Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug delivery applications using biodegradable polymeric microspheres are becoming an important means of delivering therapeutic agents. The aim of this work was to modulate the microporosity of poly(epsilon-caprolactone) (PCL) microcarriers to control protein loading capability and release profile. PCL microparticles loaded with BSA (bovine serum albumin) have been de novo synthesized with double emulsion solvent evaporation technique transferred and adapted for different polymer concentrations (1.7 and 3% w/v) and stabilizer present in the inner aqueous phase (0.05, 0.5 and 1% w/v). SEM (scanning electron microscope) and CLSM (confocal laser scanning microscope) analysis map the drug distribution in homogeneously distributed cavities inside the microspheres with dimensions that can be modulated by varying double emulsion process parameters. The inner structure of BSA-loaded microspheres is greatly affected by the surfactant concentration in the internal aqueous phase, while a slight influence of polymer concentration in the oil phase was observed. The surfactant concentration mainly determines microspheres morphology, as well as drug release kinetics, as confirmed by our in-vitro BSA release study. Moreover, the entrapped protein remained unaltered during the protein encapsulation process, retaining its bio-activity and structure, as shown through a dedicated gel chromatographic analytical method.
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PMID:Engineering of poly(epsilon-caprolactone) microcarriers to modulate protein encapsulation capability and release kinetic. 1791 22

A common method used to prepare polymeric nanoparticles in pharmaceutical technology is emulsion-diffusion. However, this method has several disadvantages due to the long duration of the process. At the diffusion step of conventional emulsion-diffusion, high pressure treatment could replace the addition of great quantities of water resulting in diffusion of the solvents from the internal phase to the external phase. The objective of the present study was to develop a novel method for nanoparticle formulation by combining high pressure treatment with the emulsion-diffusion method to avoid an additional diffusion step in the aqueous phase. After emulsification at 11,000 rpm, the emulsions were pressurized at 100, 200 and 300 Mpa, each for 300, 600, 900 or 1200 s. The mean size and morphology of the nanoparticles were analysed by Mastersizer, TEM and SEM. The mean size of pressurized emulsion nanoparticles was the same at 100 MPa for holding times up to 600 s. Also, the pressurized emulsion nanoparticle size increased and the peak and width of the size distribution curve was higher and slightly narrower depending on the pressure and the holding time. This study shows that pressure treatment can produce polymer membranes surrounding the oil surface owing to the precipitation of PCL, inducing the diffusion of solvent from the interior to the exterior based on TEM images. From these results, it is believed that high pressure treatment should be considered as a successful alternative for preparing nanoparticles.
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PMID:Development of a novel nanocapsule formulation by emulsion-diffusion combined with high hydrostatic pressure. 1860 95

In this contribution, PCL (poly-epsilon caprolactone) scaffolds were prepared by solvent-casting/particle-leaching technique in the presence of two pore formers, PEG(4000) or sucrose molecules in different quantities (0, 10, 20, 30, 40, 50, 55 w/w% PEG(4000)/PCL; 10, 20 w/w% Sucrose/PCL). The surface and bulk properties of the resulting scaffolds were studied by SEM, DSC and FTIR. SEM photographs showed that, macroporosity was obtained in the PCL structures prepared with sucrose crystals while microporous structure was obtained in the presence of PEG(4000) molecules. Average pore diameters calculated from SEM photographs were 40.1 and 191.2 mum for 40% PEG(4000)/PCL and 10% Sucrose/PCL scaffolds, respectively. The DSC and FTIR results confirmed that there is no any interaction between pore formers and PCL during structural formation, and both pore formers, PEG(4000) and sucrose, remained independently in the scaffolds. L929 mouse fibroblast cells were seeded onto PCL structures and maintained during 7 days to evaluate cell proliferation. Cell culture results showed that, 10% Sucrose/PCL scaffold was the most promising substrate for L929 cell growth due to 3-D architecture and macroporous structure of the scaffold.
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PMID:Comparison of cellular proliferation on dense and porous PCL scaffolds. 1872 92

