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1.
Pharm Res ; 29(9): 2445-55, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22584947

RESUMEN

PURPOSE: To study the effect of the size of the surface-coated polycaprolactone (PCL) microparticle carriers on the aerosolization and dispersion of Salbutamol Sulfate (SS) from Dry Powder Inhaler (DPI) formulations. METHODS: The microparticles were fabricated using an emulsion technique in four different sizes (25, 48, 104 and 150 µm) and later coated with Magnesium stearate (MgSt) and leucine. They were characterized by laser diffraction and SEM. The Fine Particle Fraction (FPF) of SS from powder mixtures was determined by a Twin Stage Impinger (TSI). RESULTS: As the carrier size increased from 25 µm to 150 µm, the FPF of the SS delivered by the coated PCL particles increased approximately four fold. A linear relationship was found between the FPF and Volume mean Diameter (VMD) of the particles over this range. CONCLUSIONS: The dispersion behaviour of SS from PCL carriers was dependent on the inherent size of the carriers and the increased FPF of SS with increased carrier size probably reflects the higher mechanical forces produced due to the carrier-carrier collisions or collisions between the carrier particles and the internal walls of the inhaler during aerosolization.


Asunto(s)
Albuterol/administración & dosificación , Broncodilatadores/química , Inhaladores de Polvo Seco , Microesferas , Poliésteres/química , Portadores de Fármacos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Poliésteres/administración & dosificación
2.
Biomaterials ; 29(12): 1785-95, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18241915

RESUMEN

Chronic ulcers are an important and costly medical issue, imposing considerable pain, reduced mobility and decreased quality of life. The common pathology in these chronic wounds is excessive proteolytic activity, resulting in degradation of key factors critical to the ulcer's ability to heal. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, have been shown to have increased activity in chronic wound fluid (CWF), with many authors suggesting that they need to be inhibited for the ulcer to heal. The studies we report here show that the excessive MMP activity in CWF can be inhibited with the bisphosphonate alendronate, in the form of a sodium salt, a functionalised analogue, and tethered to a poly(2-hydroxy methacrylate) (PHEMA) hydrogel. Furthermore, these functionalised alendronate hydrogels appear to be biologically inert as assessed in a three-dimensional ex vivo human skin equivalent model. Together, these results highlight the potential use of a tethered MMP inhibitor to inhibit protease activity in wound fluid. This approach may improve wound healing as it still allows MMPs to remain active in the upper cellular layers of the ulcer bed where they perform vital roles in wound healing; thus may offer an attractive new device-orientated wound therapy.


Asunto(s)
Líquidos Corporales/metabolismo , Difosfonatos/administración & dosificación , Portadores de Fármacos/química , Hidrogeles/química , Inhibidores de la Metaloproteinasa de la Matriz , Úlcera/tratamiento farmacológico , Úlcera/enzimología , Cicatrización de Heridas/efectos de los fármacos , Difosfonatos/química , Activación Enzimática/efectos de los fármacos , Humanos , Ensayo de Materiales
3.
J Nanosci Nanotechnol ; 7(10): 3477-86, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18330161

RESUMEN

Raw and purified samples of carbon nanotubes are considered as multicomponent systems with a distribution of carbonaceous, amorphous, multishell graphitic particles and nanotubes, together with the particles of metal compounds from the catalyst. With respect to the carbon nanotube fractions, a distribution of size, defect concentrations, and functionalities needs to be taken into account. In order to address the problem of quantitative evaluation of purity it is necessary to measure the quality and distribution of the carbon nanotubes. In this research conventional and high resolution thermogravimetry are applied to quantify different fractions of carbonaceous and metallic materials in raw and moderately purified single walled and multiwalled carbon nanotubes. For each oxidized fraction, defined by careful line shape analysis of the derivative thermogravimetric curves (DTG), the temperature of maximum rate of oxidation, the temperature range for this oxidation, related to the degree of homogeneity, and the amount of associated material is specified. The attribution of carbonaceous materials to each fraction in the distribution was based on SEM and TEM measurements and the literature. The MWNT purified sample with 1.6 wt% metal oxide was investigated by high resolution thermogravimetry (HRTG). The quantitative assessment for the carbonaceous fractions was 25 wt% of amorphous and high defect carbonaceous materials including nanotubes, 54 wt% MWNT and 20 wt% multishell graphitic particles. A qualitative evaluation of these fractions was obtained from the SEM and TEM images and supports these results. The accuracy of the values, taking into account other measurements performed on the same batch of material, should be more sensible than +/-4 wt%.


