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1.
Chem Commun (Camb) ; 55(67): 10015-10018, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31378791

RESUMO

We report the first neutral and water-soluble polymer capable of strong mitochondrial targeting in vitro and in vivo, zwitterionic poly[2-(N-oxide-N,N-diethylamino)ethyl methacrylate] (OPDEA). OPDEA is quickly internalized via macropinocytosis by various cancer cells and transferred into the mitochondria, which slightly lowers the mitochondrial membrane potential as determined by the JC-1 assay.


Assuntos
Mitocôndrias/metabolismo , Ácidos Polimetacrílicos/química , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Potencial da Membrana Mitocondrial , Camundongos , Imagem Óptica/métodos , Permeabilidade , Ácidos Polimetacrílicos/metabolismo , Solubilidade , Água
2.
Life Sci ; 234: 116770, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421085

RESUMO

Aim Licoricidin has multiple pharmacological activities. The present study was designed to investigate the permeability and pharmacokinetic behavior of licoricidin using in vitro models. MATERIAL AND METHODS: First, human liver microsomes and recombinant human supersomes were used to investigate the interactions between metabolic enzymes and licoricidin. In addition, rat, minipig, rabbit, dog, monkey, and human liver microsomes were used to determine metabolic differences among species. The parallel artificial membrane permeability assay (PAMPA) was used to explore licoricidin permeability behavior. KEY FINDINGS: At 100 µM, licoricidin strongly inhibited CYP2C9, CYP2C19, CYP3A4, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15, and UGT2B17. Licoricidin metabolism exhibited considerable differences among species; dog, pig, and rat liver microsomes showed higher metabolic capacity than the other species. Seven licoricidin metabolites were identified by liquid chromatography-tandem mass spectrometry, and hydration and hydroxylation were the major metabolic pathways. The PAMPA permeability of licoricidin was moderate at both pH 4.0 and 7.4. SIGNIFICANCE: The present study will support further pharmacological or toxicological research on licoricidin.


Assuntos
Benzopiranos/metabolismo , Benzopiranos/farmacocinética , Animais , Inibidores das Enzimas do Citocromo P-450/metabolismo , Inibidores das Enzimas do Citocromo P-450/farmacocinética , Sistema Enzimático do Citocromo P-450/metabolismo , Cães , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/metabolismo , Haplorrinos , Humanos , Redes e Vias Metabólicas , Microssomos Hepáticos/metabolismo , Permeabilidade , Coelhos , Ratos , Especificidade da Espécie , Suínos , Porco Miniatura
3.
J Chem Phys ; 151(7): 074903, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438701

RESUMO

Ionic microgels are soft colloidal particles, composed of crosslinked polymer networks, which ionize and swell when dispersed in a good solvent. Swelling of these permeable, compressible particles involves a balance of electrostatic, elastic, and mixing contributions to the single-particle osmotic pressure. The electrostatic contribution depends on the distributions of mobile counterions and coions and of fixed charge on the polymers. Within the cell model, we employ two complementary methods to derive the electrostatic osmotic pressure of ionic microgels. In Poisson-Boltzmann (PB) theory, we minimize a free energy functional with respect to the electrostatic potential to obtain the bulk pressure. From the pressure tensor, we extract the electrostatic and gel contributions to the total pressure. In a statistical mechanical approach, we vary the free energy with respect to microgel size to obtain exact relations for the microgel electrostatic osmotic pressure. We present results for planar, cylindrical, and spherical geometries. For models of membranes and microgels with fixed charge uniformly distributed over their surface or volume, we derive analogs of the contact value theorem for charged colloids. We validate these relations by solving the PB equation and computing ion densities and osmotic pressures. When implemented within PB theory, the two methods yield identical electrostatic osmotic pressures for surface-charged microgels. For volume-charged microgels, the exact electrostatic osmotic pressure equals the average of the corresponding PB profile over the gel volume. We demonstrate that swelling of ionic microgels depends on the variation of the electrostatic pressure inside the particle and discuss implications for interpreting experiments.


