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1.
J Chromatogr A ; 1628: 461438, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32822978

RESUMO

A fast, simple, environmentally friendly and sensitive on-line concentration method using microemulsion system as background solution (BGS) was developed for the trace detection of propazine, atrazine, simazine in food samples. The electrokinetic injection assisted micelle to cyclodextrin stacking (MCDS) was designed for the enrichment of target compounds. The factors affected enrichment performance, such as the kind of CDs, the amount of CDs, the concentration of methanol in BGS, the concentration of micelle in sample matrix, the concentration of phosphoric acid in BGS and the sample injection time were optimized. The optimized electrophoretic condition was obtained as following: 50 mM α-CD, 20 mM SDS in sample matrix., 80 mM PA and 20% MeOH (v/v) in BGS, sample solution by electrokinetic injection at -10 kV for 80 s. Under the optimized conditions described above, the linear range was 0.1-20 ug/mL with a good linear relationship with a correlation coefficient (r) ≥ 0.9985. The SEFs for the propazine, atrazine, simazine were found to be 123, 85 and 62 respectively. The proposed MCDS-MEEKC method provided an efficient method for trace analysis of triazine herbicides in honey and dendrobium officinale samples.


Assuntos
Técnicas de Química Analítica/métodos , Cromatografia Capilar Eletrocinética Micelar , Ciclodextrinas/química , Herbicidas/isolamento & purificação , Micelas , Triazinas/isolamento & purificação , Atrazina , Ácidos Fosfóricos , Simazina
2.
Int J Nanomedicine ; 15: 3851-3868, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764919

RESUMO

Purpose: The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(ß-amino ester) (mPEG-PBAE). Materials and Methods: We synthesized four different mPEG-PBAE copolymers using mPEG-NH2 with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG5000-PBAE-C12 polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo. Results: The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC50 of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation. Conclusion: The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Catecóis/química , Catecóis/farmacologia , Micelas , Polietilenoglicóis/química , Polímeros/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Catecóis/farmacocinética , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Tamanho da Partícula , Distribuição Tecidual
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.
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
5.
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
6.
Nat Protoc ; 15(9): 2980-3008, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32839575

RESUMO

High-surface-area mesoporous materials expose abundant functional sites for improved performance in applications such as gas storage/separation, catalysis, and sensing. Recently, soft templates composed of amphiphilic surfactants and block copolymers have been used to introduce mesoporosity in various materials, including metals, metal oxides and carbonaceous compounds. In particular, mesoporous metals are attractive in electrocatalysis because their porous networks expose numerous unsaturated atoms on high-index facets that are highly active in catalysis. In this protocol, we describe how to create mesoporous metal films composed of gold, palladium, or platinum using block copolymer micelle templates. The amphiphilic block copolymer micelles are the sacrificial templates and generate uniform structures with tunable pore sizes in electrodeposited metal films. The procedure describes the electrodeposition in detail, including parameters such as micelle diameters, deposition potentials, and deposition times to ensure reproducibility. The micelle diameters can be controlled by swelling the micelles with different solvent mixtures or by using block copolymer micelles with different molecular weights. The deposition potentials and deposition times allow further control of the mesoporous structure and its thickness, respectively. Procedures for example applications are included: glucose oxidation, ethanol oxidation and methanol oxidation reactions. The synthetic methods for preparation of mesoporous metal films will take ~4 h; the subsequent electrochemical tests will take ~5 h for glucose sensing and ~3 h for alcohol oxidation reaction.


Assuntos
Ouro/química , Paládio/química , Platina/química , Álcoois/química , Catálise , Técnicas de Química Sintética , Eletroquímica , Interações Hidrofóbicas e Hidrofílicas , Micelas , Modelos Moleculares , Conformação Molecular , Oxirredução , Polímeros/química
7.
J Oleo Sci ; 69(9): 1021-1030, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32788513

RESUMO

A novel jellyfish-shaped triazine hexamer quaternary ammonium chloride surfactant (TH12QC) was synthesized, which consisted of one triazine spacer group and six long flexible hydrophobic chains. The molecular structure and aggregation behavior of TH12QC was investigated by nuclear magnetic resonance (NMR), surface tension, electrical conductivity, dynamic light scattering (DLS), transmission electron microscope (TEM), etc. The results show that the jellyfish-shaped TH12QC has better surface activity and lower surface tension than traditional ionic and Gemini surfactants in aqueous solution. There are two inflection points in the curve of conductivity versus concentration of the TH12QC aqueous solution, which correspond to the critical aggregation concentration (CAC) and the critical micelle concentration (CMC) respectively. The existence of CAC indicates that there is a pre-aggregation process before TH12QC forms micelles. The results of DLS and TEM show that network pre-aggregation, spherical aggregation and dense spherical aggregation were observed in different concentration of TH12QC aqueous solution, and the electrostatic equilibrium of the system subtly depends on the concentration of the solution. In addition, intramolecular and intermolecular hydrogen bonding is also an important factor. This study provides a method for studying the aggregation behavior and morphology of oligomeric surfactants with rigid spacer groups.


