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1.
Int J Nanomedicine ; 15: 4739-4752, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753862

RESUMO

Purpose: Combined chemotherapeutic drug and protein drug has been a widely employed strategy for tumor treatment. To realize both tumor accumulation and deep tumor penetration for drugs with different pharmacokinetics, we propose a structure-transformable, thermo-pH dual responsive co-delivery system to co-load granzyme B/docetaxel (GrB/DTX). Methods: Thermo-sensitive hydrogels based on diblock copolymers (mPEG-b-PELG) were synthesized through ring opening polymerization. GrB/DTX mini micelles (GDM) was developed by co-loading these two drugs in pH-sensitive mini micelles, and the GDM-incorporated thermo-sensitive hydrogel (GDMH) was constructed. The thermo-induced gelation behavior of diblock copolymers and the physiochemical properties of GDMH were characterized. GDMH degradation and deep tumor penetration of released mini micelles were confirmed. The pH-sensitive disassembly and lysosomal escape abilities of released mini micelles were evaluated. In vitro cytotoxicity was studied using MTT assays and the in vivo antitumor efficacy study was evaluated in B16-bearing C57BL/6 mice. Results: GDMH was gelatinized at body temperature and can be degraded by proteinase to release mini micelles. The mini micelles incorporated in GDMH can achieve deep tumor penetration and escape from lysosomes to release GrB and DTX. MTT results showed that maximum synergistic antitumor efficacy of GrB and DTX was observed at mass ratio of 1:100. Our in vivo antitumor efficacy study showed that GDMH inhibited tumor growth in the subcutaneous tumor model and in the post-surgical recurrence model. Conclusion: The smart-designed transformable GDMH can facilitate tumor accumulation, deep tumor penetration, and rapid drug release to achieve synergistic chemo-protein therapy.


Assuntos
Antineoplásicos/uso terapêutico , Hidrogéis/química , Neoplasias/tratamento farmacológico , Temperatura , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Docetaxel/uso terapêutico , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Feminino , Granzimas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Injeções , Camundongos Endogâmicos C57BL , Micelas , Neoplasias/patologia , Polietilenoglicóis/química
2.
Crit Rev Ther Drug Carrier Syst ; 37(3): 205-227, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749138

RESUMO

In this review, we describe the advances in oral drug delivery approaches for taxanes for successful therapeutic outcome. Taxanes (paclitaxel and docetaxel) have unwanted pharmacokinetic profiles when they are given in their current dosage forms. Taxanes have low bioavailability, are extensively metabolized by CYP3A, and have a high affinity for P-glycoprotein. Regardless of dosage schedule, the overall docetaxel or paclitaxel dose that a patient can tolerate at a given interval remains similar. Currently, there are no commercially available oral taxane nanoformulations, and there are still several challenges to overcome. Nano-based formulations may offer the best solutions to problems involving the safety and effectiveness of taxane delivery. Thus, further research is necessary before such taxane nanoformulations can be manufactured for clinical use.


Assuntos
Docetaxel/administração & dosagem , Paclitaxel/administração & dosagem , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Ensaios Clínicos como Assunto , Docetaxel/química , Docetaxel/farmacocinética , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Humanos , Lipídeos/administração & dosagem , Lipídeos/química , Micelas , Nanopartículas/administração & dosagem , Nanopartículas/química , Paclitaxel/química , Paclitaxel/farmacocinética
3.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(3): 364-374, 2020 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-32762172

RESUMO

OBJECTIVE: To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the in vitro anti-tumor activity of the drug-loaded micelles. METHODS: CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles in vitro were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells. RESULTS: FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. In vitro drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 µg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours. CONCLUSIONS: FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.


