Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nanomaterials (Basel) ; 12(4)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35215013

RESUMO

Nanoparticles are widely used for biomedical applications such as vaccine, drug delivery, diagnostics, and therapeutics. This study aims to reveal the influence of nanoparticle surface functionalization on protein corona formation from blood serum and plasma and the subsequent effects on the innate immune cellular responses. To achieve this goal, the surface chemistry of silica nanoparticles of 20 nm diameter was tailored via plasma polymerization with amine, carboxylic acid, oxazolines, and alkane functionalities. The results of this study show significant surface chemistry-induced differences in protein corona composition, which reflect in the subsequent inflammatory consequences. Nanoparticles rich with carboxylic acid surface functionalities increased the production of pro-inflammatory cytokines in response to higher level of complement proteins and decreased the number of lipoproteins found in their protein coronas. On another hand, amine rich coatings led to increased expressions of anti-inflammatory markers such as arginase. The findings demonstrate the potential to direct physiological responses to nanomaterials via tailoring their surface chemical composition.

2.
Int J Pharm ; 614: 121446, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34998923

RESUMO

The influence of amino acids, other than leucine, in improving aerosolization of inhalable powders has not been widely explored. This detailed study focused on the use of methionine, another promising endogenous amino acid, in high dose spray-dried co-amorphous powders by investigating the influence of methionine proportion (0 - 20% w/w), and feed concentration (0.2 - 0.8% w/v) on aerosolization of kanamycin, a model drug, using a design of experiment approach. Low frequency Raman spectroscopy was used to assess the stability of the powders stored at 25 °C/53% relative humidity over 28 days. An increase in concentration of methionine was associated with an increase in fine particle fraction (FPF), with the highest FPF of 84% being achieved at 20% w/w and 0.2% w/v feed concentration. With an increase in feed concentration, both yield and particle size increased for all formulations; the FPF did not change except for kanamycin only formulation in which it decreased. During storage at high humidity, similar aerosolization stabilities were offered by different proportions of methionine although methionine crystallized out in all formulations. Furthermore, the crystallization was accompanied by surface enrichment of methionine on the particles. This study suggests that there is a direct relationship between methionine content and aerosolization for kanamycin-methionine amorphous matrices but feed concentration has little effect. In addition, methionine proportion has no effect on physical stability of such matrices at high humidity.


Assuntos
Inaladores de Pó Seco , Metionina , Administração por Inalação , Aerossóis , Tamanho da Partícula , Pós , Análise Espectral Raman
3.
Pharmaceutics ; 13(7)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34371765

RESUMO

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs.

4.
Biointerphases ; 15(5): 051005, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972145

RESUMO

Plasma polymers derived from oxazoline precursors present a range of versatile properties that is fueling their use as biomaterials. However, coatings deposited from commonly used methyl and ethyl oxazoline precursors can be sensitive to the plasma deposition conditions. In this work, we used various spectroscopic methods (ellipsometry, x-ray photoelectron spectroscopy, and time of flight secondary ion mass spectrometry) and cell viability assays to evaluate the transferability of deposition conditions from the original plasma reactor developed by Griesser to a new wider, reactor designed for upscaled biosensors applications. The physicochemical properties, reactivity, and biocompatibility of films deposited from 2-isopropenyl-2-oxazoline were investigated. Thanks to the availability of an unsaturated pendant group, the coatings obtained from this oxazoline precursor are more stable and reproducible over a range of deposition conditions while retaining reactivity toward ligands and biomolecules. This study identified films deposited at 20 W and 0.012 mbar working pressure as being the best suited for biosensor applications.


