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1.
J Cosmet Sci ; 70(3): 127-136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31398101

RESUMO

The impact that rhamnolipid (RL) and sophorolipid (SL) biosurfactants has on solution surface activity when used in conjunction with the commercially important zwitterionic surfactant cocamidopropyl betaine (CAPB) is highlighted for the first time through surface tension and surface rheology measurements on binary and ternary mixtures of these surfactants. It was observed that in both the binary (CAPB/RL) and the ternary (CAPB/RL/SL) mixtures, RL tends to dominate at the air-water interface and primarily control both surface tension and surface elasticity behavior. Significant reduction of surface tension and enhancement of surface elasticity is observed as a result of the competitive adsorbtion/dominance of the RL at the air-water interface and this leads to performance enhancements in terms of foam stability.


Assuntos
Micelas , Tensoativos/química , Reologia , Tensão Superficial , Água
2.
J Biomed Nanotechnol ; 15(10): 2045-2058, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462370

RESUMO

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity in vivo and in vivo than DOX-loaded micelles made from the commonly used material mPEG-PCL. Under laser irradiation, the photosensitizing protoporphyrin of DOX/PTPP produces abundant reactive oxygen species (ROS) that directly kill tumor cells as well as destroy the micelles themselves, leading to drug release. The ROS and DOX then act synergistically against the tumors. These ROS-responsive, laser-sensitive polymeric micelles may be useful for combining PDT and chemotherapy.


Assuntos
Espécies Reativas de Oxigênio/química , Doxorrubicina , Liberação Controlada de Fármacos , Micelas , Fotoquimioterapia , Polímeros
3.
Chem Commun (Camb) ; 55(69): 10226-10229, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31380870

RESUMO

A formulation of self-assembled peptido-nanomicelles has been developed for a combinational treatment of SDT, PDT and chemotherapy to nasopharyngeal carcinoma. In vitro cellular tests and in vivo mice therapy proved effective for targeted tumor growth inhibition. These merits provided a novel approach to non-invasive cancer treatments.


Assuntos
Corantes Fluorescentes/uso terapêutico , Carcinoma Nasofaríngeo/terapia , Peptídeos/uso terapêutico , Rosa Bengala/uso terapêutico , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Corantes Fluorescentes/administração & dosagem , Humanos , Camundongos Nus , Micelas , Carcinoma Nasofaríngeo/patologia , Peptídeos/administração & dosagem , Fotoquimioterapia/métodos , Rosa Bengala/administração & dosagem , Terapia por Ultrassom/métodos
4.
Int J Nanomedicine ; 14: 5527-5540, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413561

RESUMO

Background: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice. Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis. Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (~93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi. Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.


Assuntos
Aminopiridinas/química , Benzamidas/química , Ácido Fólico/uso terapêutico , Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofila/análogos & derivados , Clorofila/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Ácido Fólico/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Espécies Reativas de Oxigênio/metabolismo
5.
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
6.
Chemistry ; 25(50): 11635-11640, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31368214

RESUMO

Disulfide-containing detergents (DCDs) are introduced, which contain a disulfide bond in the hydrophobic tail. DCDs form smaller micelles than corresponding detergents with linear hydrocarbon chains, while providing good solubilization and reconstitution of membrane proteins. The use of this new class of detergents in structural biology is illustrated with solution NMR spectra of the human G protein-coupled receptor A2A AR, which is an α-helical protein, and the ß-barrel protein OmpX from E. coli.


Assuntos
Proteínas da Membrana Bacteriana Externa/química , Detergentes/química , Proteínas de Escherichia coli/química , Hidrolases/química , Receptor A2A de Adenosina/química , Proteínas da Membrana Bacteriana Externa/metabolismo , Dissulfetos/química , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Hidrolases/metabolismo , Micelas , Ressonância Magnética Nuclear Biomolecular , Estabilidade Proteica , Receptor A2A de Adenosina/metabolismo
7.
J Photochem Photobiol B ; 197: 111544, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31295716