Assuntos
Cloreto de Amônio/química , Cloreto de Amônio/síntese química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/síntese química , Tensoativos/química , Tensoativos/síntese química , Triazinas/química , Triazinas/síntese química , Fenômenos Químicos , Difusão Dinâmica da Luz , Condutividade Elétrica , Ligação de Hidrogênio , Micelas , Estrutura Molecular , Soluções , Tensão Superficial , Água/química
8.
Food Chem ; 332: 127440, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32652411

RESUMO

Rehydration in an alkaline solution has been shown to improve the rehydration behaviour of milk protein isolate (MPI). In this study, the focus is on citric acid neutralization of MPI powder dissolved in alkaline solution. The results showed that alkalization induced more negative zeta-potential compared to MPI control, reducing it from -22.4 mV to -32.6 mV. Neutralization had a relatively similar zeta-potential value as alkalized sample. Sodium carbonate addition increased pH and caused a consequential reduction of ionic calcium in aqueous phase and, neutralization caused a small increase in ionic calcium. Soluble aggregate of κ-casein protein and whey protein was suggested in alkalization and neutralization process by non-reducing SDS-PAGE. In addition, neutralization kept a stable colloidal particle size for pHs decreased to pH 9,8 and 7; however, alkalization and neutralization created casein aggregates of larger colloidal particle size than primary casein micelle in control MPI.


Assuntos
Cálcio/química , Caseínas/química , Quelantes/química , Animais , Bovinos , Ácido Cítrico/química , Concentração de Íons de Hidrogênio , Micelas , Tamanho da Partícula , Proteínas do Soro do Leite/química
9.
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
10.
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
11.
Med Hypotheses ; 143: 110081, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32653736

RESUMO

Hand hygiene by washing with soap and water is recommended for the prevention of COVID-19 spread. Soaps and detergents are explained to act by damaging viral spike glycoproteins (peplomers) or by washing out the virus through entrapment in the micelles. Technically, soaps come under a functional category of molecules known as surfactants. Surfactants are widely used in pharmaceutical formulations as excipients. We wonder why surfactants are still not tried for prophylaxis or therapy against COVID-19? That too when many of them have proven antiviral properties. Moreover, lung surfactants have already shown benefits in respiratory viral infections. Therefore, we postulate that surfactant-based prophylaxis and therapy would be promising. We believe that our hypothesis would stimulate debate or new research exploring the possibility of surfactant-based prophylaxis and therapy against COVID-19. The success of a surfactant-based technique would save the world from any such pandemic in the future too.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Tensoativos/farmacologia , Antivirais/administração & dosagem , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/transmissão , Humanos , Micelas , Modelos Biológicos , Antissépticos Bucais/administração & dosagem , Antissépticos Bucais/farmacologia , Pneumonia Viral/transmissão , Tensoativos/administração & dosagem
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.
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
14.
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
15.
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
16.
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
17.
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
18.
Food Chem ; 331: 127277, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32544653

RESUMO

A novel nanocomposite poly(ethylene-co-vinyl acetate) (EVA) film with controlled in vitro release of iprodione (ID) was prepared. Chitosan (CS) was used as the reinforcement which enhances the water and oxygen permeability of films. ID loaded poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) (IPP) micelles were used as the drug carrier which endows the films with antifungal and controlled release ability. IPP micelles with spherical shape and uniform size were obtained, and the maximum encapsulation efficacy (EE) was 91.17 ± 5.03% by well controlling the feeding amount of ID. Incorporation CS could improve the oxygen and moisture permeability of films, and the maximum oxygen permeability (OP) and water vapor transmission rate (WVTR) were 477.84 ± 13.03 cc/(m2·d·0.1 MPa) and 8.60 ± 0.25 g m-2 d-1, respectively. After loading IPP micelles, the films showed an improved antifungal ability and temperature-sensitive drug release behavior, and were found to enhance the quality of grapes by pre-harvest spraying.