Nerve tissue engineering is one of the most promising methods to restore nerve systems in human health care. Scaffold design has pivotal role in nerve tissue engineering. Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue-engineering applications. Random and aligned PCL/gelatin biocomposite scaffolds were fabricated by varying the ratios of PCL and gelatin concentrations. Chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by FTIR, porometry, contact angle and tensile measurements, while the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. PCL/gelatin 70:30 nanofiber was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (C17.2 cells). MTS assay and SEM results showed that the biocomposite of PCL/gelatin 70:30 nanofibrous scaffolds enhanced the nerve differentiation and proliferation compared to PCL nanofibrous scaffolds and acted as a positive cue to support neurite outgrowth. It was found that the direction of nerve cell elongation and neurite outgrowth on aligned nanofibrous scaffolds is parallel to the direction of fibers. PCL/gelatin 70:30 nanofibrous scaffolds proved to be a promising biomaterial suitable for nerve regeneration.
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PMID:Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. 1875 94

Previously, we have demonstrated that 2,2-bis(2-oxazoline) linked poly-epsilon-caprolactone (PCL-O) is degraded in vitro enzymatically by surface erosion which could enable the novel use of this material for drug delivery and other biomedical applications. In this study, degradation, erosion (weight loss) and toxicity of PCL-O poly(ester-amide)s were evaluated in vivo. PCL and three PCL-O polymers with different PCL block lengths (M(n): 1500, 3900, 7500 g/mol) were melt-pressed in the form of discs and implanted subcutaneously in Wistar rats (dose approximately 340 mg/kg) for 1, 4 and 12 weeks. With implantation for 12 weeks, up to 16.5% weight loss of polymer discs was measured for the most extensively linked PCL-O polymer (block length 1500 g/mol) whereas practically no weight loss was observed with the other polymers. NMR, DSC and SEC studies as well as SEM micrographs before and after implantation and in vitro hydrolysis studies indicate that enzyme based surface erosion of PCL-O polymers occurred in vivo. The in vivo evaluation based on results from hematology, clinical chemistry and histology of the implantation area and main organs (i.e. heart, lung, liver, kidney, spleen and brain) demonstrated that PCL-O polymers are biocompatible and safe, enzyme sensitive biomaterials.
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PMID:In vivo implantation of 2,2'-bis(oxazoline)-linked poly-epsilon-caprolactone: proof for enzyme sensitive surface erosion and biocompatibility. 1902 79

The purpose of this study was to develop a novel polymer cuff for the local delivery of alpha-lipoic acid (ALA) to inhibit neointimal formation in vivo. The polymer cuff was fabricated by incorporating the ALA into poly- (D,L-lactide-co-caprolactone) 40:60 (PLC), with or without methoxy polyethylene glycol (MethoxyPEG). The release kinetics of ALA and in vitro degradation by hydrolysis were analyzed by HPLC and field emission scanning electron microscopy (FE-SEM), respectively. In vivo evaluation of the effect of the ALA-containing polymer cuff was carried out using a rat femoral artery cuff injury model. At 24 h, 48% or 87% of the ALA was released from PCL cuffs with or without MethoxyPEG. FE-SEM results indicated that ALA was blended homogenously in the PLC with MethoxyPEG, whereas ALA was distributed on the surface of the PLC cuff without MethoxyPEG. The PLC cuff with MethoxyPEG showed prolonged and controlled release of ALA in PBS, in contrast to the PLC cuff without MethoxyPEG. Both ALA-containing polymer cuffs had a significant effect on the inhibition of neointimal formation in rat femoral artery. Novel ALA-containing polymer cuffs made of PLC were found to be biocompatible and effective in inhibiting neointimal formation in vivo. Polymer cuffs containing MethoxyPEG allowed the release of ALA for one additional week, and the rate of drug release from the PLC could be controlled by changing the composition of the polymer. These findings demonstrate that polymer cuffs may be an easy tool for the evaluation of anti-restenotic agents in animal models.
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PMID:Fabrication of an alpha-lipoic acid-eluting poly-(D,L-lactide-co-caprolactone) cuff for the inhibition of neointimal formation. 1928 97