RESUMO

Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in dermatological practices such as treatment of skin cancers. Clearance rate depends on different factors such as light irradiation, skin oxygenation and drug penetration. The poor penetration of 5-aminolevulinic acid (5-ALA) with topical application is limited and restrains the production of PpIX which could restrict PDT outcomes. This review will focus on techniques already used to enhance drug penetration in human skin, and will present their results, advantages, and drawbacks. Chemical and physical pretreatments will be discussed. Chemical pre-treatments comprise of drug formulation modification, use of agents that modify the heme cycle, enhance PpIX formation, and the combination of differentiation-promoting agent prior to PDT. On the other hand, physical pretreatments affect the skin barrier by creating holes in the skin or by removing stratum corneum. To promote drug penetration, iontophoresis and temperature modulation are interesting alternative methods. Cellular mechanisms enrolled during chemical or physical pretreatments have been investigated in order to understand how 5-ALA penetrates the skin, why it is preferentially metabolized in PpIX in tumour cells, and how it could be accumulated in deeper skin layers. The objective of this review is to compare clinical trials that use innovative technology to conventional PDT treatment. Most of these pretreatments present good or even better clinical outcomes than usual PDT.


Assuntos
Fármacos Fotossensibilizantes/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/química , Ácido Aminolevulínico/metabolismo , Ácido Aminolevulínico/uso terapêutico , Composição de Medicamentos , Humanos , Lipossomos/química , Micelas , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Protoporfirinas/química , Protoporfirinas/metabolismo , Protoporfirinas/uso terapêutico , Neoplasias Cutâneas/patologia
8.
Biomater Sci ; 7(9): 3898-3905, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31317137

RESUMO

To target a response to a high oxidative stress environment of inflammatory or tumor sites, various reactive oxygen species (ROS) sensitive polymers have been developed as drug delivery systems. In this study, a novel oxidation sensitive copolymer, phenylboronic acid pinacol ester-functionalized methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), was designed and synthesized by ring-opening alternating copolymerization (ROAP) and click reaction. The copolymers could self-assemble into micelles in aqueous solution with an average size of 20.3 ± 9.3 nm, and are able to load hydrophobic anticancer drug (doxorubicin, DOX) with a high encapsulation efficiency of 75.2%. Interestingly, the encapsulated drug showed accelerated release in the trigger of H2O2, or at low pH values. The copolymers have low cytotoxicity indicated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay towards 4T1 cells, which showed cell viabilities of more than 80% with treatment of our copolymers at concentrations up to 0.5 mg mL-1. The effective uptake of the drug-loaded micelles by 4T1 cells was investigated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) analysis. Finally, compared with free DOX, the DOX-loaded nanoparticles exhibited a better antitumor effect and had lower systemic toxicity in 4T1 tumor-bearing mice. Therefore, this new kind of copolymer acting as a stimuli-responsive nanocarrier should represent a promising therapeutic platform for cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Ácidos Borônicos/química , Doxorrubicina/administração & dosagem , Nanocápsulas/química , Polímeros/química , Animais , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Ésteres/química , Humanos , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Micelas , Oxirredução , Polietilenoglicóis/química
9.
Int J Nanomedicine ; 14: 4649-4666, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303753

RESUMO

Introduction: Herein, a hyaluronic acid (HA)-coated redox-sensitive chitosan-based nanoparticle, HA(HECS-ss-OA)/GA, was successfully developed for tumor-specific intracellular rapid delivery of gambogic acid (GA). Materials and methods: The redox-sensitive polymer, HECS-ss-OA, was prepared through a well-controlled synthesis procedure with a satisfactory reproducibility and stable resulted surface properties of the assembled cationic micelles. GA was solubilized into the inner core of HECS-ss-OA micelles, while HA was employed to coat outside HECS-ss-OA/GA for CD44-mediated active targeting along with protection from cation-associated in vivo defects. The desirable redox-sensitivity of HA(HECS-ss-OA)/GA was demonstrated by morphology and particle size changes alongside in vitro drug release of nanoparticles in different simulated reducing environments. Results: The results of flow cytometry and confocal microscopy confirmed the HA-receptor mediated cellular uptake and burst drug release in highly reducing cytosol of HA(HECS-ss-OA)/GA. Consequently, HA(HECS-ss-OA)/GA showed the highest apoptosis induction and cytotoxicity over the non-sensitive (HA(HECS-cc-OA)/GA) and HA un-coated (HECS-ss-OA/GA) controls against A549 NSCLC model both in vitro and in vivo. Furthermore, a diminished systemic cytotoxicity was observed in HA(HECS-ss-OA)/GA treated mice compared with those treated by HA un-coated cationic ones and GA solution.