Assuntos
Técnicas Biossensoriais/métodos , Nanoestruturas/química , Oxazóis/química , Gases em Plasma/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Análise de Componente Principal
5.
Biointerphases ; 15(3): 031015, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32590900

RESUMO

The stable nitroxide radical TEMPO [(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl] has a multitude of applications in fields ranging from energy storage to biomedical applications and many more. However, to date, the processes of incorporating nitroxide radicals into thin-film coatings are laborious and not cost-effective, which hinders their wider use in many applications. In contrast, the authors have recently demonstrated the facile method of plasma polymerization of TEMPO into thin-film coatings that retain the stable nitroxide radicals. In this work, we are using three types of mass spectroscopic methods (plasma-mass spectrometry, time of flight secondary ion mass spectrometry, and high-performance liquid chromatography-mass spectrometry) and electron spin resonance to track the fate of the TEMPO molecule from monomer flask through the plasma and inside the resulting coatings. The results of this study demonstrate that TEMPO is a versatile monomer that can be used across different plasma reactors and reliably retain the stable nitroxide radical in the resulting thin-film coatings if certain process conditions are observed, namely, higher process pressures and lower powers.


Assuntos
Óxidos N-Cíclicos/química , Óxidos de Nitrogênio/química , Gases em Plasma/química , Polimerização , Espectroscopia de Ressonância de Spin Eletrônica , Íons , Análise de Componente Principal
6.
Adv Healthc Mater ; 8(17): e1900595, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31328896

RESUMO

This report addresses the issue of optimizing extracellular matrix protein density required to support osteogenic lineage differentiation of mesenchymal stem cells (MSCs) by culturing MSCs on surface-bound density gradients of immobilized collagen type I (COL1) and osteopontin (OPN). A chemical surface gradient is prepared by tailoring the surface chemical composition from high hydroxyl groups to aldehyde groups using a diffusion-controlled plasma polymerization technique. Osteogenesis on the gradient surface is determined by immunofluorescence staining against Runx2 as an early marker and by staining of calcium phosphate deposits as a late stage differentiation marker. The Runx2 intensity and calcified area increase with increasing COL1 density up to a critical value corresponding to 124.2 ng cm-2 , above which cell attachment and differentiation do not rise further, while this critical value for OPN is 19.0 ng cm-2 . This gradient approach may facilitate the screening of an optimal biomolecule surface density on tissue-engineered scaffolds, implants, or tissue culture ware to obtain the desired cell response, and may generate opportunities for more cost-effective regenerative medicine.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Proteínas da Matriz Extracelular/farmacologia , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Aldeídos/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Etanol/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteopontina/farmacologia , Ratos Wistar
7.
Int J Pharm ; 568: 118504, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31299339

RESUMO

Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or l-leucine]. The co-jet-milled formulations were characterized for particle size, morphology, cohesion, Carr's index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, the ciprofloxacin co-jet-milled with l-leucine at >0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5% w/w for both MgSt and l-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and l-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while l-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and l-leucine surface coverages on aerosolization and powder flow properties of inhalation particles.


Assuntos
Antibacterianos/química , Ciprofloxacina/química , Inaladores de Pó Seco , Leucina/química , Lubrificantes/química , Ácidos Esteáricos/química , Aerossóis , Composição de Medicamentos , Liberação Controlada de Fármacos , Excipientes/química , Tamanho da Partícula , Pós , Propriedades de Superfície
8.
J Pharm Sci ; 108(9): 3146-3151, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31112716

RESUMO

Homogeneous mixing of 2 cohesive jet-milled drug powders is a challenge for pharmaceutical manufacturing on account of their cohesive nature resulting in the formation of strong and random agglomerates. In this study, colistin and ciprofloxacin were co-jet milled to develop combinational antibiotic dry powder formulations for inhalation. The properties of particle size, morphology, content uniformity, and in vitro aerosolization were evaluated. The distribution of 2 drugs in the co-jet milled powders was assessed using time-of-flight-secondary ion mass spectrometry. The co-jet milled powders demonstrated an acceptable content uniformity indicating homogeneity. In general, time-of-flight-secondary ion mass spectrometry images showed relatively homogeneous distributions of ciprofloxacin and colistin in the co-milled formulations. Importantly, the 2 drugs generally had the similar fine particle fraction and deposition behavior in each combinational formulation supporting that the particle mixtures were relatively homogenous and could maximize the antimicrobial synergy. In conclusion, co-jet milling could be a viable technique to produce the combination powders for inhalation.


