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)

Previously we have recrystallized estradiol with various organic solvents and investigated solvate molecules within estradiol crystals by using CP/MAS solid-state NMR. To investigate the effect of recrystallization solvents on the physicochemical properties of recrystallized estradiol, four different crystal habits of estradiol were recrystallized and their physicochemical properties were characterized by optical microscopy, solubility, and FT-IR measurements. Various crystal habits in size and shape were produced by the interaction between the estradiol and different solvents. Although the estradiol crystal habits prepared from ethanol and methanol had larger particle size, they were more soluble in PBS than those recrystallized from isopropanol and acetone. In spite of the low solubilities, the estradiols prepared from isopropanol and acetone were released in PBS and permeated through the hairless mouse skin similar to the others. Thus, although microscopic observation of recrystallized estradiols revealed that the estradiol had different crystal habits, the release and permeation properties of different estradiol crystals might be independent on the solvate molecules associated with the solvent used for recrystallization.
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PMID:Solvent effects on physicochemical behavior of estradiols recrystallized for transdermal delivery. 1827 16

Quinine is the first line treatment in severe P. falciparum malaria and nocturnal leg cramps and a fast, convenient delivery method of this drug quinine is needed. The purpose of this study was to investigate in vitro the sublingual route for the delivery of quinine. Permeation studies were carried out with Franz diffusion cells containing sublingual mucosa membranes with PBS receptor phase and dosed with solutions of quinine hydrochloride or quinine/2-hydroxypropyl-beta-cyclodextrin complexes. Receptor phase samples were taken 2 hourly over a 12h period and quinine was determined by reverse-phase HPLC analysis. The ventral surface of the tongue was significantly more permeable than porcine floor of the mouth (p<0.05) and there was no significant effect of freezing on the ventral surface of the tongue (p 0.2444). The presence of saliva caused a decrease in the permeation of quinine across the ventral surface of the tongue by up to 68%. Inclusion complexation between quinine and 2-HP-beta-CD was supported by (1)H NMR spectral data, and an ethanol vehicle provided the highest quinine flux from the inclusion complex solutions compared to deionised water and PEG. Overall, the data support further investigations into the clinical use of sublingual quinine, particularly for children with falciparum malaria or patients with nocturnal leg cramps. Use of quinine/cyclodextrin inclusion complexes may circumvent compliance issues due to bitter taste.
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PMID:Permeation of quinine across sublingual mucosa, in vitro. 1883 45

A series of amphiphilic alternative block polyurethane copolymers based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) and poly(ethylene glycol) (PEG) were synthesized by a coupling reaction between P3/4HB-diol and PEG-diisocyanate, with different 3HB, 4HB, PEG compositions and segment lengths. Stannous octanoate was used as catalyst. The chemical structure, alternative block arrangement, molecular weight and distribution were systematically characterized by FTIR, (1)H NMR, GPC and composition analysis. The thermal property was studied by DSC and TGA. Platelet adhesion study revealed that the alternative block polyurethanes possess excellent hemocompatibility. CCK-8 assay illuminated that the non-toxic block polyurethanes maintain rat aortic smooth muscle cells (RaSMCs) good viability. The in-vitro degradation of the copolymers in PBS buffer solution and in lipase buffer medium was investigated. Results showed that the copolymer films exhibit different degradation patterns in different media from surface erosion to diffusion bulk collapsing. The synthetic methodology for the alternative block polyurethanes provides a way to control the exact structure of the biomaterials and tailor the properties to subtle requirements.
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PMID:Alternative block polyurethanes based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) and poly(ethylene glycol). 1923 Sep 67

The present investigation was aimed at exploring dendrimer-mediated solubilization and formulation development followed by in vitro, in vivo assessment of piroxicam (PXM) nanocomposite. For this, two dendrimer generations (3.0G and 4.0G) were synthesized and characterized by IR, (1)H NMR spectroscopic and electron microscopy techniques. The optimized formulations containing 0.2% w/v of PXM loaded PAMAM dendrimer at pH 7.4 referred to as 0.2-D(3)P(7.4) (3.0G) and 0.2-D(4)P(7.4) (4.0G) resulted in significant enhancements of PXM solubility approximately by 107- and 222-fold, respectively. The in vitro release behavior of PXM from the formulation in medium-I (PBS 7.4) and medium-II (PBS with 1% albumin) and stability studies were also favorable. Pharmacokinetic study showed higher area under curve (AUC(0-->t); microg/mL/h) of 293.78 +/- 2.04 and 321.54 +/- 2.37 with optimized 0.2-D(3)P(7.4) and 0.2-D(4)P(7.4) formulations, respectively, as opposed to 279.11 +/- 1.48 with plain PXM. The elimination half-life of the drug encapsulated in the formulation was significantly higher (0.2-D(3)P(7.4), 36.6 and 0.2-D(4)P(7.4), 41.1; h) than that of pure drug (33.7 h; p < 0.005), and the overall elimination rate constant of formulations was also less as compared to free drug (p < 0.005). Pharmacodynamic assessment by rat-paw model of 0.2-D(3)P(7.4) and 0.2-D(4)P(7.4) formulations displayed inhibition levels of 54.21 +/- 1.25% and 59.33 +/- 0.63%, respectively, which are higher than those of plain PXM (41.81 +/- 2.9) formulations, after the sixth hour of administration. The second, fourth and eighth hour organ distribution data showed significantly higher recovery of PXM in rat paw with dendrimer-based formulations in comparison to plain PXM. However, comparison of overall data suggested 4.0G-based formulations to be superior to 3.0G as well as pure PXM.
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PMID:Dendimer-mediated solubilization, formulation development and in vitro-in vivo assessment of piroxicam. 1923 41