Assuntos
Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Hialurônico/química , Micelas , Neoplasias/tratamento farmacológico , Xantonas/administração & dosagem , Xantonas/uso terapêutico , Células A549 , Animais , Antineoplásicos/farmacologia , Apoptose , Varredura Diferencial de Calorimetria , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/síntese química , Humanos , Ácido Hialurônico/síntese química , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Neoplasias/patologia , Oxirredução , Propionatos/síntese química , Propionatos/química , Espectroscopia de Prótons por Ressonância Magnética , Reprodutibilidade dos Testes , Distribuição Tecidual/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Xantonas/farmacologia
10.
Soft Matter ; 15(30): 6190-6199, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31328216

RESUMO

The evaporation of colloidal solutions is frequently observed in nature and in everyday life. The investigation of the mechanisms taking place during the desiccation of biological fluids is currently a scientific challenge with potential biomedical and industrial applications. In the last few decades, seminal works have been performed mostly on dried droplets of saliva, urine and plasma. However, the full understanding of the drying process in biocolloids is far from being achieved and, notably, the impact of solute properties on the morphological characteristics of the evaporating droplets, such as colloid segregation, skin formation and crack pattern development, is still to be elucidated. For this purpose, the use of model colloidal solutions, whose rheological behavior is more easily deducible, could represent a significant boost. In this work, we compare the drying of droplets of whey proteins and casein micelles, the two main milk protein classes, to that of dispersions of silica particles and polymer-coated silica particles, respectively. The mechanical behavior of such biological colloids and model silica dispersions was investigated through the analysis of crack formation, and the measurements of their mechanical properties using indentation testing. The study reveals numerous analogies between dairy and the corresponding model systems, thus confirming the latter as a plausible powerful tool to highlight the signature of the matter at the molecular scale during the drying process.


Assuntos
Caseínas/química , Laticínios/análise , Dessecação , Micelas , Proteínas do Soro do Leite/química , Fenômenos Mecânicos , Modelos Químicos , Reologia
11.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2244-2250, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359649

RESUMO

PUE@PEG-PLGA micelles has excellent characteristics such as small particle size, high drug loading and slow drug release. The results of TEM electron microscopy showed that PUE@PEG-PLGA micelles had obvious core-shell structure. The critical micelle concentration(CMC) of PEG-PLGA micelles determined by pyrene assay was about 4.8 mg·L~(-1). Laser confocal experiments showed that PEG-PLGA micelles can enhance the cellular uptake of coumarin-6 and aggregate around the mitochondria; quantitative results of extracellular drug residues also indirectly confirmed that PEG-PLGA micelles can promote cellular uptake of the drug. Acute ischemic myocardial model rats were prepared by coronary artery ligation, and then the model rats were randomly divided into six groups: Sham operation group, model group, puerarin(PUE) group, as well as low-, mid-, and high-dose PUE@PEG-PLGA micelles groups. Drugs were given by iv administration 5 min after the ligation. The ST segment changes in the electrocardiogram were monitored; serum creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels were detected and myocardial infarct size was also measured. Both PUE and PUE@PEG-PLGA micelles can reduce the elevated ST segment, reduce serum CK, LDH, AST and MDA levels, and reduce myocardial infarct size. The efficacy of PUE@PEG-PLGA medium and high dose groups was significantly better than that in the PUE group, and the efficacy in PUE@PEG-PLGA low dose group was basically equivalent to that in the PUE group. PUE@PEG-PLGA micelles can greatly improve the cardiomyocytes uptake of PUE, enhance the anti-acute myocardial ischemia effect of drugs, and reduce its dosage.