Assuntos
Antibacterianos/química , Química Farmacêutica , Ciprofloxacina/química , Colistina/química , Composição de Medicamentos/métodos , Administração por Inalação , Aerossóis , Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Colistina/administração & dosagem , Combinação de Medicamentos , Inaladores de Pó Seco , Estudos de Viabilidade , Tamanho da Partícula , Pós
9.
Chem Commun (Camb) ; 55(2): 171-174, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30418438

RESUMO

Microneedle patches have become an exciting means for transdermal delivery of various therapeutics. Herein, we report on self-sterilizing dissolving nanosilver-loaded microneedle patches created from carboxymethylcellulose capable of suppressing microbial pathogen growth at the insertion site.

10.
Mol Pharm ; 15(9): 4004-4020, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30028947

RESUMO

This study aimed to develop dry powder inhaler (DPI) combination formulations of ciprofloxacin and colistin for use in respiratory infections. Effects of colistin on physical stability and aerosolization of spray-dried ciprofloxacin were examined. The combination DPI formulations were produced by co-spray drying colistin and ciprofloxacin in mass ratios of 1:1, 1:3, and 1:9. Colistin and ciprofloxacin were also co-sprayed with l-leucine in the mass ratio of 1:1:1. The physical and aerosolization stability of the selected co-sprayed formulations stored at 20, 55, and 75% relative humidity (RH) were examined. Formulation characterizations were carried out using powder X-ray diffraction (PXRD) for crystallinity, scanning electron microscopy for morphology and particle size distribution, and dynamic vapor sorption for moisture sorption. Particle surface analysis was performed using X-ray photoelectron spectroscopy, energy dispersive X-ray spectrometry, and nano-time-of-flight secondary ion mass spectrometry. Potential intermolecular interactions were studied using Fourier-transform infrared spectroscopy (FTIR). Aerosol performance was evaluated using a multistage liquid impinger with a RS01 monodose inhaler device. PXRD diffractograms showed that the co-spray-dried colistin-ciprofloxacin formulation in the mass ratio (1:1) was amorphous at 55% RH for up to 60 days; whereas the co-spray-dried colistin-ciprofloxacin (1:3) and colistin-ciprofloxacin (1:9) crystallized after storage for 3 days at 55% RH. However, the extent of crystallization for the combination formulations was less as compared to the spray-dried ciprofloxacin alone formulation. Surface morphology of the co-spray-dried formulations at different concentrations did not change even after storage at 55% RH for 60 days, unlike the spray-dried ciprofloxacin alone powder which became rougher after 3 days of storage at 55% RH. Surface analysis data indicated surface enrichment of colistin in the co-spray-dried formulations. Increasing colistin concentration on the composite particles surfaces improved aerosol performance of ciprofloxacin. FTIR data demonstrated intermolecular interactions between colistin and ciprofloxacin, thereby delaying and/or preventing crystallization of ciprofloxacin when co-spray-dried. Co-spray drying ciprofloxacin with colistin in the mass ratio (1:1) completely prevented crystallization of ciprofloxacin at 55% RH for up to 60 days. However, the colistin-ciprofloxacin formulation (1:1) began to fuse when stored at 75% RH due to moisture absorption resulting in a compromised aerosol performance. In contrast, the colistin-ciprofloxacin-leucine (1:1:1) formulation demonstrated no particle fusion, enabling a stable aerosol performance at 75% RH for 7 days. This study demonstrated that incorporation of colistin in the spray-dried formulations can improve physical stability and aerosolization of amorphous ciprofloxacin at 55% RH. At 75% RH, further addition of l-leucine in the formulation prevented particle fusion and deterioration in aerosol performance, attributed to the enrichment of nonhygroscopic l-leucine on the particle surface.


