Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biodegradable hydrogel nanoparticles were prepared from glycidyl methacrylate dextran (GMD) and dimethacrylate poly(ethylene glycol) (DMP). GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine (DMAP) using dimethylsulfoxide (DMSO) as an aprotic solvent. DMP was synthesized from poly(ethylene glycol) (PEG) and methacryloyl chloride. GMD/DMP (abbreviated as DP) hydrogel was prepared by radical polymerization of GMD and DMP using ammonium peroxydisulfate (APS) as an initiator and UV curing. DP hydrogel nanoparticles were obtained by diafiltration method using DMSO solution. The GMD and DMP were characterized by fourier transform infrared spectroscopy. Fluorescence probe technique was used to investigate the self-assembly of DP in water using pyrene as a hydrophobic probe. The critical association concentration (CAC) was determined to be 5.6 x 10(-2) g/l. The shape of DP hydrogel nanoparticles was spherical when observed by transmission electron microscope (TEM). The size range of DP hydrogel nanoparticles was about 20 approximately 50 nm. The hydrodynamic size of DP hydrogel nanoparticles was measured by photon correlation spectroscopy (PCS) and gradually increased with time in PBS (0.1 M, pH 7.4). Drug release study was performed using clonazepam (CNZ) as a hydrophobic model drug. In vitro release rate of CNZ from the DP hydrogel nanoparticles was dependent on the existence of dextranase and the pH of the release medium.
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PMID:Self-assembled hydrogel nanoparticles composed of dextran and poly(ethylene glycol) macromer. 1100 May 47

Insulin-loaded microparticles were produced from blends of poly(ethylene glycol) (PEG) with poly (L-lactide) (PLA) homopolymer and poly (DL-lactide co-glycolide) copolymers (PLG) using a water-in-oil solvent extraction method. The dispersed phase was composed of PLG/PEG or PLA/PEG dissolved in dichloromethane, and the continuous phase was methanol containing 10% PVP. Characteristics, including particle size distribution, insulin loading capacity and efficiencies, in vitro release, degradation and stability, were investigated. The stability of insulin associated with microparticles prepared using PEG and 50:50 PLG and PLA was analysed by HPSEC and quantified by peak area following incubation in PBS at 37 degrees C for up to 1 month. Insulin was successfully entrapped in the PLG/PEG and PLA/PEG microparticles with trapping efficiencies up to 56 and 48%, loading levels 17.8 and 10.6% w/w, and particle sizes 8 and 3 microm, respectively. The insulin-loaded PLG/PEG and PLA/PEG microparticles were capable of controlling the release of insulin over 28 days with in vitro delivery rates of 0.94 and 0.65 microg insulin/mg particles/day in the first 4 days and a steady release with rate of 0.4 and 0.43 microg insulin/mg particles/day over the following 4 weeks, respectively. Extensive degradation of the PLG/PEG microparticles also occurred over 4 weeks, whereas the use of PLA/PEG blends resulted in a stable microparticle morphology and much reduced fragmentation and aggregation of the associated insulin.
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PMID:The stability of insulin in biodegradable microparticles based on blends of lactide polymers and polyethylene glycol. 1106 21

Poly(propylene fumarate-co-ethylene glycol) random (PPF-1) and block (PPF-2) copolymer oligomers were prepared. Comparing the setting characteristics of PPF-1 and PPF-2 with comonomer n-vinyl pyrrolidone (n-VP) and swelling characteristics of cured PPF-1 and PPF-2, lower setting temperature and setting time was observed with the former leading to higher swelling coefficient and lower cross link density in the cured PPF-1. Due to the high swelling coefficient and low setting exothermic temperature associated with PPF-1, the bone cement was prepared from PPF-1, n-VP and hydroxyapatite (HAP). The in vitro degradation studies reveal lesser weight loss and deformation of PPF-1/n-VP/HAP based cured resin in Ringer's solution and phosphate buffered saline in comparison with that of PPF-1/n-VP cured resin. Though the bone cement composite has adequate mechanical properties with HAP, the compressive strength and modulus of the composite aged in Ringer's solution and PBS reduced appreciably which is due to extensive hydration and plasticization by the PEG unit. However, the bone-binding and bond strength of the bone cement determined as the load for separation of bones was found to be similar to that of fast setting calcium phosphate-atelocollagen (5%) bone cement. The bone cement PPF-1/n-VP/HAP could be used as scaffold for correcting the bone defects.
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PMID:Studies on poly(propylene fumarate-co-ethylene glycol) based bone cement. 1108 40