Assuntos
Nanoestruturas , Antineoplásicos , Quitosana , Doxorrubicina , Portadores de Fármacos , Ácido Fólico , Humanos , Micelas , Polímeros
4.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3136-3143, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726022

RESUMO

This study aimed to prepare evodiamine-glycyrrhizic acid(EVO-GL) micelles to enhance the anti-hepatic fibrosis activity of evodiamine. Firstly, EVO-GL micelles were prepared with use of thin film dispersion method. With particle size, encapsulation efficiency, loading capacity of micelles and the solubility of evodiamine as the indexes, the effect of different factors on micelles was observed to screen the optimal preparation methods and process. Then the pharmaceutical properties and the therapeutic effects of EVO-GL micelles prepared by optimal process were evaluated on CCl_4-induced hepatic fibrosis. The results showed that the micelles prepared by the thin film dispersion method had an even size, with an average particle size of(130.80±12.40)nm, Zeta potential of(-41.61±3.12) mV, encapsulation efficiency of 91.23%±1.22%, drug loading of 8.42%±0.71%, high storage stability at 4 ℃ in 3 months, and slow in vitro release. Experimental results in the treatment of CCl_4-induced hepatic fibrosis in rats showed that EVO-GL micelles had a synergistic anti-hepatic fibrosis effect, which significantly reduced the liver function index of hepatic fibrosis rats. In conclusion, the EVO-GL micelles prepared with glycyrrhizic acid as a carrier would have a potential application prospect for the treatment of hepatic fibrosis.


Assuntos
Ácido Glicirrízico , Micelas , Animais , Portadores de Fármacos , Cirrose Hepática , Tamanho da Partícula , Quinazolinas , Ratos , Solubilidade
5.
Food Chem ; 332: 127366, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619940

RESUMO

High methyl-esterified citrus pectin (HMCP) molecules could be self-assembled into micelles in water. The morphology of HMCP micelles in water was irregular spheres, long rods, and arc-shaped. Most of HMCP molecules cross-linked with HMCP micelles in the presence of calcium chloride and increased the range of size distribution of HMCP micelles. A little number of HMCP molecules cross-linked with each other to form 80 nn ~ 200 nm microgel particles. Calcium chloride could improve HMCP emulsification when its concentration was more than 70 mmol/L. HMCP micelles could be adsorbed on the surface of emulsion droplets. The emulsion prepared with HMCP and calcium chloride was similar to the Pickering emulsion.


Assuntos
Cloreto de Cálcio/química , Pectinas/química , Emulsões , Esterificação , Metilação , Micelas , Água/química
6.
Food Chem ; 330: 127209, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32535314

RESUMO

Bovine ß-casein is an amphiphilic protein that exists as a monomer and self-organizes into micelles in aqueous solution. The protein has been used as natural vehicles for bioactives. Trans-resveratrol has received significant attention due to its vast health benefits and conversion to cis-isomer during processing and storage. However, cis-isomer has not yet gained as much attention as that of trans-isomer. In this study, the interaction of ß-casein with trans- and cis-resveratrol was characterized. Trans-resveratrol exhibited a higher affinity for ß-casein than cis-isomer, and ß-casein could bind two isomers simultaneously to form protein-diligand complexes. Both trans- and cis-isomers could be encapsulated into ß-casein micelles with encapsulation efficiencies of ~69% and ~57%, respectively. The ß-casein micelles could delay photo-isomerization of trans-isomer to cis-isomer, while ß-casein-ligand complex showed a better protective effect for both isomers during storage than ß-casein micelles. These results might be useful for the development of protein-based carriers for the polyphenols.