Asunto(s)
Cristalización/métodos , Ensayo de Materiales/métodos , Microscopía Electrónica de Rastreo/métodos , Microscopía Electrónica de Transmisión/métodos , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestructura , Termogravimetría/métodos , Sustancias Macromoleculares/química , Conformación Molecular , Nanotecnología/métodos , Tamaño de la Partícula , Propiedades de Superficie
4.
J Pharm Sci ; 101(2): 733-45, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21956254

RESUMEN

This study reports the factors controlling aerosolization of salbutamol sulfate (SS) from mixtures with polycaprolactone (PCL) microspheres fabricated using an emulsion technique with polyvinyl alcohol (PVA) as stabilizer. The fine particle fraction (FPF) of SS from PCL measured by a twin-stage impinger was unexpectedly found to be zero, although scanning electron microscopy showed that the drug coated the entire microsphere. Precoating the microspheres with magnesium stearate (MgSt) excipient solutions (1%-2%) significantly increased (p < 0.05, n = 5) the FPF of SS (11.4%-15.4%), whereas precoating with leucine had a similar effect (FPF = 11.3 ± 1.1%), but was independent of the solution concentration. The force of adhesion (by atomic force microscopy) between the PCL microspheres and SS was reduced from 301.4 ± 21.7 nN to 110.9 ± 30.5 nN and 121.8 ± 24.6 nN, (p < 0.05, n = 5) for 1% and 2% MgSt solutions, respectively, and to 148.1 ± 21.0 nN when coated with leucine. The presence of PVA on the PCL microspheres (detected by X-ray photoelectron spectroscopy) affected the detachment of SS due to strong adhesion between the two, presumably due to capillary forces acting between them. Precoating the microspheres with excipients increased the FPF significantly by reducing the drug-carrier adhesion.


Asunto(s)
Aerosoles , Albuterol/administración & dosificación , Broncodilatadores/administración & dosificación , Inhaladores de Polvo Seco , Microesferas , Poliésteres/química , Cromatografía Líquida de Alta Presión , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Espectrometría por Rayos X
5.
J Biomed Mater Res A ; 100(7): 1919-27, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22581620

RESUMEN

This study investigates the effect of well-defined poly(dimethylsiloxane)-poly(ethylene glycol) (PDMS-PEG) ABA linear block co-oligomers on the proliferation of human dermal fibroblasts. The co-oligomers assessed ranged in molecular weight (MW) from 1335 to 5208 Da and hydrophilic-lipophilic balance (HLB) from 5.9 to 16.6 by varying the number of both PDMS and PEG units. In general, it was found that co-oligomers of low MW or intermediate hydrophilicity significantly reduced fibroblast proliferation. A linear relationship between down-regulation of fibroblast proliferation, and the ratio HLB/MW was observed at concentrations of 0.1 and 1.0 wt % of the oligomers. This enabled the structures with highest efficiency to be determined. These results suggest the possible use of the PEG-PDMS-PEG block co-oligomers as an alternative to silicone gels for hypertrophic scar remediation.


Asunto(s)
Siloxanos/farmacología , Piel/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Humanos , Siloxanos/química , Piel/citología
6.
J Biomed Mater Res A ; 95(2): 620-31, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20725963

RESUMEN

The formation of hypertrophic scars (HSF) is a frequent medical outcome of wound repair and often requires further therapy with treatments such as silicone gel sheets (SGS) or apoptosis-inducing agents, including bleomycin. Although widely used, knowledge regarding SGS and their mode of action is limited. Preliminary research has shown that small amounts of amphiphilic silicone present in SGS have the ability to move into skin during treatment. We demonstrate herein that a commercially available analogue of these amphiphilic siloxane species, the rake copolymer GP226, decreases collagen synthesis on exposure to cultures of fibroblasts derived from HSF. By size exclusion chromatography, GP226 was found to be a mixture of siloxane species, containing five fractions of different molecular weight. By studies of collagen production, cell viability and proliferation, it was revealed that a low molecular weight fraction (fraction IV) was the most active, reducing the number of viable cells present after treatment and thereby reducing collagen production as a result. On exposure of fraction IV to human keratinocytes, viability and proliferation were also significantly affected. HSF undergoing apoptosis after application of fraction IV were also detected via real-time microscopy and by using the TUNEL assay. Taken together, these data suggests that these amphiphilic siloxanes could be potential non-invasive substitutes to apoptotic-inducing chemical agents that are currently used as scar treatments.


Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fibroblastos , Queratinocitos , Siloxanos/farmacología , Tensoactivos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cicatriz Hipertrófica/patología , Técnicas de Cocultivo , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/fisiología , Ensayo de Materiales
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