic acid in nanoemulsion was not affected by the simulated gastric condition. CONCLUSION: Hence, nanoemulsion is a promising strategy to enhance folic acid stability.


Assuntos
Emulsões/química , Ácido Fólico/química , Nanopartículas/química , Vitamina E/química , Administração Oral , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Emulsões/administração & dosagem , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Polietilenoglicóis/química , Polissorbatos/química , Vitamina E/administração & dosagem
11.
J Nutr Sci Vitaminol (Tokyo) ; 65(4): 285-302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474678

RESUMO

Recently a new assay method that can quantify the singlet oxygen absorption capacity (SOAC) of antioxidants (AOs) and food extracts was proposed. Singlet oxygen (1O2) quenching rates (kQ) and the relative SOAC values were measured for many carotenoids and phenolic AOs in ethanol/chloroform/D2O (50 : 50 : 1, v/v/v) solution at 35ºC using UV-vis spectrophotometry. It has been clarified that the SOAC method is useful to evaluate the 1O2-quenching activity of lipophilic and hydrophilic AOs having 5 orders of magnitude different rate constants (kQ). Measurements of the kQ and SOAC values were also performed for 39 kinds of food extracts. The results indicate that the SOAC method is useful to evaluate the 1O2-quenching activity of food extracts having two orders of magnitude different kQ values. Further, the kQ values for the reaction of 1O2 with 8 carotenoids and 8 vitamin E homologues were measured in an aqueous Triton X-100 (5.0 wt %) micellar solution (pH 7.4). Results obtained demonstrate that the kQ values of AOs in homogeneous and heterogeneous solutions vary notably depending on (i) polarity (dielectric constant (ε)) of the reaction field between AOs and 1O2, (ii) local concentration of AOs, and (iii) mobility of AOs in solution. Measurements of kQ and SOAC values in a micellar solution may be useful for evaluating the 1O2-quenching activity of AOs in biological systems. Furthermore, measurements of the SOAC values were performed for 32 kinds of food extracts using a microplate reader. The SOAC assay method was validated by inter-laboratory validation study due to 14 laboratories.


Assuntos
Antioxidantes/química , Análise de Alimentos/métodos , Alimentos , Oxigênio Singlete/química , Carotenoides/química , Fenômenos Químicos , Micelas , Fenóis/química , Reprodutibilidade dos Testes , Soluções/química , Espectrofotometria/métodos , Vitamina E/química
12.
Int J Pharm ; 570: 118609, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31415878

RESUMO

Previously, we synthesized 4-(N)-docosahexaenoyl 2', 2'-difluorodeoxycytidine (DHA-dFdC), a novel lipophilic compound with a potent, broad-spectrum antitumor activity. Herein, we report a solid lipid nanoparticle (SLN) formulation of DHA-dFdC with improved apparent aqueous solubility, chemical stability, as well as efficacy in a mouse model. The SLNs were prepared from lecithin/glycerol monostearate-in-water emulsions emulsified with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Tween 20. The resultant DHA-dFdC-SLNs were 102.2 ±â€¯7.3 nm in diameter and increased the apparent solubility of DHA-dFdC in water to at least 5.2 mg/mL, more than 200-fold higher than its intrinsic water solubility. DHA-dFdC in a lyophilized powder of DHA-dFdC-SLNs was significantly more stable than the waxy solid of pure DHA-dFdC. DHA-dFdC-SLNs also showed an increased cytotoxicity against certain tumor cells than DHA-dFdC. The plasma concentration of DHA-dFdC in mice intravenously injected with DHA-dFdC-SLNs in dispersion followed a bi-exponential model, with a half-life of ~44 h. In mice bearing B16-F10 murine melanoma, DHA-dFdC-SLNs were significantly more effective than DHA-dFdC in controlling the tumor growth. In addition, histology evaluation revealed a high level of apoptosis and tumor encapsulation in tumors in mice treated with DHA-dFdC-SLNs. DHA-dFdC-SLNs represents a new DHA-dFdC formulation with improved antitumor activity.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Desoxicitidina/química , Lipídeos/química , Nanopartículas/química , Solubilidade/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/síntese química , Emulsões/farmacologia , Feminino , Lecitinas/química , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Polietilenoglicóis/química , Vitamina E/química
13.
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
14.
Int J Nanomedicine ; 14: 5555-5567, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413562