Assuntos
Caseínas/química , Excipientes/química , Resveratrol/química , Animais , Bovinos , Isomerismo , Ligantes , Micelas
7.
Int J Nanomedicine ; 15: 3539-3550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547012

RESUMO

Background: Methotrexate (MTX) is an antiproliferative drug widely used to treat inflammatory diseases and autoimmune diseases. The application of percutaneous administration is hindered due to its poor transdermal penetration. To reduce side effects and enhanced percutaneous delivery of MTX, novel methotrexate (MTX)-loaded micelles prepared with a amphiphilic cationic material, N,N-dimethyl-(N',N'-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSAP), was designed. Materials and Methods: DMSAP was synthesized via three steps using simple chemical agents. H nuclear magnetic resonance and mass spectroscopy were used to confirm the successful synthesis of DMSAP. A safe and non-toxic phosphatidylcholine, soybean phosphatidylcholine (SPC), was added to DMSAP at different ratios to form P/D-micelles. Then, MTX-entrapped micelles (M/P/D-micelles) were prepared by electrostatic adsorption. The physicochemical properties and blood stability of micelles were examined thoroughly. In addition, the transdermal potential of the micelles was evaluated by permeation experiments. Results: In aqueous environments, DMSAP conjugates could self-assemble spontaneously into micelles with a low critical micelle concentration (CMC) of 0.056 mg/mL. Stable, spherical MTX-entrapped micelles (M/P/D-micelles) with a size of 100-120 nm and high zeta potential of +36.26 mV were prepared. In vitro permeation studies showed that M/P/D-micelles exhibited superior skin permeability and deposition of MTX in the epidermis and dermis compared with that of free MTX. Conclusion: These special novel cationic M/P/D-micelles can enhance the permeability of MTX and are expected to be a promising percutaneous delivery system for therapy skin diseases.


Assuntos
Metotrexato/administração & dosagem , Micelas , Administração Cutânea , Animais , Cátions , Bovinos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Metotrexato/química , Camundongos , Concentração Osmolar , Tamanho da Partícula , Fosfatidilcolinas/química , Espectroscopia de Prótons por Ressonância Magnética , Soroalbumina Bovina/química , Pele/efeitos dos fármacos , Eletricidade Estática
8.
Int J Nanomedicine ; 15: 3563-3576, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547014

RESUMO

Background: LA67 is a derivative of triptolide that exhibits strong antitumor activity. This derivative has a better safety profile than triptolide, but is limited by poor aqueous solubility. Aim and Methods: To improve solubility and further increase therapeutic efficacy, we prepared LA67-loaded polymeric micelles (LA67-PMs) using a film hydration method. The physicochemical properties of LA67-PMs were investigated, and the antitumor activity of this formulation against Colon26 (C26) cancer cell line was evaluated in vitro and in vivo with LA67 as a control. Results: Polymeric micelles containing LA67 had a particle size of 17.88 nm and a drug entrapment efficiency of 94.84%. This formulation dispersed completely in aqueous solution and exhibited slow, sustained release of LA67. Cellular uptake assay showed that LA67-PMs delivered LA67 to cancer cells with greater efficiency than free LA67, which resulted in increased LA67 accumulation in cancer cells. Cell counting kit 8 (CCK-8) assay showed that blank polymeric micelles (PMs) exhibited low toxicity and LA67-PMs exerted pronounced anti-proliferation effects against C26 cells. Furthermore, LA67-PMs induced apoptosis and repressed migration more effectively than free LA67. In vivo evaluation of antitumor activity showed that LA67-PMs inhibited tumor growth and distant organ metastasis to a greater extent than LA67, which resulted in improved survival rate. The potential mechanisms of these effects may have been induction of apoptosis, inhibition of cell proliferation, and neovascularization. Conclusion: Our study showed that LA67-PMs may be a promising formulation for treatment of colon cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Micelas , Nanopartículas/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/irrigação sanguínea , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Metástase Neoplásica , Neovascularização Patológica/tratamento farmacológico , Tamanho da Partícula , Solubilidade , Análise de Sobrevida
9.
Int J Nanomedicine ; 15: 3319-3331, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32494132