Assuntos
Modelos Teóricos , Pressão Osmótica , Géis , Permeabilidade , Eletricidade Estática , Termodinâmica
4.
Biomater Sci ; 7(9): 3581-3593, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31265011

RESUMO

Nanomedicine has shown remarkable progress in preclinical studies of tumor treatment. Over the past decade, scientists have developed various nanocarriers (NCs) for delivering drugs into the tumor area. However, the average amount of accumulated drugs in tumor sites is far from satisfactory. This limitation is strongly related to the corona formation during blood circulation. To overcome this issue, NCs should be designed to become highly stealthy by modifying their surface charge. However, at the same time, stealthy effects not only prevent protein formation but also alleviate the cellular uptake of NCs. Therefore, it is necessary to develop NCs with switchable properties, which are stealthy in the circulation system and sticky when arriving at tumor sites. In this review, we discuss the recent strategies to develop passive and active charge-switchable NCs, known as chameleon-like drug delivery systems, which can reversibly transform their surface from stealthy to sticky and have various designs.


Assuntos
Antineoplásicos/administração & dosagem , Nanocápsulas/química , Animais , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Nanomedicina/métodos , Tamanho da Partícula , Permeabilidade , Polímeros/química , Propriedades de Superfície
5.
Food Chem ; 298: 125041, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31261000

RESUMO

Edible packaging films play an important role in extending the shelf life of food products. In this work, the properties of cellulose nanofiber (CNF) reinforced hemicelluloses/chitosan-based edible films with xylooligosaccharides (XOS) have been evaluated. Results showed that the tensile strength (TS) of the film can be increased by 2.5 times with adding 5 wt% CNF. Incorporating 1.79-7.18% XOS into hemicelluloses-chitosan matrix only caused slightly higher water vapor permeability, and the composite films exhibited good hydrophobicity, thermal stability, and high transparency. The hemicelluloses/chitosan films with 1.79-5.38% XOS had higher TS (42.7-50.7 MPa) and lower oxygen permeability (OP, 4.95-5.06 cm3 µm/m2·day·kPa) than those containing 7.18% XOS. Additionally, ∼92.6% XOS in films can be released in simulated gastric fluid within 60 min. Overall, XOS (1.79-5.38%) with prebiotic properties can be added to films successfully to improve the functionality and the films were fit for food-packaging where high TS and low OP are required.


Assuntos
Celulose/química , Quitosana/química , Glucuronatos/química , Nanofibras/química , Oligossacarídeos/química , Embalagem de Alimentos/métodos , Suco Gástrico , Humanos , Microscopia Eletrônica de Varredura , Permeabilidade , Polissacarídeos/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Vapor , Resistência à Tração , Difração de Raios X
6.
J Agric Food Chem ; 67(33): 9277-9285, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31353906

RESUMO

3,3'-Diindolylmethane (DIM), a digestive metabolite originating from cruciferous vegetables, has dietary potential for the treatment of various human intestinal diseases. Although intestinal permeability dysfunction is closely related to the initiation and progression of human intestinal inflammatory diseases (IBDs), the effect of DIM on intestinal permeability is unclear. We evaluated the effect of DIM on the intestinal permeability of human intestinal cell monolayers and the animal model Caenorhabditis elegans, which were treated with IL-1ß and Pseudomonas aeruginosa, respectively, to mimic IBD conditions. DIM substantially restored the intestinal permeability of differentiated Caco-2 cells by enhancing the expression of tight junction proteins (including occludin and ZO-1). Compared to the IL-1ß single treatment (551.0 ± 49.0 Ω·cm2), DIM (10 µM) significantly increased the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers (919.0 ± 66.4 Ω·cm2, p < 0.001). DIM also ameliorated the impaired intestinal permeability and extended the lifespan of C. elegans fed P. aeruginosa. The mean lifespan of DIM-treated worms (10.8 ± 1.3 days) was higher than that of control-treated worms (9.7 ± 1.1 days, p < 0.01). Thus, DIM is a potential nutraceutical candidate for the treatment of leaky gut syndrome by improving intestinal permeability.