Assuntos
Isoflavonas/farmacologia , Micelas , Isquemia Miocárdica/tratamento farmacológico , Animais , Poliésteres , Polietilenoglicóis , Distribuição Aleatória , Ratos
12.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2251-2259, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359650

RESUMO

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-ß-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Neoplasias Pulmonares/patologia , Nanopartículas , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Micelas , Tamanho da Partícula , Taxoides
13.
J Agric Food Chem ; 67(33): 9232-9240, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31347839

RESUMO

The hydrophobic wax layer of pepper fruit (Capsicum frutescens L.) increases the importance of selecting adjuvants that improve the wetting property of droplets on the target organism and increase the effective utilization of fungicides. In this study, the effect of adjuvants including nonionic, cationic, organosilicone, and oils on the wettability of fungicides was determined. The critical micelle concentrations for S903 (organosilicone), 1227 (cationic), AEO-5 (nonionic), GY-Tmax (oil), and XP-2 (oil) were 25, 1000, 100, 200, and 500 mg/L, respectively. Interface behaviors and in vivo tests suggested that adjuvants at appropriate concentrations (S903, 2.5 mg/L; 1227, 100 mg/L; AEO-5, 1 mg/L; GY-Tmax, 50 mg/L; and XP-2, 5 mg/L) resulted in optimum efficiency. Adjuvants significantly increased the inhibitory activity of pyraclostrobin against the mycelial growth, spore germination, and germ tube elongation of Colletotrichum scovillei by 41.3-58.8%, 28.2-44.6%, and 27.8-39.8%, respectively. Pyraclostrobin amended with S903 and XP-2 showed higher efficacy against anthracnose than the fungicide alone on pepper fruit. The increased efficacy may have resulted from the changed crystal morphology (ellipses of similar sizes), improved wettability, and rainfastness. A structural equation model indicated that surface tension and retention play the most important roles in the application properties of fungicide. In field experiments, the efficacy of pyraclostrobin with adjuvants showed no significant difference with pyraclostrobin alone, which indicated that, except for adjuvants, other spraying technologies are important for improving the field performance of fungicides. These results provide a foundation for the synthesis of highly efficient fungicides based on crystal structure and for the sustainable management of pepper anthracnose.


Assuntos
Portadores de Fármacos/química , Fungicidas Industriais/química , Estrobilurinas/química , Capsicum/microbiologia , Colletotrichum/efeitos dos fármacos , Colletotrichum/crescimento & desenvolvimento , Cristalização , Frutas/microbiologia , Fungicidas Industriais/farmacologia , Micelas , Compostos de Organossilício/química , Doenças das Plantas/microbiologia , Estrobilurinas/farmacologia , Molhabilidade
14.
Chemistry ; 25(54): 12601-12610, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31291028

RESUMO

Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug-loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra-high curcumin loading exceeding 50 wt.%, while the other allows a drug loading of only 25 wt.%. In the low capacity micelles, steady-state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time-resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high-capacity micelles, preventing an observable emission in steady-state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles.


Assuntos
Antineoplásicos/química , Corantes/química , Curcumina/química , Portadores de Fármacos/química , Micelas , Polímeros/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Luz , Tamanho da Partícula , Solubilidade , Espectrometria de Fluorescência , Temperatura Ambiente
15.
AAPS PharmSciTech ; 20(6): 245, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286294