RESUMO

Background: It is of great significance to develop intelligent co-delivery systems for cancer chemotherapy with improved therapeutic efficacy and few side-effects. Materials and Methods: Here, we reported a co-delivery system based on pH-sensitive polyprodrug micelles for simultaneous delivery of doxorubicin (DOX) and paclitaxel (PTX) as a combination chemotherapy with pH-triggered drug release profiles. The physicochemical properties, drug release profiles and mechanism, and cytotoxicity of PTX/DOX-PMs have been thoroughly investigated. Results and Discussion: The pH-sensitive polyprodrug was used as nanocarrier, and PTX was encapsulated into the micelles with high drug-loading content (25.6%). The critical micelle concentration (CMC) was about 3.16 mg/L, indicating the system could form the micelles at low concentration. The particle size of PTX/DOX-PMs was 110.5 nm, and increased to approximately 140 nm after incubation for 5 days which showed that the PTX/DOX-PMs had high serum stability. With decrease in pH value, the particle size first increased, and thenwas no longer detectable. Similar change trend was observed for CMC values. The zetapotential increased sharply with decrease in pH. These results demonstrated the pHsensitivity of PTX/DOX-PMs. In vitro drug release experiments and study on release mechanism showed that the drug release rate and accumulative release for PTX and DOX were dependent on the pH, showing the pH-triggered drug release profiles. Cytotoxicity assay displayed that the block copolymer showed negligible cytotoxicity, while the PTX/DOX-PMs possessed high cytotoxic effect against several tumor cell lines compared with free drugs and control. Conclusion: All the results demonstrated that the co-delivery system based on pH-sensitive polyprodrug could be a potent nanomedicine for combination cancer chemotherapy. In addition, construction based on polyprodrug and chemical drug could be a useful method to prepare multifunctional nanomedicine.


Assuntos
Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Micelas , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico , Pró-Fármacos/farmacologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Células NIH 3T3 , Neoplasias/patologia , Paclitaxel/farmacologia , Tamanho da Partícula , Polímeros/química , Eletricidade Estática
10.
J Chromatogr A ; 1623: 461146, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505269

RESUMO

In micellar liquid chromatography (MLC), the addition of a surfactant to the mobile phase in excess is accompanied by an alteration of its solubilising capacity and a change in the stationary phase's properties. As an implication, the prediction of the analytes' retention in MLC mode becomes a challenging task. Mixed Quantitative Structure - Retention Relationships (QSRR) modelling represents a powerful tool for estimating the analytes' retention. This study compares 48 successfully developed mixed QSRR models with respect to their ability to predict retention of aripiprazole and its five impurities from molecular structures and factors that describe the Brij - acetonitrile system. The development of the models was based on an automatic combining of six attribute (feature) selection methods with eight predictive algorithms and the optimization of hyper-parameters. The feature selection methods included Principal Component Analysis (PCA), Non-negative Matrix Factorization (NMF), ReliefF, Multiple Linear Regression (MLR), Mutual Info and F-Regression. The series of investigated predictive algorithms comprised Linear Regressions (LR), Ridge Regression, Lasso Regression, Artificial Neural Networks (ANN), Support Vector Regression (SVR), Random Forest (RF), Gradient Boosted Trees (GBT) and K-Nearest neighbourhood (k-NN). A sufficient amount of data for building the model (78 cases in total) was provided by conducting 13 experiments for each of the 6 analytes and collecting the target responses afterwards. Different experimental settings were established by varying the values of the concentration of Brij L23, pH of the aqueous phase and acetonitrile content in the mobile phase according to the Box-Behnken design. In addition to the chromatographic parameters, the pool of independent variables was expanded by 27 molecular descriptors from all major groups (physicochemical, quantum chemical, topological and spatial structural descriptors). The best model was chosen by taking into consideration the Root Mean Square Error (RMSE) and cross-validation (CV) correlation coefficient (Q2) values. Interestingly, the comparative analysis indicated that a change in the set of input variables had a minor impact on the performance of the final models. On the other hand, different regression algorithms showed great diversity in the ability to learn patterns conserved in the data. In this regard, testing many regression algorithms is necessary in order to find the most suitable technique for model building. In the specific case, GBT-based models have demonstrated the best ability to predict the retention factor in the MLC mode. Steric factors and dipole-dipole interactions have proven to be relevant to the observed retention behaviour. This study, although being of a smaller scale, is a most promising starting point for comprehensive MLC retention prediction.