Assuntos
Indóis/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Animais , Células CACO-2 , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Mucosa Intestinal/metabolismo , Intestinos , Masculino , Ocludina/genética , Ocludina/metabolismo , Permeabilidade/efeitos dos fármacos , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
7.
Water Sci Technol ; 79(11): 2068-2078, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31318344

RESUMO

A simple and efficient route was used to prepare an amphiphilic copolymer (poly(propylene glycol)-co-poly(ethylene glycol)-co-poly(propylene glycol)) (PPG-co-PEG-co-PPG) by one-pot polymerization reaction. This copolymer was used as the hydrophilic additive in preparation of poly(vinylidene fluoride) (PVDF) ultrafiltration membranes via immersion-precipitation process. Surface characteristics of the membranes were confirmed by contact angle measurements, zeta potential, attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy and atomic force microscopy. During filtration experiments, the modified membranes showed better permeation and antifouling performances compared to PVDF membranes with bovine serum albumin, sodium alginate and yeast. After hydraulic stirring cleaning with deionized water, water flux recovery and rejection ratio of the modified membranes were higher than those of pristine PVDF membrane, and the flux recovery ratio was maximized at 94.29%. It was suggested that PPG-co-PEG-co-PPG copolymer was anchored in the PVDF membrane through the two hydrophobic ends of PPG blocks, while the hydrophilic intermediate of the PEG block segregated onto the membrane or pore surface during the membrane preparation process. The synthesized method of amphiphilic PPG-co-PEG-co-PPG copolymer paved a novel way to solve the problems of less compatibility between the copolymer and membrane matrix and instability with water molecules in the ultrafiltration process.


Assuntos
Membranas Artificiais , Ultrafiltração/métodos , Permeabilidade , Polivinil
8.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2486-2492, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359715

RESUMO

To establish a determination method for the contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid of Baimai Ointment,and investigate the percutaneous permeability of Baimai Ointment and the effects of two kinds of penetration enhancers on percutaneous absorption of three components. The contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid were determined by high pressure liquid chromatography( HPLC). The vertical modified Franz diffusion cell was used to perform a transdermal experiment in vitro with the abdominal skin of mice( treated and untreated). The transdermal receptor liquid was preferably used to investigate the transdermal absorption rule of the Baimai Ointment and the effect of the penetration enhancer. The results showed that the comprehensive solubility of PEG-ET-NS( 3 ∶3 ∶4) was best among three types of receptor liquid PG-ET-NS( 3 ∶3 ∶4),PEG-ET-NS( 3 ∶3 ∶4),ET-NS( 3 ∶7). PEG-ET-NS was used as the receptor liquid for in vitro transdermal experiments. The cumulative permeation area of ammonium glycyrrhetate,nardosinone and curcumin within 24 h was 5. 73,18. 99,0. 38 µg·cm~(-2)respectively. Taking QEFand ER as comprehensive evaluation indicators of permeation performance,the comprehensive penetration-promoting performance of ammonium glycyrrhizinate: 3% PEG 400-ethanol-normal saline ≈ 1. 19 times( 3%azone) = 1. 94 times( blank); comprehensive penetration-promoting performance of nardosinone: 3% PEG 400-ethanol-normal saline≈1. 28 times( 3% azone) = 1. 37 times( blank); the comprehensive penetration performance of curcumin: 3% PEG 400-ethanol-normal saline≈1. 77 times( 3% azone) ≈3. 42 times( blank). The comprehensive penetration enhancement properties of the two penetration enhancers were as follows: 3% PEG 400-ethanol-normal saline>3%azone>blank. The transdermal absorption curve of ammonium glycyrrhetate,nardosinone and curcumin in Baimai Ointment were consistent with the zero-order equation,indicating that the transdermal absorption process was irrelevant to the concentration of three components,and its was a diffusion process. This experiment provides reference for the study of ointment transdermal preparations.


Assuntos
Administração Cutânea , Pomadas/farmacocinética , Absorção Cutânea , Pele , Animais , Camundongos , Permeabilidade
9.
Drugs ; 79(12): 1277-1286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313100

RESUMO

ROS1 gene rearrangements exist in 1-2% of non-small cell lung cancers, typically occurring in younger, never or light smokers with adenocarcinoma. ROS1 gene fusions are potent oncogenic drivers, the presence of which results in the susceptibility of tumours to ROS1-targeted therapy. Crizotinib was the first tyrosine kinase inhibitor to demonstrate activity in ROS1-rearranged lung cancer, and remains the recommended first-line therapy for patients with advanced ROS1-rearranged non-small cell lung cancer. Despite excellent initial responses to crizotinib, the majority of patients develop disease progression, which may be intracranial or extracranial. Identification of resistance mechanisms to crizotinib, and newer generation tyrosine kinase inhibitors with increased potency against ROS1 and ROS1-resistance mutations, and improved intracranial activity are under evaluation in clinical trials. In this review, we discuss ROS1 rearrangements in non-small cell lung cancer, and provide an update on targeting ROS1-rearranged non-small cell lung cancer with crizotinib and newer generation tyrosine kinase inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/uso terapêutico , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Barreira Hematoencefálica/metabolismo , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Terapia de Alvo Molecular , Mutação , Permeabilidade , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética
10.
Chemosphere ; 233: 667-676, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31195271