Assuntos
Aerossóis/química , Ciprofloxacina/química , Colistina/química , Administração por Inalação , Estabilidade de Medicamentos , Sinergismo Farmacológico , Inaladores de Pó Seco , Excipientes/química , Leucina/química , Tamanho da Partícula , Difração de Raios X
11.
Macromol Rapid Commun ; 39(19): e1800178, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29748983

RESUMO

The development of enzyme-responsive hyaluronic acid methacrylate (HYAMA)-coated porous silicon (pSi) films and their application in electrochemical diagnostic devices for the in situ detection of the enzyme hyaluronidase (hyal), which is secreted by Staphylococcus aureus (S. aureus) bacteria, are reported. The approach relies on a HYAMA-pSi electrode made of thermally hydrocarbonized pSi (pSi-THC) that is impregnated with crosslinked HYAMA/polyethylene glycol diacrylate (PEGDA) hydrogels. The enzymatic degradation of HYAMA by bacterial hyal is monitored by differential pulse voltammetry (DPV) utilizing pSi-THC as a working electrode and ferro/ferricyanide (FF) as external redox probe. The degradation of HYAMA results in reduced diffusion of the redox probe through the partially charged film, thereby enabling the detection of hyal by DPV. In addition to the determination of the concentration-dependent response in NaOAc buffer (pH 5.2), the detection of hyal as indicator for the presence of S. aureus bacteria above a threshold level in bacterial supernatants and artificial wound fluid is highlighted.


Assuntos
Proteínas de Bactérias/análise , Técnicas Eletroquímicas , Ácido Hialurônico/química , Hialuronoglucosaminidase/análise , Membranas Artificiais , Silício/química , Staphylococcus aureus/enzimologia
12.
Environ Pollut ; 240: 725-732, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29778058

RESUMO

Oil pollution of waters is one of the most serious environmental problems globally. The long half-life and persistence within the environment makes oil particularly toxic and difficult to remediate. There is a significant need for efficient and cost-effective oil recovery technologies to be brought in to practice. In this study, we developed a facile and efficient magnetic separation method. The surface of 316L stainless steel nanoparticles was modified by plasma deposition of 1,7-octadiene and perfluorooctane, producing relatively hydrophobic coatings having water contact angles of 86 and 100°, respectively. Both coatings had high oil removal efficiency (ORE) of >99%. The captured oil could be easily separated by applying an external magnetic force. The ease of material preparation and separation from the water after the oil is captured, and its high ORE is a compelling argument for further development and optimization of the technology to possible utilization into practice. Furthermore, the capacity of plasma polymerization to deliver desired surface properties can extend the application of the technology to removing other chemical and biological contaminants from polluted waters.


Assuntos
Recuperação e Remediação Ambiental/métodos , Óleos/análise , Poluição por Petróleo/análise , Poluição da Água/análise , Purificação da Água/métodos , Alcenos/química , Fluorocarbonos/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/química , Polímeros/química , Aço Inoxidável/química , Propriedades de Superfície
13.
Eur J Pharm Sci ; 118: 216-226, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29625212

RESUMO

This study aimed to develop a high payload dry powder inhalation formulation containing a combination of the first line anti-tubercular drug, pyrazinamide, and the second line drug, moxifloxacin HCl. Individual powders of pyrazinamide (PSD) and moxifloxacin (MSD) and combination powders of the two drugs without (PM) and with 10% l-leucine (PML) and 10% DPPC (PMLD) were produced by spray drying. PSD contained >10 µm crystalline particles and showed poor aerosolization behaviour with a fine particle fraction (FPF) of 18.7 ±â€¯3.4%. PM produced spherical hollow particles with aerodynamic diameter < 5 µm and PML showed improved aerosolization with a high FPF of ~70%. However, PMLD showed a significantly reduced FPF (p > 0.05) compared to PML. Solid state studies and surface elemental analysis by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the surface coating of particles contained amorphous moxifloxacin and both l-leucine and DPPC over crystalline pyrazinamide. Furthermore, pyrazinamide, moxifloxacin, PML and PMLD were found to display low toxicity to both A549 and Calu-3 cell lines even at a concentration of 100 µg/mL. In conclusion, a combination powder formulation of PML has the potential to deliver a high drug dose to the site of infection resulting in efficient treatment.