Assuntos
Algoritmos , Cromatografia Líquida/métodos , Micelas , Relação Quantitativa Estrutura-Atividade , Antipsicóticos/química , Automação , Bases de Dados como Assunto , Modelos Lineares , Reprodutibilidade dos Testes , Solventes/química
11.
Nat Commun ; 11(1): 2793, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493905

RESUMO

Biology utilizes multiple strategies, including sequestration in lipid vesicles, to raise the rate and specificity of chemical reactions through increases in effective molarity of reactants. We show that micelle-assisted reaction can facilitate native chemical ligations (NCLs) between a peptide-thioester - in which the thioester leaving group contains a lipid-like alkyl chain - and a Cys-peptide modified by a lipid-like moiety. Hydrophobic lipid modification of each peptide segment promotes the formation of mixed micelles, bringing the reacting peptides into close proximity and increasing the reaction rate. The approach enables the rapid synthesis of polypeptides using low concentrations of reactants without the need for thiol catalysts. After NCL, the lipid moiety is removed to yield an unmodified ligation product. This micelle-based methodology facilitates the generation of natural peptides, like Magainin 2, and the derivatization of the protein Ubiquitin. Formation of mixed micelles from lipid-modified reactants shows promise for accelerating chemical reactions in a traceless manner.


Assuntos
Lipídeos/química , Micelas , Peptídeos/química , Tensoativos/química , Sequência de Aminoácidos , Cinética , Luz , Magaininas/síntese química , Magaininas/química , Peptídeos/síntese química , Ubiquitina/metabolismo
12.
J Chromatogr A ; 1623: 461212, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505296

RESUMO

Non-ionic surfactants such as polysorbates, known as Tween™ 20 and Tween™ 80, are routinely used within the healthcare and pharmaceutical industry to enhance solubility. This work focuses on analysing the two aforementioned polysorbates, each considered at three purity levels with four model compounds, across the critical micellar concentration (CMC) range for each surfactant. Such data is of interest to investigate the influence of micelle formation upon compound-polysorbate interaction. Two analytical techniques were utilised, namely spectroscopic solubility determination and micellar liquid chromatography (MLC). In all cases it was apparent that the maximum solubility for all four compounds increased substantially at concentrations greater than the CMC and that, in most cases, a different retention profile was observed using MLC once the CMC had been exceeded. This paper is the first to have used such techniques to investigate the behaviour of these polysorbates over a series of concentrations and three levels of polysorbate purity. The findings indicate that the solubilisation potential of polysorbates differs once the CMC has been surpassed and is dependent upon the level of purity selected, i.e. compound-surfactant interactions are partially a consequence of the presence of micelles rather than monomer as well as polysorbate purity. Thus, formulators should include such polysorbates at optimised concentrations and purity if they wish to maximise their solubilisation potential.


Assuntos
Micelas , Polissorbatos/química , Acetaminofen/análise , Benzamidas/análise , Cromatografia Líquida , Hidrocortisona/análise , Solubilidade , Tensoativos/química
13.
Life Sci ; 255: 117858, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497635