Surface-modified albumin nanoparticles were prepared from two poly(ethylene glycol)-human serum albumin conjugates: poly(thioetheramido acid)-poly(ethylene glycol) copolymer-grafted HSA (HSA-PTAAC-PEG) and methoxy poly(ethylene glycol)-grafted HSA (HSA-mPEG). Rose bengal (RB) was used as a model drug for encapsulation into the nanoparticles either during the particle production or by adsorption post particle preparation. The drug incorporation and release was affected by the different production methods and the different polymer compositions. When RB was loaded in HSA and HSA/HSA-PTAAC-PEG nanoparticles, up to 5% (w/w) drug content was achieved. The drug loading in HSA-mPEG nanoparticles was much lower and the results from the microcalorimetry study indicated that the low loading efficiency was due to less drug-protein binding sites available in the HSA-mPEG molecule as compared to the HSA molecule. The release of RB from the albumin nanoparticles was very slow in PBS and dramatically accelerated in the presence of trypsin. Compared with unmodified nanoparticles, the slower release of RB from the surface-modified HSA nanoparticles in the presence of the enzyme suggested that the existence of a steric hydrophilic barrier on the surface of the nanoparticles made digestion of the nanoparticles more difficult.
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PMID:Preparation and characterisation of rose Bengal-loaded surface-modified albumin nanoparticles. 1124 13

The first paper of this series presented the fabrication and characterization of POE-PEG-POE triblock copolymeric microspheres containing protein. In this paper, we focus on the polymer erosion and the mechanism of protein release. Fourteen-week in vitro behaviors of POE-PEG-POE microspheres loaded with bovine serum albumin (BSA) have been monitored. SEM micrographs reveal that after 14-week incubation in PBS buffer, pH 7.4, 37 degrees C, the polymeric particles remain spherical despite mass loss of almost 90%. On the other hand, molecular weight undergoes a high initial loss of 38% and 44% during the first 2-week incubation for POE-PEG(5%)-POE and POE-PEG(10%)-POE, respectively. Then, it keeps relatively unchanged over 12 weeks. However, POE-PEG(20%)-POE copolymer provides a better compatibility between the POE and PEG blocks. Hydrolysis is homogeneous through the polymer backbone. Thus, its molecular weight remains relatively constant and mass loss shows quite sustained over the 14-week in vitro release. The similar phenomena are observed in the polydispersity index of the degrading copolymers. SDS-PAGE of the encapsulated BSA within the POE-PEG(5%)-POE microspheres displays that the structural integrity of BSA is intact for at least 8 weeks due to a mild environment provided by the copolymer. In addition, XPS and FTIR are utilized to investigate protein behaviors in the degrading microspheres. Protein release from the POE-PEG-POE microspheres shows a biphasic pattern, characterized by an initial stage followed by a non-detectable release. The non-release phase is dominated by either slow polymer degradation or dense microsphere matrix structures. The microsphere formulation is optimized and a sustained protein release over 2 weeks is achieved by using POE-PEG(20%)-POE at a high protein loading.
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PMID:POE-PEG-POE triblock copolymeric microspheres containing protein. II. Polymer erosion and protein release mechanism. 1145 3

This study employed two water-soluble and nontoxic molecules, sucrose and glycerol, to enhance the permeability of PEG-PHEMA polymer gels coated onto 100 kDa molecular weight cutoff polyethersulfone (PES) microdialysis probes. Sucrose precoating of the probes prior to prepolymer coating prevented penetration of the prepolymer into the microdialysis membrane. Glycerol mixed with the prepolymer introduced porosity in the polymer coating upon curing. The sucrose and glycerol were completely removed by soaking in PBS after curing of the polymer coat on the probe tip. Polymer coated probe glucose permeability was tested by measuring glucose recovery from PBS solutions. Biocompatibility was assessed by measuring glucose recovery of polymer coated probes from heparanized whole porcine blood. Results show that the sucrose and glycerol treatments yielded polymer coated probes with glucose permeability nearly equal to bare probes when tested in PBS solution, but that this increased permeability was not observed when tested in whole blood. This suggests that the thickness of the polymer films (10-100 microm), while not a limiting factor in PBS solution, may have presented a diffusion barrier to glucose recovered from blood. Surprisingly, however, the polymer coated probes exhibited less thrombus formation that did the bare probes after blood exposure.
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PMID:Water-soluble treatments to enhance glucose permeability of protein-resistant polymer overlayers. 1146 78

Covalent binding of 4 molecules of phosphatidylcholine palmitoyl to human recombinant superoxide dismutase (SOD) results in a compound (lecithinized SOD) that has a longer half-life and greater affinity to the cell membrane than unmodified SOD. We investigated whether lecithinized SOD played a protective role against myocardial ischemia-reperfusion injuries in rats. Rats underwent 45 min of myocardial ischemia by occluding the left coronary artery followed by 120 min of reperfusion. They were randomly assigned to receive either lecithinized SOD, polyethylene glycol conjugated SOD (PEG-SOD), unmodified SOD, free lecithin derivative, or PBS intravenously at 5 min prior to reperfusion. Myocardial infarct area assessed by TTC staining was smaller in lecithinized SOD group than PEG-SOD, unmodified SOD, free lecithin derivative or control group. Blood pressure and heart rate was similar in each group. ELISA demonstrated SOD level in the heart was significantly high in lecithinized SOD group, especially in the heart of ischemia at risk. Although serum SOD level of PEG-SOD was as high as lecithinized SOD, SOD level of the heart was low. These data suggested lecithinized SOD had a protective effect in myocardial ischemia-reperfusion injuries through its increased bioavailability.
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PMID:Lecithinized Cu, Zn-superoxide dismutase limits the infarct size following ischemia-reperfusion injury in rat hearts in vivo. 1147 86