Assuntos
Aminoimidazol Carboxamida/análogos & derivados , Hidantoínas/farmacocinética , Nanocompostos/química , Vitis/efeitos dos fármacos , Aminoimidazol Carboxamida/administração & dosagem , Aminoimidazol Carboxamida/farmacocinética , Quitosana/química , Preparações de Ação Retardada , Portadores de Fármacos , Microbiologia de Alimentos , Fungicidas Industriais/administração & dosagem , Fungicidas Industriais/farmacocinética , Hidantoínas/administração & dosagem , Lactonas/química , Micelas , Oxigênio , Permeabilidade , Polietilenoglicóis/química , Polivinil/química , Vapor
19.
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
20.
Ars pharm ; 61(2): 105-112, abr.-jun. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-191330

RESUMO

BACKGROUND: topical antiseptic agents have been used widely in normal skin and wound which is associated with side effects such as systemic toxicity. OBJECTIVE: Iodine is a non-metallic agent with an antimicrobial property that is used in the clinic as antiseptic. Iodophores such as Povidone-Iodine (PVP-I) introduced to improve the stability of the aqueous solution of iodine. Time taking and expensive procedures for producing complex between iodine and polyvinyl pyrolidine and systemic iodine absorption after topical PVP-I application are limitations on the application of this iodophore. The aim of this study was the design and evaluation of polymeric micelles for the overcoming of PVP-I limitations. METHODS: Eight polymeric micelle formulations prepared by the thin-layer method based on full-factori¬al DESIGN: In an ex-vivo study permeability of iodine- loaded in polymeric micelles through rat skin was evaluated in comparison with PVP-I. RESULTS: polymeric micelles demonstrated particle size between 14-153 nm that is affected by critical micelle concentration (CMC) and molecular weight of the polymer. Maximum % of drug released after 24 h was 62.3% that mainly controlled by the type of polymer. All polymeric micelles significantly decreased the percentage of drug permeated through rat skin and so decreased the risk of iodine toxicity. The minimum bactericidal concentration of polymeric micelles was comparable with PVP-I. CONCLUSIONS: Polymeric micelle demonstrated a perfect topical carrier for iodine loading and delivery through the skin by Iodine entrapment into the skin and sufficiently antimicrobial effect


ANTECEDENTES: los agentes antisépticos tópicos se han utilizado ampliamente en la piel y heridas normales, lo que se asocia con efectos secundarios como la toxicidad sistémica. OBJETIVO: el yodo es un agente no metálico con propiedades antimicrobiana que se usa en la clínica como antiséptico. Los yodóforos como la povidona yodada (PVP-I) son introducidos para mejorar la estabilidad de la solución acuosa de yodo. El tiempo y el procedimiento costoso para producir complejos entre yodo y polivinil pirolidina y la absorción sistémica de yodo después de la aplicación tópica de PVP-I son limitaciones en la aplicación de este yodóforo. El objetivo de este estudio fue el diseño y la evaluación de micelas poliméricas para superar las limitaciones de PVP-I. MÉTODOS: Ocho formulaciones de micelas poliméricas son preparadas por el método de capa delgada basado en un diseño factorial completo. En un estudio ex vivo, se evaluó la permeabilidad del yodo cargado en micelas poliméricas a través de la piel de rata en comparación con PVP-I. RESULTADOS: las micelas poliméricas demostraron un tamaño de partícula entre 14-153 nm que se vea fectado por la concentración crítica de micelas (CMC) y el peso molecular del polímero. El porcentaje máximo de fármaco liberado después de 24 h fue del 62,3% que se controla principalmente por el tipo de polímero. Todas las micelas poliméricas disminuyeron significativamente el porcentaje de fármaco permeado a través de la piel de rata y, por lo tanto, disminuyeron el riesgo de toxicidad por yodo. La concentración bactericida mínima de micelas poliméricas fue comparable con PVP-I. CONCLUSIÓN: la micela polimérica demostró ser un portador tópicovperfecto para la carga y entrega de yodo a través de la piel mediante el atrapamiento de yodo en la piel y un efecto antimicrobiano suficiente


Assuntos
Animais , Masculino , Ratos , Iodo/farmacocinética , Povidona-Iodo/farmacocinética , Micelas , Polímeros , Anti-Infecciosos Locais/farmacocinética , Fatores de Tempo , Ratos Wistar , Modelos Animais
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