RESUMO

In situ delivery of liquid reagents in vadose zone is limited by soil anisotropy and gravity. The enhanced delivery of persulfate (PS) as oxidant, using a new foam-based method (F-PS) was compared at bench-scale to traditional water-based (W-PS) and surfactant solution-based (S-PS) deliveries. The goal was to distribute PS uniformly in coal tar-contaminated unsaturated and anisotropic soils, both in terms of permeability and contamination. Water was the less efficiently delivered fluid because of the hydrophobicity of the contaminated soils. Surfactant enhanced PS-distribution into contaminated zones by reducing interfacial tension and inverting soil wettability. Regardless of coal tar contamination contrasts (0 vs. 5 and 1 vs. 10 g kg soil-1) or strong permeability contrasts, PS-solution injection after foam injection led to the most uniform reagents delivery. While PS-concentration varied more than 5-times between zones using W-PS and S-PS methods, it varied less than 1.6-times when the F-PS one was used. Finally, despite unfavorable conditions, the foam-based method did not show any detrimental effect regarding the oxidation of hydrocarbons compared to the W-PS and S-PS methods carried out in ideal conditions. Moreover, hydrocarbon degradation rates were slightly higher when using F-PS than S-PS due to a lower surfactant content in the targeted zone.


Assuntos
Recuperação e Remediação Ambiental/métodos , Hidrocarbonetos/análise , Poluentes do Solo/análise , Anisotropia , Alcatrão , Poluição Ambiental , Oxidantes , Oxirredução , Estresse Oxidativo , Permeabilidade , Solo/química , Tensoativos , Água
11.
Carbohydr Polym ; 219: 155-161, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31151512

RESUMO

The main objective of this study was to evaluate the changes in the characteristics of basil (Ocimum bacilicum L.) seed gum (BSG) films after modification with octenyl succinate anhydride (OSA) at different OSA:BSG weight ratios (WRs) of 0, 0.01 and 0.03. HPLC analysis revealed that the amount of added OS groups was 0%, 0.28%, and 1.01%, respectively. The introduction of OS groups along the BSG backbone was also confirmed by FT-IR and NMR analysis. XRD results revealed no significant change of physical state after modification. The contact angle (i.e., hydrophobicity) of modified BSG films was higher than that of control film. A decrease in the film solubility in water (29%) and water vapor permeability (50%), but an increase in density (14.28%) and opacity (21.37%) was observed after modification at the WR of 0.03. Also, the results showed that modification with OSA had no significant influence on the film thickness, moisture content and color properties. BSG modification with OSA at the WR of 0.03 significantly increased the flexibility and ultimate strength of respective films. The results of this study showed that OSA-modified BSG is a good candidate for developing edible films and coating with relatively high resistance to water.


Assuntos
Anidridos/química , Ocimum basilicum/química , Gomas Vegetais/química , Sementes/química , Succinatos/química , Resistência à Flexão , Interações Hidrofóbicas e Hidrofílicas , Permeabilidade , Solubilidade , Vapor , Água/química
12.
Chemosphere ; 233: 524-531, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31185336

RESUMO

Metal-organic frameworks (MOFs) addition into membranes is able to improve water flux without jeopardizing selectivity, which enhance the performance of reverse osmosis (RO) processes owing to its intrinsic physical and chemical properties, such as porosity structure and high compatibility with the polymer matrix. However, there were few studies about influences of nanoparticle size on MOFs-incorporated thin film nanocomposite (TFN) membranes. Here ZIF-8 particles with different average sizes (50, 150 and 400 nm) were synthesized and incorporated into organic monomer solution to fabricate TFN membranes for water desalination to investigate the membrane performance changed by nanomaterial size. Dispersion of ZIF-8 in selective layer during interfacial polymerization process was affected by particle size. The apparent morphology, roughness, and hydrophilicity of ZIF-8 modified TFN membranes were changed subsequently, which affected the water permeability, salt rejection and fouling resistance performance of the TFN membranes correspondingly. Our results showed that the TFN membrane comprising ZIF-8 with particle size of 50 nm had the best performance due to the highest dispersion in polyamide layer, revealing the importance of MOFs particle size in further investigation of MOFs-incorporated TFN membranes.