Assuntos
Antituberculosos/administração & dosagem , Fluoroquinolonas/administração & dosagem , Pirazinamida/administração & dosagem , Aerossóis , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Combinação de Medicamentos , Estabilidade de Medicamentos , Humanos , Moxifloxacina , Pós , Tuberculose Pulmonar/tratamento farmacológico
14.
Mol Pharm ; 15(5): 2045-2053, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29641898

RESUMO

Surface composition critically impacts stability (e.g., crystallization) and performance (e.g., dissolution) of spray dried amorphous solid dispersion (ASD) formulations; however, traditional characterization techniques such as Raman and infrared spectroscopies may not provide useful information on surface composition on the spray dried ASD particles due to low spatial resolution, high probing depth, and lack of quantitative information. This study presents an advanced surface characterization platform consisting of two complementary techniques: X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Such a platform enables qualitative and quantitative measurements of surface composition for the fine spray dried ASD particles with ultrasurface-sensitivity (less than 10 nm from the surface) and superior spatial resolution (approximately 250 nm for ToF-SIMS). Both XPS and ToF-SIMS demonstrated that the polymer (PVPVA) was dominantly enriched on the surface of our spray dried naproxen-PVPVA ASD particles. Of a particular note was that XPS could differentiate two batches of spray dried ASD particles with a subtle difference in surface composition produced by varying feed solution solvents. This advanced surface characterization platform will provide essential surface information to understand the mechanisms underlying the impact of surface composition on stability (e.g., crystallization) and functionality (e.g., dissolution) in future studies.


Assuntos
Naproxeno/química , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Espectrometria de Massas/métodos , Espectroscopia Fotoeletrônica/métodos , Polímeros/química , Povidona/análogos & derivados , Povidona/química , Solubilidade/efeitos dos fármacos , Solventes/química , Propriedades de Superfície
15.
Int J Pharm ; 542(1-2): 72-81, 2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29524618

RESUMO

Pharmacotherapy of tuberculosis is potentially more efficient when delivered by the inhaled route than by the current oral and/or parenteral routes due to the higher concentration of drug reaching the primary region of infection in the lungs. This study investigated the influence of the amino acid l-leucine alone and in combination with the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), on the aerosolization behaviour of the anti-TB drugs, pyrazinamide and moxifloxacin HCl. Spray dried powders of pyrazinamide (P), moxifloxacin (M) alone and in combination with 10% l-leucine (PL and ML) and 10% DPPC (PLD and MLD) were produced. The particle sizes of all powders except P were in the inhalable size range (<5 µm) but differ in their morphology in presence of the excipients. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed the migration of surface active l-leucine and DPPC onto the surface of the particles during the spray drying process. The aerosolization from a dry powder inhaler, Aerolizer®, using a Next Generation Impactor revealed fine particle fraction (FPF) values for P, PL and PLD of 18.7 ±â€¯3.4%, 53.0 ±â€¯3.2% and 74.5 ±â€¯5.3% respectively while FPF values for M, ML and MLD were 55.6 ±â€¯3.3%, 74.7 ±â€¯4.7% and 74.1 ±â€¯1.3% respectively. In conclusion, the differences in the aerosolization behaviours of the pyrazinamide and moxifloxacin spray dried powders with and without excipients was a combination of difference in the surface morphology and surface composition.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Antituberculosos/química , Fluoroquinolonas/química , Leucina/química , Pirazinamida/química , Aerossóis , Química Farmacêutica , Dessecação , Excipientes/química , Moxifloxacina , Tamanho da Partícula , Pós
17.
Int J Pharm ; 541(1-2): 11-18, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29454904