Monoclonal antibodies against glutamic acid decarboxylase (anti-GAD) were modified with poly(ethylene glycol) (PEG), and the resulting conjugates were characterized. Monoclonal anti-GAD antibodies were purified from ATCC HB184 hybridoma cells by either cell culture supernatant or ascites fluid from BALB/c mice. Polyclonal rabbit IgG antibodies were also used as a model protein. Polyclonal rabbit IgG or purified anti-GAD was modified by PEG (MW = 5000 or 20000 Da) through either the lysine residues or through the carbohydrate moiety. Lysine modification was performed in PBS (pH 7.4) or 0.1 M borate (pH 9.2) by adding a molar excess (5-80) of a succinimidyl activated propionic acid terminated mPEG (SPA-PEG) while stirring at room temperature. Carbohydrate modifications were performed in PBS (pH 6.2) by first oxidizing the antibody with sodium periodate followed by incubation with hydrazide-terminated PEG followed by reduction with sodium cyanoborohydride. The degree of modification was assessed by 1H NMR or TNBS (trinitrobenzenesulfonic acid). Circular dichroism (CD) spectra were obtained for lysine-modified rabbit IgG at various degrees of modification ranging from 5 to 60 PEG per antibody. Binding was assessed using an ELISA method with GAD or rabbit anti-mouse-IgG (H+L) coated plates. The TNBS and 1H NMR analysis of the modified antibody showed reasonably similar results from 5 to 60 PEG per antibody. The 1H NMR method showed greater sensitivity at low modifications (below 20:1) and was fairly linear up to about 60 PEG per antibody. The CD spectra of the polyclonal rabbit IgG showed only small differences at variously modified antibody. The binding affinity of anti-GAD is lower for all PEG modifications with respect to unmodified anti-GAD. Modifications at pH 7.4 show lower binding to GAD than modifications at pH 9.2. Binding to GAD or anti-mouse-IgG is decreased as the degree of modification is increased. Lysine modifications showed lower binding to GAD or anti-mouse-IgG than carbohydrate modifications. Binding to GAD or anti-mouse-IgG is lower for PEG20000-modified anti-GAD with respect to PEG5000-modified anti-GAD.
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PMID:Physicochemical characterization of poly(ethylene glycol)-modified anti-GAD antibodies. 1171 75

Arterial restenosis is responsible for the high failure rates of vascular reconstruction procedures. Local sustained drug delivery has shown promise in the prevention of restenosis. The drug release rate from mithramycin-loaded EVA matrices (0.1%) was evaluated, and their antirestenotic effect was studied in the rat carotid model and rabbit model of vascular grafts. The modulation of c-myc expression by mithramycin treatment was examined by immunohistochemistry in the rat carotid model. The proliferative response of injured rat arteries was studied by bromdeoxyuridine (BrdU) immunostaining. The impact of mithramycin treatment on vasomotor responses of the venous segments grafted into arterial circulation was studied ex vivo using vasoreactive compounds. Mithramycin was released exponentially from EVA matrices in PBS. Matrices co-formulated with PEG-4600 revealed enhanced release kinetics. The perivascular implantation of drug-loaded EVA-PEG matrices led to 50% reduction of neointimal formation, and reduced the c-myc expression and BrdU labeling in comparison to control implants. Decreased sensitivity of mithramycin-treated grafts to serotonin-induced vasoconstriction was observed. Local perivascular mithramycin treatment limits the functional alteration caused by the grafting of venous segments in high-pressure arterial environment, and potently inhibits stenosis secondary to grafting and angioplasty injury. The antirestenotic effect is associated with reduced c-myc expression and with subsequent decrease in SMC proliferation.
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PMID:Local delivery of mithramycin restores vascular reactivity and inhibits neointimal formation in injured arteries and vascular grafts. 1173 85

A series of graft copolymers consisting of either poly(N-isopropylacrylamide) (PNiPAAm) or poly(N,N-diethylacrylamide) (PDEAAm) as a thermo-responsive component in the polymer backbone and poly(ethyleneglycol) (PEG) were immobilized as thin films and cross-linked on a fluoropolymer substrate using low-pressure argon plasma treatment. The surface-immobilized hydrogels exhibit a transition from partially collapsed to completely swollen, which is in the range of 32-35 degrees C and corresponds to the lower critical solution temperature of the soluble polymers. The hydrogels were used as cell carriers in culture experiments with L929 mouse fibroblast cells to probe for cell adhesion, proliferation, and temperature-dependent detachment of cell layers. The fibroblast cells adhere, spread, and proliferate on the hydrogel layers at 37 degrees C and become completely detached after reducing the temperature by 3 K. The cell release characteristics were further correlated to the swelling and collapsing behavior of the hydrogel films and the polymer solutions as measured in PBS solution and RPMI cell cultivation medium. It could be shown that, long before the swelling has completed upon temperature reduction, the cells detach. This can be attributed to the large content of PEG present in the hydrogel, which weaken the cell adhesion strength to the hydrogel layers.
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PMID:Thermo-responsive PNiPAAm-g-PEG films for controlled cell detachment. 1460 3


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