Poly lactic acid (PLA) is one of widely used biodegradable polymer in vaccine delivery. However, the use is restricted due to hydrophobic nature and generation of acidic microenvironment upon its degradation, rendering it unfavorable to the encapsulated antigen. In the present study we have synthesized PEG derivatized block copolymers of PLA for development of nanoparticles encapsulating HBsAg for mucosal vaccination against hepatitis B. The copolymers of compositions AB, ABA and BAB (PLA as A-block and PEG as B-block) were synthesized and characterized by 1H NMR spectroscopy and gel permeation chromatography. Nanoparticles were characterized to determine the effect of copolymer. Among all, BAB produced nanoparticles of smallest size and lowest zeta potential, suggesting highest PEG density on their surface. The in vitro release experiments were performed in PBS (pH7.4). SDS-PAGE analysis confirmed the structural stability and integrity of the released antigen. Results were compared for immunogenicity with plain PLA nanoparticles and conventional alum-HBsAg based vaccine. BAB nanoparticles produced better humoral response as compared to other polymeric nanoparticles. The extent of humoral response obtained in single dose of BAB nanoparticles was comparable to the response produced by alum based vaccine (which received a booster dose). Block copolymeric nanoparticles also produced better sIgA level at all local and distal mucosal sites as compare of PLA nanoparticles, where alum based formulation failed to give any considerable response. Additionally, IgG1 and IgG2a isotype were determined to confirm the T(H)1/T(H)2 mixed immune response. These data demonstrate the potential of BAB nanoparticles as mucosal vaccine delivery system capable of eliciting high and prolonged immune response.
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PMID:Synthesis, characterization and evaluation of novel triblock copolymer based nanoparticles for vaccine delivery against hepatitis B. 1923 19

Humanin (HN) is a recently identified neuroprotective peptide able to inhibit neurotoxicity induced by various insults which can be related to Alzheimer disease (AD) as well as to cell death induced by other stimuli. Previous CD and NMR studies demonstrated that HN adopts an unordered conformation in water, a alpha-helix conformation in 30% TFE, and a beta-sheet structure in PBS. Furthermore, other studies clearly indicated HN as a secreted peptide, able to prevent neuronal cell death caused by amyloid beta (Abeta) derivatives. Although Abeta was found to interact with neuronal membranes, currently there is not experimental evidence unveiling HN interaction with membranes. In this paper a spin labeling technique coupled with electron paramagnetic resonance (EPR) and circular dichroism (CD) has been used to study the structure and dynamics of HN in solution and for the first time in the presence of model cerebral cortex membranes (CCM). We have demonstrated that HN has a great tendency to aggregate even at low concentrations in water solutions at different ionic strengths and monomerizes in the TFE apolar environment. We also showed that HN slightly perturbs model CCM at the surface assuming a clear beta-sheet conformation. In addition, HN increases the fluidity of the bilayer core without penetrating into the membrane.
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PMID:Humanin structural versatility and interaction with model cerebral cortex membranes. 1937 54