RESUMO

Background: Vinpocetine (VPN) is a synthetic derivative of the Vinca minor alkaloids. The drug is characterized by a short half-life, limited water solubility and high hepatic first-pass effect. The objective was to develop different lipid-based nanocarriers (NCs) loaded into a thermosensitive in situ gelling (ISG) system to improve VPN bioavailability and brain targeting via intranasal (IN) delivery. Methods:  Different lipid-based NCs were developed and characterized for vesicle size, zeta potential, VPN entrapment efficiency (EE) and morphological characterization using transmission electron microscope (TEM). The prepared NCs were loaded into ISG formulations and characterized for their mucoadhesive properties. Ex-vivo permeation and histological study of the nasal mucosa were conducted. Pharmacokinetic and brain tissue distribution were investigated and compared to a marketed VPN product following administration of a single dose to rats. Results: VPN-D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) micelles nano-formulation showed the smallest particle size, highest EE among the studied NCs. TEM images revealed an almost spherical shape for all the prepared NCs. Among the NCs studied, VPN-loaded TPGS micelles demonstrated the highest percent cumulative VPN ex vivo permeation. All the prepared ISG formulations revealed the presence of mucoadhesive properties and showed no signs of inflammation or necrosis upon histological examination. Rats administered IN VPN-loaded TPGS-micelles ISG showed superior VPN concentration in the brain tissue and significant high relative bioavailability when compared to that received raw VPN-loaded ISG and marketed drug oral tablets. VPN-D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) micelles nano-formulation showed the smallest particle size, highest EE among the studied NCs. TEM images revealed an almost spherical shape for all the prepared NCs. Among the NCs studied, VPN-loaded TPGS micelles demonstrated the highest percent cumulative VPN ex vivo permeation. All the prepared ISG formulations revealed the presence of mucoadhesive properties and showed no signs of inflammation or necrosis upon histological examination. Rats administered IN VPN-loaded TPGS-micelles ISG showed superior VPN concentration in the brain tissue and significant high relative bioavailability when compared to that received raw VPN-loaded ISG and marketed drug oral tablets. Conclusion: VPN-loaded TPGS-micelles ISG formulation is a successful brain drug delivery system with enhanced bioavailability for drugs with poor bioavailability and those that are frequently administered.


Assuntos
Géis/administração & dosagem , Micelas , Temperatura Ambiente , Alcaloides de Vinca/administração & dosagem , Vitamina E/química , Administração Intranasal , Animais , Disponibilidade Biológica , Encéfalo/metabolismo , Bovinos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Lipídeos/química , Masculino , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley , Solubilidade , Distribuição Tecidual , Alcaloides de Vinca/sangue , Alcaloides de Vinca/farmacocinética
15.
Int J Nanomedicine ; 14: 5713-5728, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413571

RESUMO

Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that in normal cells, and rise rapidly under the influence of exogenous or endogenous inducing factors, eventually leading to the apoptosis of tumor cells. Therefore, this study prepared a dual pH/reducing-responsive poly (N-isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, PssNCT) nanogels, which employed two exogenous ROS inducers, cinnamaldehyde (CA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), to selectively induce apoptosis by regulating ROS levels in tumor cells. Methods: The PssNCT nanogels were prepared by the free radical precipitation polymerization under the crosslink between pH-sensitive hydrazone and reducing-sensitive disulfide bonds, followed by the physicochemical and morphological characteristics investigations. Plasma stability, dual pH/reducing responsive degradation and in vitro release were also assessed. In cell experiments, cytotoxicity in different cells were first detected. The intracellular ROS levels and mitochondrial functions of tumor cells were then evaluated. Moreover, the apoptosis and western-blot assays were employed to verify the association between ROS levels elevation and apoptosis in tumor cells. Results: The nanogels exhibited a round-like hollow structure with the diameter smaller than 200nm. The nanogels were stable in plasma, while showed rapid degradation in acidic and reducing environments, thus achieving significant release of CA and TPGS in these media. Furthermore, the sufficient amplification of ROS signals was induced by the synergistically function of CA and TPGS on mitochondria, which resulted in the opening of the mitochondrial apoptotic pathway and enhanced cytotoxicity on MCF-7 cells. However, nanogels barely affected L929 cells owing to their lower intracellular ROS basal levels. Conclusion: The specific ROS regulation method achieved by these nanogels could be explored to selectively kill tumor cells according to the difference of ROS signals in different kinds of cells.