Assuntos
Filtração/métodos , Membranas Artificiais , Estruturas Metalorgânicas/química , Nanopartículas/química , Nylons/química , Purificação da Água/métodos , Zinco/química , Interações Hidrofóbicas e Hidrofílicas , Nanocompostos/química , Osmose , Tamanho da Partícula , Permeabilidade , Porosidade , Propriedades de Superfície
13.
J Environ Radioact ; 208-209: 105992, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31226584

RESUMO

Radon is a natural source of radioactivity and it can be found in all soils and rocks in the Earth. The presence of radon gas in indoor environments implies a serious risk for human health, already listed as carcinogenic by the World Health Organization. The most relevant methods to infer the risk for radon exposure are based on soil radon concentration and gas permeability that describe the effective radon movement in the soil. However, they neglect crucial soil properties and water content in soil, which can affect greatly soil permeability to gases. Additionally, soil permeability measurement remains expensive, difficult and time-consuming. In this paper we show a new and simple methodology to infer radon risk based on Rosetta3 pedotransfer function as well as soil texture and water content. We also determine the influence of soil texture both on the gas permeability variation in dependence on water content and on the parameter n of the van Genuchten -Mualem model, which establishes the shape of the relative permeability curves. We show that radon risk exposure may change importantly for the same soil with different soil water contents. We finally apply and validate the proposed method using radon permeability data from the Canadian component of the North American Soil Geochemical Landscapes Project (NASGLP). Results highlight that the proposed methodology provides reliable estimations of the gas permeability and reveal that the presence of water content may cross the boundary between two radon risk categories, and consequently, may change the radon risk category to safer situations.


Assuntos
Poluentes Radioativos do Ar/análise , Monitoramento de Radiação , Radônio/análise , Poluentes Radioativos do Solo/análise , Canadá , Permeabilidade , Solo/química
14.
Nat Commun ; 10(1): 2566, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31189915

RESUMO

There is clinical and scientific interest in developing local anesthetics with prolonged durations of effect from single injections. The need for such is highlighted by the current opioid epidemic. Site 1 sodium channel blockers such as tetrodotoxin (TTX) are extremely potent, and can provide very long nerve blocks but the duration is limited by the associated systemic toxicity. Here we report a system where slow release of TTX conjugated to a biocompatible and biodegradable polymer, poly(triol dicarboxylic acid)-co-poly(ethylene glycol) (TDP), is achieved by hydrolysis of ester linkages. Nerve block by the released TTX is enhanced by administration in a carrier with chemical permeation enhancer (CPE) properties. TTX release can be adjusted by tuning the hydrophilicity of the TDP polymer backbone. In vivo, 1.0-80.0 µg of TTX released from these polymers produced a range of durations of nerve block, from several hours to 3 days, with minimal systemic or local toxicity.


Assuntos
Anestésicos Locais/administração & dosagem , Portadores de Fármacos/química , Bloqueio Nervoso/métodos , Bloqueadores dos Canais de Sódio/administração & dosagem , Tetrodotoxina/administração & dosagem , Anestesia Local/métodos , Anestésicos Locais/farmacocinética , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/toxicidade , Composição de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Masculino , Camundongos , Permeabilidade , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Bloqueadores dos Canais de Sódio/farmacocinética , Tetrodotoxina/farmacocinética , Fatores de Tempo , Resultado do Tratamento
15.
Pharm Res ; 36(8): 122, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31218556

RESUMO

PURPOSE: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. METHODS: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. RESULTS: NPF had an average globule size of <75 nm. The viscosity was ~10 cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. CONCLUSION: NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces.