In the presence of the nonionic alkyloxyethylene surfactant n-dodecylpentaoxyethylene glycol ether (C12E5), the anionic conjugated polyelectrolyte (CPE) poly{1,4-phenylene-[9,9-bis(4-phenoxy-butylsulfonate)]fluorene-2,7-diyl} (PBS-PFP) dissolves in water, leading to a blue shift in fluorescence and dramatic increases in fluorescence quantum yields above the surfactant critical micelle concentration (cmc). No significant changes were seen with a poly(ethylene oxide) of similar size to the surfactant headgroup, confirming that specific surfactant-polyelectrolyte interactions are important. From UV-visible and fluorescence spectroscopy, dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and electrical conductivity, together with our published NMR and small-angle neutron scattering (SANS) results, we provide a coherent model for this behavior in terms of breakup of PBS-PFP clusters through polymer-surfactant association leading to cylindrical aggregates containing isolated polymer chains. This is supported by molecular dynamics simulations, which indicate stable polymer-surfactant structures and also provide indications of the tendency of C12E5 to break up polymer clusters to form these mixed polymer-surfactant aggregates. Radial electron density profiles of the cylindrical cross section obtained from SAXS results reveal the internal structure of such inhomogeneous species. DLS and cryo-TEM results show that at higher surfactant concentrations the micelles start to grow, possibly partially due to formation of long, threadlike species. Other alkyloxyethylene surfactants, together with poly(propylene glycol) and hydrophobically modified poly(ethylene glycol), also solubilize this polymer in water, and it is suggested that this results from a balance between electrostatic (or ion-dipole), hydrophilic, and hydrophobic interactions. There is a small, but significant, dependence of the emission maximum on the local environment.
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PMID:Solubilization of poly{1,4-phenylene-[9,9-bis(4-phenoxy-butylsulfonate)]fluorene-2,7-diyl} in water by nonionic amphiphiles. 1937 13

Degradation and drug release behavior of thermogelling hydrogel of poly(epsilon-caprolactone-co-glycolide)-poly(ethylene glycol)-poly(epsilon-caprolactone-co-glycolide) [P(CL-GL)-PEG-P(CL-GL) (1880-1540-1880)] triblock copolymer were investigated. The copolymer aqueous solution (25 wt%) underwent sol-gel transition at 35 degrees C as the temperature increased and formed a stable gel at body temperature. After incubation in PBS buffer solution (0.1 M) at 37 degrees C, the gel degraded completely into a viscous liquid at 14th week. Chemical microstructural analysis of the degraded samples by (1)H-NMR revealed the degradation occurring mainly on the glycolyl sequences of the copolymer. The pH value of the gel buffer solution maintained neutral during the initial 8 weeks, which may be beneficial for the preservation of activity of pH-sensitive drugs. Incorporation of drugs into the gel was formulated at room temperature without the use of any organic solvent. The gel formed a controlled release depot with delivery times of 12, 32, and 25 days for isoniazid, rifampicin and bovine serum albumin, respectively. Controlled release of hydrophobic rifampicin was achieved with insignificant burst effect due to the distribution of the drug mainly in the hydrophobic polyester regions of the gel.
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PMID:Biodegradable thermogelling hydrogel of P(CL-GL)-PEG-P(CL-GL) triblock copolymer: degradation and drug release behavior. 1945 26

Myocardial stunning is characterized by a metabolic uncoupling from function as mitochondrial tricarboxylic acid (TCA) cycle and oxygen consumption remain normal despite reduced contractility. Overexpression of the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA1) in hearts has recently been reported to reduce dysfunction at reperfusion. In this study we determine whether the metabolic coupling to function improves with SERCA treatment. PBS (control) or adenovirus carrying the cDNA for SERCA1 was delivered via coronary perfusion in vivo to Sprague-Dawley rat hearts. Three days following gene transfer, isolated hearts were perfused with 0.4 mM [2,4,6,8,10,12,14,16-13C8] palmitate and 5 mM glucose, and subjected to 15-min ischemia followed by 40-min reperfusion. Consistent with myocardial stunning, rate pressure product (RPP) and left ventricular developed pressure (LVDP) were depressed 30-40% (p<0.05) in the PBS group. With SERCA1 overexpression, dP/dt was 20% greater than controls (p<0.05), and LVDP and RPP recovered to pre-ischemic values. From dynamic 13C NMR, TCA cycle flux at reperfusion was similar to pre-ischemic values for both groups. Therefore, the efficiency of coupling between cardiac work and TCA cycle flux was restored with SERCA1 treatment. Oxidative efficiency was also enhanced with SERCA1 as cytosolic NADH transport into the mitochondria was significantly greater compared to the PBS group. In addition, the phosphocreatine to ATP ratio (PCr/ATP) was not compromised with SERCA1 expression, despite enhanced function, and depressed fatty acid oxidation at 40-min reperfusion in the PBS group was not reversed with SERCA1. These data demonstrate that metabolic coupling and NADH transport are significantly improved with SERCA1 treatment.
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PMID:SERCA1 expression enhances the metabolic efficiency of improved contractility in post-ischemic heart. 1974 94

A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4'-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by (1)H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as approximately 30 degrees C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37 degrees C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37 degrees C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications.
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PMID:Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering. 1978 43


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