Assuntos
Apoptose , Espaço Intracelular/química , Polietilenoglicóis/farmacologia , Polietilenoimina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acroleína/análogos & derivados , Acroleína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Vitamina E/síntese química , Vitamina E/química
16.
J Microencapsul ; 36(6): 552-565, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31403342

RESUMO

Taxane-based chemotherapy-loaded drug delivery systems have great potential for cancer treatment. The docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate)-b-d-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS) nanoparticles and the docetaxel (DTX)-loaded PAMAM-based poly (γ-benzyl-l-glutamate) (PAM-PBLG) nanoparticles were designed using a modified nanoprecipitation method. The particle size, encapsulation efficiency (EE), and in vitro release characteristics of the nanoparticles were tested. The effects of the two nanoparticles on the cellular uptake and cell viability on human cervical cancer cell line Hela and the human breast cancer cell line MCF-7 were compared. Furthermore, their antitumor efficiency was evaluated through in vivo tumour growth experiment in comparison with free DTX. PAM-PBLG-b-TPGS nanoparticles displayed high EE, smaller diameter, and a nice releasing profile. Besides, based on the high EE and 'self-controlled' drug release of the DTX-loaded PAM-PBLG-b-TPGS nanoparticles, they exhibited stronger cytotoxicity (lower survival rate) and higher uptake rate than DTX-loaded PAM-PBLG nanoparticles in Hela cells and MCF-7 cells. Furthermore, compared with DTX-loaded PAM-PBLG nanoparticles and free DTX, DTX-loaded PAM-PBLG-b-TPGS nanoparticles produced a potent anti-tumour effect. Thus, the DTX-loaded PAM-PBLG-b-TPGS nanoparticles provide a novel attractive nanocarrier for the DTX delivery of chemotherapy to human breast cancer cells and human cervical cancer cells.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Docetaxel/administração & dosagem , Portadores de Fármacos/química , Neoplasias do Colo do Útero/tratamento farmacológico , Vitamina E/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Dendrímeros/química , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias do Colo do Útero/patologia
17.
Curr Drug Deliv ; 16(7): 628-636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385769

RESUMO

BACKGROUND: The tocopherol-based excipient, TPM, when incorporated into a medium-chain triglyceride (MCT)-based lipid formulation, has been previously shown to improve the solubilization of Coenzyme Q10 (CoQ10) during in vitro digestion which is strongly correlated with enhanced exposure in vivo. METHODS: The current study aimed to gain further understanding of the MCT + TPM co-formulation, by assessing the formulation performance under fasted and fed in vitro digestion conditions, with different drug and excipient loading levels. Natural and synthetic-derived TPM were equivalent, and with d-α- tocopherol polyethylene glycol 1000 succinate (TPGS) outperformed other derivatives in enhancing the solubilisation of CoQ10 during digestion. RESULT: Fed conditions significantly improved the solubility of CoQ10 during in vitro digestion of the formulation in comparison with fasted conditions. The addition of TPM at 10% (w/w) of the total MCT + TPM provided optimal performance in terms of CoQ10 solubilization during digestion. CONCLUSION: The results further highlights the potential of TPM as an additive in lipid formulations to improve the solubilization and oral bioavailability of poorly water-soluble compounds.


Assuntos
Excipientes/química , Triglicerídeos/química , Ubiquinona/análogos & derivados , Vitamina E/química , Digestão , Jejum/metabolismo , Intestino Delgado/metabolismo , Fosforilação , Solubilidade , Ubiquinona/química
18.
Int J Biol Macromol ; 137: 878-885, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31284002

RESUMO

Crosslinked hydrogel composite membranes based on polyvinyl alcohol (PVA) and chitosan-loaded AgNO3 and vitamin E were prepared using gamma irradiation. Chitosan has been used as antimicrobial blend materials to provide further biocompatibility for the prepared composite hydrogel membranes. The crosslinking reaction between PVA and chitosan owing to gamma irradiation was verified and characterized by FTIR analysis, while the morphology of hydrogel composite membranes was investigated by SEM. Important parameters affecting on hydrogel membranes formation, such as copolymer concentration, irradiation dose, AgNO3 concentration, plasticizer, and vitamin E of PVA/chitosan membranes were evaluated and discussed in details. In addition, the mechanical and thermal properties of hydrogel composite membranes were examined to evaluate the possibility of its application for wound dressings. The results revealed that the gelation (%) of hydrogel membranes increased dramatically with PVA composition, irradiation dose and glycerol content up to 20%; however, it decreased with AgNP incorporation due to the viscosity of copolymer composition is hyper-increased. The swelling ratio of composed hydrogel membranes decreased notably with increasing the radiation dose and incorporation of AgNP, due to reducing of the crosslinking degree of formed hydrogel membranes. PVA-Cs-Ag composed hydrogel membranes showed significant antimicrobial activity in particular against Streptococcus mutans due to the presence of AgNP in membranes, compared to other bacteria and fungi microbes. Thus, the PVA/chitosan/AgNO3-Vit.E hydrogel composite membranes showed satisfactory properties for use as wound dressing materials.