Assuntos
Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Nanopartículas Metálicas/química , Prata/química , Sulfadiazina/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Queimaduras/patologia , Queimaduras/fisiopatologia , Composição de Medicamentos/métodos , Quimioterapia Combinada , Emulsões , Escherichia coli/efeitos dos fármacos , Química Verde , Humanos , Masculino , Camundongos , Óleos/química , Tamanho da Partícula , Permeabilidade , Pele/efeitos dos fármacos , Pele/patologia , Pele/fisiopatologia , Staphylococcus aureus/efeitos dos fármacos , Sulfadiazina/administração & dosagem , Tensoativos/química
16.
Pharm Res ; 36(8): 124, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227928

RESUMO

PURPOSE: The aim of this work was to evaluate the use of short durations of externally applied heat with chemical penetration enhancers to improve delivery of isotretinoin to the skin and in particular via the follicular route. METHODS: A range of chemical penetration enhancers were screened for their ability to improve isotretinoin delivery into human skin with heat using infinite dose, Franz cell experiments conducted in a water bath at a higher temperature to simulate heated conditions. Following this a prototype external heating system was developed that provided short durations of heat and its ability to improve delivery of finite doses into the skin and hair follicles was assessed. RESULTS: The magnitude of the effect of heat on drug delivery was influenced by the choice of vehicle with changes in isotretinoin flux across skin ranging from not statistically significant to 25 fold increases with heat in the infinite dose studies. The prototype heating system provided significant increases in the total delivery of isotretinoin into the skin from an optimised vehicle. Drug distribution in the skin revealed significant increases in isotretinoin delivery to the hair follicles, and deeper skin layers, but not to the stratum corneum, providing strong evidence that the enhancement in delivery occurred mainly via the hair follicles. CONCLUSION: These data indicate that the use of short durations of heat combined with chemical penetration enhancers offers a valuable strategy for improving the delivery of drugs such as isotretinoin to the skin via the hair follicles. Graphical Abstract Schematic illustration of the sodium thiosulphate heating system on a Franz diffusion cell and the subsequent impact of a short burst of heat on the delivery of isotretinoin into human skin.


Assuntos
Fármacos Dermatológicos/farmacologia , Portadores de Fármacos/química , Folículo Piloso/química , Isotretinoína/farmacologia , Administração Cutânea , Fármacos Dermatológicos/administração & dosagem , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Folículo Piloso/citologia , Temperatura Alta , Humanos , Isotretinoína/administração & dosagem , Permeabilidade , Pele/metabolismo , Absorção Cutânea , Tiossulfatos/química
17.
J Environ Radioact ; 207: 27-36, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31154122

RESUMO

A series of large-scale experimental tests were performed to examine the flow behaviour of the T1 Struc and T2 Perm specified granular fill materials with active and passive depressurisations. Granular materials were compacted and tested at various compacted thicknesses. Compaction works were performed using a field compactor and compaction degrees of the materials were found to be higher than those induced by a standardised small-scale compactor. The air permeability (kah) values of the materials were obtained with active depressurisation. It was found that the overall trend of kah tended to decrease with the increase in the compacted thickness of the materials and were found to be compatible with those determined by the small-scale test apparatus. Results from passive depressurisation tests indicated that the rotating cowls performed the best, followed by a static open pipe and a pipe with a cap.


Assuntos
Radônio/análise , Poluentes Radioativos do Solo/análise , Solo/química , Permeabilidade , Radônio/química , Poluentes Radioativos do Solo/química
18.
BMC Complement Altern Med ; 19(1): 129, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196040

RESUMO

BACKGROUND: Green tea has polyphenols like flavonoids and catechins; mainly epigallocatechin-3-gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC) and epicatechin (EC), out of which EGCG is of higher abundance. EGCG has shown preventive role in hypercholesterolemia. However, due to low oral bioavailability, a need arises to improve its membrane permeability and transporter-mediated intestinal efflux. Therefore, an attempt was made to enhance permeability and bioavailability of EGCG using curcumin to treat hyperlipidemia. Further, it was formulated in herbal tea bags to achieve patient compliance. METHODS: EGCG extracted from green tea leaves was confirmed by High Performance Thin Layer Chromatography. Green tea extract (GTE), curcumin and their mixtures were subjected to Fourier Transform Infra-Red spectroscopy and Differential Scanning Calorimetry for compatibility studies. Powder formulation was prepared comprising GTE, curcumin, sucralose and cardamom. RESULTS: Ex-vivo study was performed on everted goat intestine, analyzed by HPLC and demonstrated highest permeation of GTE:curcumin (220:50) (53.15%) than GTE (20.57%). Antihyperlipidemic activity was performed in rats for 15 days. Blood sample analysis of rats of test groups (formulation and GTE solution) fed on high fat diet showed (mg/dl):cholesterol 80 and 90, triglycerides 73.25 and 85.5, HDL 50.75 and 46, LDL 43.9 and 46, VLDL 14.65 and 17.1 respectively with significant lipid regulating effect. CONCLUSION: Curcumin enhanced permeability of EGCG. Therefore, P-glycoprotein pump inside intestine can be potential mechanism to enhance permeability of EGCG. Thus, EGCG-curcumin herbal tea bag is promising nutraceutical to treat hyperlipidemia in day-to-day life achieving patient compliance.