RESUMO

Highly water-soluble prodrug micelle (50-fold compared with free MTX) of methotrexate-polyethyleneglycol-rhodamine (MTX-PEG-rhodamine) and MTX-mPEG was synthesized by the esterification reaction. The stability of the prodrug micelles was evaluated in phosphate buffer saline (PBS) with 10% fetal bovine serum (FBS). The tumor volume of the saline, MTX, and MTX-PEG-rhodamine groups was increased 3.7-fold, 2.8-fold, and 1.8-fold, respectively, compared with the initial tumor volume. TUNEL and drug distribution results further confirmed that the micelle of MTX-PEG-rhodamine possessed fewer side effects on the normal tissue compared with MTX. The prodrug micelle showed four advantages: retention of the drug activity site, higher water solubility of methotrexate (MTX), ease of preparation and application, and preferential accumulation in tumor tissues. These advantages of MTX-mPEG make it a promising drug delivery system (DDS) for clinical use.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Metotrexato/farmacologia , Micelas , Polietilenoglicóis/química , Pró-Fármacos/farmacologia , Rodaminas/química , Água/química , Animais , Antimetabólitos Antineoplásicos/química , Sistemas de Liberação de Medicamentos , Feminino , Metotrexato/química , Camundongos , Camundongos Nus , Neoplasias/tratamento farmacológico , Pró-Fármacos/química , Solubilidade , Ensaios Antitumorais Modelo de Xenoenxerto
16.
AAPS PharmSciTech ; 20(7): 254, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31317354

RESUMO

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


Assuntos
Curcumina/administração & dosagem , Curcumina/farmacocinética , Olho/metabolismo , Micelas , Nanoestruturas , Administração Oftálmica , Antioxidantes/química , Disponibilidade Biológica , Óleo de Rícino/química , Linhagem Celular , Curcumina/farmacologia , Preparações de Ação Retardada , Humanos , Estresse Oxidativo/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Phys Chem Chem Phys ; 21(28): 15400-15407, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31271395

RESUMO

A biomimetic membrane formed by hybrid Janus dendrimers (JDs) which contain hydrogenated and fluorinated dendrons was explored by dissipative particle dynamics simulations. The JD membrane is bilayered and shows a bicontinuous morphology which is also observed in nano-sized dendrimersomes. The thickness of the dendrimersome is significantly less than that of the planar membrane. The co-assembly of lipids with JDs to develop a hybrid membrane was studied as well. Lipids tend to locate in the hydrocarbon domain of the bicontinuous structure of the JD-rich membrane, while 2-dimensional micelles of JDs float in the leaflet of the lipid-rich membrane. The microstructure of the hybrid membrane was quantified by interdigitation lengths in the hydrocarbon, fluorocarbon, and lipid domains. Finally, the influence of lipid concentration on lipid fluidity was examined in terms of lipid diffusivity, which is found to be closely associated with the membrane microstructure.


Assuntos
Dendrímeros/química , Flúor/química , Lipídeos/química , Membranas Artificiais , Simulação por Computador , Hidrogenação , Micelas
18.
J Agric Food Chem ; 67(26): 7416-7427, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31180666

RESUMO

The core-shell structured micelles from octenylsuccinated oat ß-glucan (OSßG) are able to solubilize ß-carotene (ßC). This study reveals molecular interactions governing the formation, stabilization, and ßC uptake of OSßG micelles (OSßG-Ms) by means such as water contact angle, 1H nuclear magnetic resonance, dynamic light scattering, and confocal laser scanning microscopy. The results indicated that the micellization of OSßG molecules is triggered by hydrophobic interactions between octenylsuccinate (OSA) moieties, while OSßG-Ms are stabilized via both hydrophobic interactions and hydrogen bonds. For their uptake of ßC, ßC molecules are first adsorbed onto OSßG-Ms by interacting with OSA moieties scattered on micelle surface. By further interacting with OSA moieties located in micelle shell, ßC molecules travel across the shell and finally are trapped in the hydrophobic core. In simulated gastrointestinal fluids, ßC is controlled released from OSßG-Ms as an integrated consequence of its diffusion as well as the swelling and erosion of OSßG-Ms. As a result, this study first uncovered the mechanism underlying the uptake of ßC by OSßG-Ms, which will certainly facilitate the effective loading of hydrophobic ingredients by OSßG-Ms.