Assuntos
Quitosana/química , Raios gama , Membranas Artificiais , Álcool de Polivinil/química , Nitrato de Prata/química , Vitamina E/química , Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Nanocompostos/química , Streptococcus mutans/efeitos dos fármacos , Temperatura Ambiente , Cicatrização/efeitos dos fármacos
19.
Int J Pharm ; 568: 118529, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31323368

RESUMO

Rapamycin as a novel macrolide immunosuppressive agent has been commonly used in organ transplantation owing to its stronger immunosuppressive effect, non-nephrotoxicity and lower side effect. However its drawbacks of low bioavailability and big individual difference remain to be improved in clinical application. Here rapamycin loaded TPGS-Lecithins-Zein nanoparticles (RTLZ-NPs) with core-shell structure were prepared by the phase separation method. The RTLZ-NPs were approximately 190.3 nm in size, with PDI and zeta potential about 0.256 and -19.71 mV respectively. Drug entrapment and loading achieved were about 86.64 and 25.73% respectively. Meanwhile RTLZ-NPs exhibited favorable enzymolysis resistance abilities in gastrointestinal environments and enhanced uptake in Caco-2 cells. The optimum absorption sites of rapamycin in the intestine were duodenum and jejunum as single-pass intestinal perfusion assay. Upon also considering the results of Caco-2 cell assay, it could be speculated that the transport of rapamycin in vivo involved active transport as well as P-glycoprotein (P-gp) based efflux. Finally, the relative oral bioavailability of RTLZ-NPS was 4.33 fold higher than free rapamycin in SD rat. Altogether the designed nanoparticles can be an efficient oral delivery strategy for rapamycin analogues to prevent the attacks from destructive enzymes, reduce cell efflux, increase cell uptake, and then enhance the oral bioavailability.


Assuntos
Portadores de Fármacos/administração & dosagem , Lecitinas/administração & dosagem , Nanopartículas/administração & dosagem , Sirolimo/administração & dosagem , Vitamina E/administração & dosagem , Zeína/administração & dosagem , Administração Oral , Animais , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/administração & dosagem , Cumarínicos/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Humanos , Absorção Intestinal/efeitos dos fármacos , Lecitinas/química , Lecitinas/farmacocinética , Masculino , Nanopartículas/química , Ratos Sprague-Dawley , Sirolimo/química , Sirolimo/farmacocinética , Tiazóis/administração & dosagem , Tiazóis/química , Vitamina E/química , Vitamina E/farmacocinética , Zeína/química , Zeína/farmacocinética
20.
Pharm Dev Technol ; 24(9): 1125-1132, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31305197

RESUMO

Clinically, co-delivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. This study was aimed at integrating the merits of combination chemotherapy and mixed micellar technology and demonstrating the anticancer potential of doxorubicin (DOX) and dihydroartemisinin (DHA) co-loaded Soluplus®-TPGS mixed micellar system. In this study, physiochemically stable multidrug loaded mixed micelles were successfully prepared, encapsulation efficiencies of DOX and DHA were as high as 90%, and the average diameter of the micelles was 64.27 nm. The cellular uptake of DOX from the mixed micelles increased by 1.3 and 1.2 times for MCF-7 and MCF-7/ADR cell lines, respectively. The micelles were more cytotoxic than free DHA-DOX. Surprisingly, the co-loaded mixed micelles exhibited higher antitumor activity, while the systemic toxicity was reduced during the treatment. Therefore, the DOX and DHA mixed micelle might be a potential, effective, and less toxic drug-delivery system for cancer therapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Doxorrubicina/administração & dosagem , Polietilenoglicóis/química , Polivinil/química , Vitamina E/química , Antibióticos Antineoplásicos/farmacologia , Antimaláricos/farmacologia , Artemisininas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Combinação de Medicamentos , Feminino , Humanos , Células MCF-7 , Micelas
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