Nanofibrous scaffolds have morphological similarities to native extracellular matrix and have been considered as candidate scaffolds in tissue engineering. However, there is no report on the effect of the thickness of nanofibrous scaffold on cell behavior. In this study poly (epsilon-caprolactone) (PCL) nanofibrous scaffolds with thicknesses of 0.1 and 0.6 mm were fabricated by electrospinning. Properties of PCL nanofibrous scaffolds were measured by contact angle and air permeability measurements while the morphology of the nanofibers was observed by SEM. Mouse embryonal carcinoma stem cells (P19), monkey epithelial kidney cells (Vero), Chinese hamster ovary cells (CHO) and mouse mesenchymal stem cells (MSCs) were seeded on PCL nanofibrous scaffolds with thicknesses of 0.1 and 0.6 mm. Air permeability measurements showed that air permeability decreases with the increase in the thickness of nanofibrous scaffolds, and contact angle measurements revealed a contact angle of 118 degrees for electrospun PCL nanofibers. The MTT assays showed that the proliferation of the cells was influenced by the thickness of the nanofibrous scaffold. Scaffolds with a thickness of 0.6 mm were found to provide a better substrate for cell proliferation, possibly due to more dimensional stability. Therefore, regardless of cell origin, thicker scaffolds provide a better substrate for cell proliferation, possibly due to the higher dimensional stability and tightness of thicker scaffolds.
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PMID:The thickness of electrospun poly (epsilon-caprolactone) nanofibrous scaffolds influences cell proliferation. 1944 Sep 90

Poly(epsilon-caprolactone) (PCL) implants containing praziquantel (PZQ), a broad-spectrum antiparasite drug, are fabricated by injection molding and characterized in terms of content uniformity, morphology, drug physical state and stability. In vitro drug release from the implants is also studied. It is found that drug is dispersed uniformly in all implants and keeps stable over 365 days at 4 degrees C/60% RH. X-ray diffraction analysis reveals that PZQ exists primarily in its crystalline state in implants with high drug contents (50% and 25%). All implants exhibit similar release behaviors and about 70% of the drug is released after 365 days. The cross-sections of all implants present two distinct zones (i.e. peripheral white zone and inner pink zone) and the boundary between the two zones changes as time progresses. Drug content in the white zone is very low (less than 1%), but drug content in the pink zone is almost the same as the predefined value. Porous structures in the white zone but dense structures in the pink zone are observed by SEM. Obvious PCL degradation occurs till up to 365 days. These results show that the release process of PZQ is a gradual diffusion from the exterior to the interior of the implants.
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PMID:Characterization and in vitro release of praziquantel from poly(epsilon-caprolactone) implants. 1944 18

The aim of current study is to investigate the in vitro and in vivo behavior of dental pulp stem cells (DPSCs) seeded on electrospun poly(epsilon-caprolactone) (PCL)/gelatin scaffolds with or without the addition of nano-hydroxyapatite (nHA). For the in vitro evaluation, DNA content, alkaline phosphatase (ALP) activity and osteocalcin (OC) measurement showed that the scaffolds supported DPSC adhesion, proliferation, and odontoblastic differentiation. Moreover, the presence of nHA upregulated ALP activity and promoted OC expression. Real-time PCR data confirmed these results. SEM micrographs qualitatively confirmed the proliferation and mineralization characteristics of DPSCs on both scaffolds. Subsequently, both scaffolds seeded with DPSCs were subcutaneously implanted into immunocompromised nude mice. Scaffolds with nHA but without cells were implanted as control. Histological evaluation revealed that all implants were surrounded by a thin fibrous tissue capsule without any adverse effects. The cell/scaffold composites showed obvious in vivo hard tissue formation, but there was no sign of tissue ingrowth. Further, the combination of nHA in scaffolds did upregulate the expression of specific odontogenic genes. In conclusion, the incorporation of nHA in nanofibers indeed enhanced DPSCs differentiation towards an odontoblast-like phenotype in vitro and in vivo.
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PMID:The performance of dental pulp stem cells on nanofibrous PCL/gelatin/nHA scaffolds. 1955 87

In the present study, porous PCL (poly (epsilon-caprolactone)) scaffolds were prepared through a melted extrusion manufacturing (MEM) machine, and carboxylate groups were formed on the surfaces of specimen by hydrolyzation with NaOH aqueous solutions. Apatite precursor was introduced on the surfaces of specimens with CaCl2 and K2 HPO4 under vacuum condition, and mineralization study was applied to these specimens. The results showed that the hydrophilicity of PCL surface was improved with the introduction of carboxylate groups, and the contact angle of surface was decreased to 26.52 degrees. A dense and uniform bone-like layer was confirmed to be formed on the surface of Ca-P treated specimens after mineralizing for less than 24 h in SBF by SEM and EDAX.
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PMID:[Preparation of novel bioactive PCL bone tissue engineering scaffold]. 1963 71


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