RESUMO

Amorphous powders are thermodynamically unstable, significantly impacting the processing, storage and performance of a product. Therefore, stabilization of the amorphous contents is in demand. In this study, disodium cromoglycate (DSCG) powder was chosen as a model drug because it is amorphous and highly hygroscopic after spray drying. Sodium stearate (NaSt) was co-spray dried with DSCG at various concentrations (10, 50 and 90% w/w) to investigate its effect against moisture-induced deterioration on the in vitro aerosolization performance of DSCG. Particle size distribution and morphology were measured by laser diffraction and scanning electron microscopy (SEM). Physicochemical properties of the powders were analysed by X-ray powder diffraction (XRPD) and dynamic vapour sorption (DVS). Particle surface chemistry was analysed by the time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro dissolution behaviours of the spray-dried (SD) powders were tested by the Franz cell apparatus. In vitro aerosolization performance of SD formulations stored at different relative humidity (RH) was evaluated by a multi-stage liquid impinger (MSLI), using an Osmohaler® at 100 L/min. Results showed that adding NaSt in the formulation not only increased the aerosolization performance of DSCG significantly, but also effectively reduced the deleterious impact of moisture. No significant difference was found in the fine particle fraction (FPF) of formulations containing NaSt before and after storage at both 60% and 75% RH for one week. However, after one month storage at 75% RH, SD formulation containing 10% NaSt showed a reduction in FPF, while formulations containing 50% or 90% NaSt showed no change. The underlying mechanism was that NaSt increased the crystallinity of the powders and its presence on the particle surface reduced particle aggregations and cohesiveness. However, NaSt at high concentration could reduce dissolution rate, which needs to be taken into consideration.


Assuntos
Cromolina Sódica/química , Dessecação/métodos , Ácidos Esteáricos/química , Molhabilidade , Administração por Inalação , Aerossóis , Química Farmacêutica , Cromolina Sódica/farmacocinética , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Excipientes/química , Umidade/efeitos adversos , Tamanho da Partícula , Pós
18.
Pharm Res ; 35(2): 28, 2018 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-29374368

RESUMO

PURPOSE: Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution. METHODS: The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated. RESULTS: The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations. CONCLUSIONS: We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Infecções Respiratórias/tratamento farmacológico , Administração por Inalação , Antibacterianos/farmacocinética , Azitromicina/farmacocinética , Composição de Medicamentos/métodos , Inaladores de Pó Seco , Humanos , Leucina/química , Tamanho da Partícula , Solubilidade
19.
Adv Sci (Weinh) ; 3(6): 1500383, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27812471

RESUMO

Bacterial wound infections can cause septicemia and lead to limb amputation or death. Therefore, early detection of bacteria is important in chronic wound management. Here, an optical biosensor based on porous silicon resonant microcavity (pSiRM) structure modified with fluorogenic peptide substrate is demonstrated to detect the presence of Sortase A (SrtA), a bacterial enzyme found in the cell membrane protein of Staphylococcus aureus. The combination of fluorescence enhancement effects of the pSiRM architecture with the incorporation of SrtA fluorogenic peptide substrate within the pSi matrix enables the sensing of SrtA with an outstanding limit of detection of 8 × 10-14 m. Modification of the pSiRM structure with microscale spots of two fluorogenic peptide substrates, one specific for SrtA and the other for matrix metalloproteinases, effectively demonstrates the feasibility to perform multiplexed biomarker analysis. The results in this study highlight the potential of the pSiRM sensing platform as a point-of-care diagnostic tool for biomarkers of bacterial wound infection.

20.
ACS Appl Mater Interfaces ; 8(10): 6354-62, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26901823

RESUMO

Infections caused by the bacterial colonization of medical devices are a substantial problem to patients and healthcare. Biopassive polyoxazoline coatings are attracting attention in the biomedical field as one of the potential solutions to this problem. Here, we present an original and swift way to produce plasma-deposited oxazoline-based films for antifouling applications. The films developed via the plasma deposition of 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline have tunable thickness and surface properties. Diverse film chemistries were achieved by tuning and optimizing the deposition conditions. Human-derived fibroblasts were used to confirm the biocompatibility of oxazoline derived coatings. The capacity of the coatings to resist biofilm attachment was studied as a function of deposition power and mode (i.e., continuous wave or pulsed) and precursor flow rates for both 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline. After careful tuning of the deposition parameters films having the capacity to resist biofilm formation by more than 90% were achieved. The substrate-independent and customizable properties of the new generation of plasma deposited oxazoline thin films developed in this work make them attractive candidates for the coating of medical devices and other applications where bacteria surface colonization and biofilm formation is an issue.


Assuntos
Biofilmes/crescimento & desenvolvimento , Fibroblastos/metabolismo , Membranas Artificiais , Oxazóis/química , Staphylococcus epidermidis/fisiologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...