RESUMO

At present, cervical cancer is the fourth leading cause of cancer among women worldwide with no effective treatment options. In this study we aimed to evaluate the efficacy of hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) photodynamic therapy (PDT) in a comprehensive panel of human cervical cancer-derived cell lines, including HeLa (HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and 18-positive), and C33A (HPV-negative), compared to a nontumorigenic human epithelial cell line (HaCaT). Were investigated: (i) cell cytotoxicity and phototoxicity, cellular uptake and subcellular distribution; (ii) cell death pathway and cellular oxidative stress; (iii) migration and invasion. Our results showed that HYP/P123 micelles had effective and selective time- and dose-dependent phototoxic effects on cervical cancer cells but not in HaCaT. Moreover, HYP/P123 micelles accumulated in endoplasmic reticulum, mitochondria and lysosomes, resulting in photodynamic cell death mainly by necrosis. HYP/P123 induced cellular oxidative stress mainly via type II mechanism of PDT and inhibited cancer cell migration and invasion mainly via MMP-2 inhibition. Taken together, our results indicate a potentially useful role of HYP/P123 micelles as a platform for HYP delivery to more specifically and effectively treat cervical cancers through PDT, suggesting they are worthy for in vivo preclinical evaluations.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas , Perileno/análogos & derivados , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Feminino , Células HeLa , Humanos , Micelas , Invasividade Neoplásica , Estresse Oxidativo/efeitos dos fármacos , Perileno/administração & dosagem , Perileno/farmacologia , Poloxaleno/química , Fatores de Tempo , Neoplasias do Colo do Útero/patologia
14.
Food Chem ; 327: 126970, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32473414

RESUMO

The self-assembly of Tween 80 (T80) micelles loaded with plant-based oregano essential oil (OR) and trans-cinnamaldehyde (TCA) was studied. The effect of different factors, including the surfactant to oil ratio, the presence of sodium chloride, thermal treatment, and dilution on their formation and physicochemical stability was evaluated. The creation of nano-cargos was confirmed by TEM. The self-associated structures had z-average droplet diameters of 92 to 337 nm without any energy input. Whereas addition of 10% (w/v) NaCl prevented the formation of oregano essential oil nano-assemblies of T80, swollen micelles containing TCA were successfully produced. Moreover, the OR or TCA loaded-micelles had only a slight droplet size variation upon thermal treatment. Ultimately, their antibacterial activity analysis against some food pathogens revealed that the encapsulation of OR and TCA within micelles crucially improved their antibacterial activity. These straightforward and cost-effective designed systems can be applicable in different products, including foods and agrochemicals.


Assuntos
Acroleína/análogos & derivados , Origanum/química , Compostos Fitoquímicos/química , Polissorbatos/química , Acroleína/química , Acroleína/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Emulsões/química , Micelas , Compostos Fitoquímicos/farmacologia , Salmonella/efeitos dos fármacos
15.
Chemosphere ; 256: 127044, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32428741

RESUMO

Various surfactants, such as nonionic Triton X-100 and Simple Green™ (SG), and anionic sodium dodecylsulfate (SDS) and sodium dodecylbenzene sulfonate (SDBS) were utilized to remove polycyclic aromatic hydrocarbons (PAHs) from heavily contaminated harbor sediments dredged from Kaohsiung Harbor in Taiwan. Desorption/re-sorption equilibrium, kinetics, and washability of PAHs using the selected surfactant were evaluated under different critical micelle concentrations (CMC). Experimental results revealed that the desorption rate of high molecular weight PAHs was greater than those of low molecular weight PAHs, and the anionic SDS was relatively effective in the removal of total PAHs (>50%) compared to the other surfactants. The correlation between the effectiveness of the surfactant washing processes and the physicochemical properties of individual PAH was statistically analyzed. The resulting data suggested that hydrophobic factors (Kow, Koc and Sw) affected PAH treatability more than the reactivity of PAH (electron affinity and ionization potential). Since the adsorption of anionic surfactant altered the hydrophobicity of organic matter in the sediment, PAHs preferred transferring from the sediment to the hydrophobic core of micelles in aqueous solution. Nevertheless, the nonionic surfactant enhanced the PAH partition in the aqueous phase, thus increasing the micellar solubilization of PAH.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Adsorção , Ânions , Micelas , Octoxinol/química , Dodecilsulfato de Sódio , Solubilidade , Tensoativos/química , Taiwan , Água/química
16.
Int J Nanomedicine ; 15: 2717-2732, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368051