Assuntos
Avena/química , Preparações de Ação Retardada/química , Extratos Vegetais/química , Succinatos/química , beta Caroteno/química , beta-Glucanas/química , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Ressonância Magnética , Micelas , Estrutura Molecular
19.
Phys Chem Chem Phys ; 21(24): 13005-13013, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31165825

RESUMO

Cubosomes and hexosomes are emerging platforms for drug and nutraceutical delivery applications. In addition to common high- and low-energy batch emulsification methods for the preparation of these nano-self-assemblies, it is important to introduce suitable microfluidic devices with a precision control of the flow parameters for their continuous production. Microfluidics has several advantages including cost effectiveness, short-production time, and control of the nanoparticle size and size distribution. In the present study, a hydrodynamic flow focusing polyimide microfluidic device was employed for the continuous production of hexosomes based on docosahexaenoic acid monoglyceride (MAG-DHA), in the presence of the stabilizer Pluronic F127. The size, structural, morphological and size characterizations of the continuously produced MAG-DHA nanodispersions were investigated through an integrated approach involving synchrotron small angle X-ray scattering, dynamic light scattering, and cryogenic transmission electron microscopy. We report on a simple process for the microfluidic synthesis of hexosomes with sizes ranging from 108 to 138 nm and relatively narrow size distributions as the polydispersity indices were in the range of 0.14-0.22. At the applied total volumetric flow rates (TFRs) ranging of 50-150 µL min-1 and flow rate ratios (FRRs) of 10-30, it was evident from SAXS findings that ethanol has only a slight effect on the lattice parameter of the internal inverse hexagonal (H2) phase of the produced hexosomes. In addition to hexosomes, cryo-TEM observations indicated the coexistence of vesicular structures and smaller nano-objects. The formation of these nano-objects that are most likely normal micelles was also confirmed by SAXS, particularly on increasing FRR from 10 to 20 or 30 at TFR of 150 µL min-1. Taking into account the reported positive health effects of MAG-DHA, which is a long-chain omega-3 (ω-3) polyunsaturated fatty acid (PUFA) monoglyceride, in various disorders including cancer, the produced hexosomes are attractive for the delivery of ω-3 PUFAs, drugs, nutraceuticals, and their combinations.


Assuntos
Ácidos Docosa-Hexaenoicos/química , Ácidos Graxos Ômega-3/química , Dispositivos Lab-On-A-Chip , Nanopartículas/química , Hidrodinâmica , Micelas , Monoglicerídeos/química , Tamanho da Partícula , Poloxâmero/química
20.
Int J Nanomedicine ; 14: 3629-3644, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190816

RESUMO

Background: A very common and simple method (known as the blending method) to formulate drug delivery systems with required properties is to physically mix amphiphilic block copolymers with different hydrophobicity. In addition to its simplicity, this blending strategy could help avoid the time and effort involved in the synthesis of block copolymers with the desired structure required for specific drug formulations. Purpose: We used the blending strategy to design a system that could overcome the problem of high hydrophobicity and be a good candidate for drug product development using PEG-PLA-PEG triblock copolymers. Methods: Two types of PEG-PLA-PEG triblock copolymers with similar (long) PLA molecular weights (MWs) and different PEG MWs were synthesized. The micellar formulations were prepared by blending the two block copolymers in various ratios. The size and stability of the blending systems were subsequently investigated to optimize the formulations for further studies. The loading properties of doxorubicin or paclitaxel into the optimized blending system were compared to that in mono systems (systems composed of only a single type of triblock copolymer). In vitro and in vivo anti-cancer effects of the preparations were evaluated to assess the use of the blending system as an optimal nanomedicine platform for insoluble anticancer agents. Results: The blending system (B20 system) with an optimized ratio of the triblock copolymers overcame the drawbacks of mono systems. Drug uptake from the drug-loaded B20 system and its anticancer effects against KB cells were superior compared to those of free drugs (doxorubicin hydrochloride and free paclitaxel). In particular, doxorubicin-loaded B20 resulted in extensive doxorubicin accumulation in tumor tissues and significantly higher in vivo anti-cancer effects compared to free doxorubicin. Conclusion: The blending system reported here could be a potential nanoplatform for drug delivery due to its simplicity and efficiency for pharmaceutical application.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Tamanho da Partícula , Polímeros/química , Animais , Antineoplásicos/farmacologia , Coloides/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Células KB , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Paclitaxel/farmacologia , Poliésteres/química , Polietilenoglicóis/química , Solubilidade , Distribuição Tecidual/efeitos dos fármacos
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