Assuntos
Antioxidantes/farmacocinética , Catequina/análogos & derivados , Curcumina/administração & dosagem , Hiperlipidemias/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Disponibilidade Biológica , Catequina/administração & dosagem , Catequina/farmacocinética , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Masculino , Permeabilidade , Fitoterapia , Ratos Sprague-Dawley , Chá
19.
Int J Nanomedicine ; 14: 3439-3454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190802

RESUMO

Objective: The microbial, physico-chemical and optical corruptions threaten a variety of foods and drugs and consequently the human biological safety and its accessible resources. The humanbeing's tendency towards bio-based materials and natural plant-extracts led to an increase in the usage of antimicrobial biocomposites based on medicinal herbs. Miswak (Salvadora persica L.) extract (SPE) has been proved effective for its antimicrobial and other biological activities. Therefore, in this study, titanium dioxide (TiO2) nanoparticles (TONP) and SPE were applied to fabricate antimicrobial carboxymethyl cellulose (Na-CMC) based bio-nanocomposites which would simultaneously promote some thermo-physical and barrier properties. Methods: CMC-neat film (C1), CMC/TONP-2% (C2) and CMC/TONP-2% with 150, 300 and 450 mg/mL SPE (SPE150, SPE30 and SPE450, respectively) were fabricated. The physical and mechanical properties; elemental mapping analysis (MAP), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA-DTG); fourier transform infrared (FTIR), energy-dispersive X-ray (EDX) and UV-vis spectroscopies were done to further validate the results. Results: Addition of TONP (2%) improved the blocking of UV light at 280 nm while SPE-containing nanocomposites completely blocked it. FTIR, XRD and SEM confirmed the formation of homogeneous films and high miscibility of applied materials. TONP led to an increase in Young's modulus (YM) and stress at break (SB) while SPE decreased them and enhanced the elongation to break (EB) (flexibility) of the active nanocomposites. Compared to CMC-film, the thermo-gravimetric analysis (TGA-DTG) showed a higher thermal stability for CMC/TONP and CMC/TONP/SPE nanocomposites. The EDX spectroscopy and elemental mapping analysis (MAP) proved the existence and well-distributedness of Na, K, Cl, S, Ti, F and N elements in SPE-activated nanocomposites. The pure SPE and SPE-activated nanocomposites showed a favorable antimicrobial activity against both gram-positive (Staphylococcus aureus) and negative (Escherichia coli) bacteria. Conclusion: The CMC-TiO2-SPE nanocomposites were homogeneously produced. Combination of TiO2 nanoparticles and dose-dependent SPE led to an improvement of thermal stability, and high potential in antimicrobial and UV-barrier properties. These results can generally highlight the role of the fabricated antimicrobial bio-nanocomposites as a based for different applications especially in food/drug packaging or coating.


Assuntos
Antibacterianos/farmacologia , Nanocompostos/química , Nanopartículas/química , Extratos Vegetais/farmacologia , Salvadoraceae/química , Temperatura Ambiente , Titânio/química , Elementos , Humanos , Umidade , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Permeabilidade , Espectrofotometria Ultravioleta , Staphylococcus aureus/efeitos dos fármacos , Vapor , Termogravimetria , Difração de Raios X
20.
Int J Nanomedicine ; 14: 3601-3613, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190814

RESUMO

Introduction: Kolliphor® EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity. Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor® HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Emulsões/química , Nanopartículas/química , Mucosa Nasal/fisiologia , Polietilenoglicóis/química , Animais , Neoplasias Encefálicas/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Concentração Inibidora 50 , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Permeabilidade , Anidridos Ftálicos/química , Ratos Endogâmicos F344 , Solubilidade , Tensoativos/química , Análise de Sobrevida , Carga Tumoral , Viscosidade
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