RESUMO

Background: Phototherapy is a potential new candidate for glioblastoma (GBM) treatment. However inadequate phototherapy due to stability of the photosensitizer and low target specificity induces the proliferation of neovascular endothelial cells for angiogenesis and causes poor prognosis. Methods: In this study, we constructed c(RGDfk)-modified glycolipid-like micelles (cRGD-CSOSA) encapsulating indocyanine green (ICG) for dual-targeting neovascular endothelial cells and tumor cells, and cRGD-CSOSA/ICG mediated dual effect of PDT/PTT with NIR irradiation. Results: In vitro, cRGD-CSOSA/ICG inhibited cell proliferation and blocked angiogenesis with NIR irradiation. In vivo, cRGD-CSOSA/ICG exhibited increased accumulation in neovascular endothelial cells and tumor cells. Compared with that of CSOSA, the accumulation of cRGD-CSOSA in tumor tissue was further improved after dual-targeted phototherapy pretreatment. With NIR irradiation, the tumor-inhibition rate of cRGD-CSOSA/ICG was 80.00%, significantly higher than that of ICG (9.08%) and CSOSA/ICG (42.42%). Histological evaluation showed that the tumor vessels were reduced and that the apoptosis of tumor cells increased in the cRGD-CSOSA/ICG group with NIR irradiation. Conclusion: The cRGD-CSOSA/ICG nanoparticle-mediated dual-targeting phototherapy could enhance drug delivery to neovascular endothelial cells and tumor cells for anti-angiogenesis and improve the phototherapy effect of glioblastoma, providing a new strategy for glioblastoma treatment.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glioblastoma/terapia , Verde de Indocianina/administração & dosagem , Nanopartículas/administração & dosagem , Neovascularização Patológica/tratamento farmacológico , Fototerapia/métodos , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Glioblastoma/patologia , Glicolipídeos/química , Humanos , Verde de Indocianina/química , Camundongos Nus , Micelas , Nanopartículas/química , Oligopeptídeos/química , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Nanomedicine ; 15: 2885-2902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425522

RESUMO

Purpose: Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential. Methods: The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles. Results: The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity. Conclusion: Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Micelas , Paclitaxel/administração & dosagem , Polímeros/química , Animais , Antineoplásicos Fitogênicos/farmacocinética , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Ácido Fólico/química , Glutationa/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Células MCF-7 , Camundongos , Terapia de Alvo Molecular , Células NIH 3T3 , Oxirredução , Paclitaxel/farmacocinética , Coelhos , Ensaios Antitumorais Modelo de Xenoenxerto , alfa-Tocoferol/química
18.
Food Chem ; 327: 127088, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32454282

RESUMO

Evaluation of oxidizing lipid systems in terms of the kinetics governing both initiation and propagation phases will provide more comprehensive and reliable information than those based on the single-parameter analyses used frequently. The aim of this study was to promote the ordinarily used evaluation methods by using many kinetic parameters and rate constants representing the two phases. To do this, a variety of triacylglycerols of various fatty acid compositions were peroxidized over time at 60 °C and the kinetic curves of lipid hydroperoxides (LOOH) accumulation were drawn. The unifying parameters representative for the initiation (Oi = 0.23-181.41 mM-1 h2) and propagation (Rn = 0.0732-0.2847 h-1) oxidizabilities were interestingly able to differentiate the oils of even relatively similar compositions. Despite the more remarkable impact of saturation on Oi, polyunsaturation indicated a higher contribution to Rn. The critical concentration of LOOH reverse micelles showed significantly different values (10.0-41.6 mM) as a function of the saturation (9.7-29.8%), monounsaturation (22.5-70.4%), and polyunsaturation (11.0-64.3%) degrees. Such a terminology will provide researchers with lots of valuable kinetic information regarding oxidizability as a function of any intrinsic and/or extrinsic factor.


Assuntos
Lipídeos/química , Ácidos Graxos/química , Óleos de Peixe/química , Cinética , Peroxidação de Lipídeos , Peróxidos Lipídicos/química , Micelas , Oxirredução
19.
Phytomedicine ; 71: 153233, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32454348

RESUMO

BACKGROUND: Xanthohumol is known to exert anti-inflammatory properties but has poor oral bioavailability. Using advanced micellization technology, it has been possible to markedly enhance its bioavailability. PURPOSE: In the present study, we compared the chronic anti-inflammatory activities of native and micellar xanthohumol in the rat adjuvant arthritis model, using diclofenac as a reference drug. METHODS: Adjuvant arthritis was induced by injecting Freund's complete adjuvant into the right hind paw of rats and monitoring paw volume over 3 weeks. The drugs were given daily for 3 weeks, starting from the day of adjuvant inoculation. Serum was collected at the end of the experiment to measure inflammatory and oxidative stress parameters. Statistical comparisons between different groups were carried out by one-way analysis of variance followed by Tukey-Kramer multiple comparison test. RESULTS: Micellar solubilized xanthohumol showed a better anti-inflammatory activity than its native form. The reduction in paw volume was reflected in corresponding changes in relevant mediators of inflammation like tumor necrosis factor-α, interleukin-6 and C-reactive protein, myloperoxidase and lipid peroxidation markers. CONCLUSION: The findings confirm that micellar solubilization of xanthohumol enhances its anti-inflammatory activity, probably as a result of improving its bioavailabilty. The solubilized xanthohumol may prove to be a promising adjuvant tool for anti-inflammatory treatment and a potential anti-inflammatory alternative to synthetic drugs.


Assuntos
Anti-Inflamatórios/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Propiofenonas/química , Propiofenonas/farmacologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Artrite Experimental/tratamento farmacológico , Disponibilidade Biológica , Feminino , Flavonoides/farmacocinética , Adjuvante de Freund/efeitos adversos , Interleucina-6/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Micelas , Estresse Oxidativo/efeitos dos fármacos , Propiofenonas/farmacocinética , Ratos Wistar , Solubilidade , Fator de Necrose Tumoral alfa/metabolismo
20.
Chemosphere ; 252: 126494, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32443261

RESUMO

We used five types of surfactants assisted with sodium salts, including sodium tartrate (ST), sodium chloride (SC), and humic acid sodium (HAS) as auxiliary agents for soil washing to remove diesel from contaminated soil. Decontamination enhancement of diesel polluted soil washing with biosurfactant and H2O2 was examined, which showed higher effectiveness for newly contaminated soil. An increase in temperature and sodium salt addition exhibited a profound enhancement in diesel removal from aged contaminated soils. Compared to ST and SC, HAS exhibited a higher removal efficiency with saponin washing for aged diesel contaminated soil by lowering surface tension, shifting zeta potential, and increasing the number of micelles. Phytotoxicity experiments showed no significant inhibition of germination of lettuce, arugula, and cucumber with 0.2 g L-1 saponin incubation. Conversely, there was a promotion on the root extension of lettuce and cucumber except for arugula. Similarly, the addition of 2% HAS (wight of saponin) improved on root growth of lettuce, arugula, and cucumber, increasing by 25%, 5%, and 22% at the period of 14 d, respectively. Because of excellent removal efficiency and non-toxicity, enhanced wash with saponin and HAS might be considered in the future design of full-scale remediation processes of diesel contaminated soil.


Assuntos
Recuperação e Remediação Ambiental/métodos , Poluentes do Solo/química , Tensoativos/química , Poluição Ambiental , Substâncias Húmicas , Peróxido de Hidrogênio , Micelas , Solo , Poluentes do Solo/análise
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