Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An intravenous infusion of Fluosol enhanced significantly the t-PA thrombolysis of the arterio-venous shunt made by insertion of 125I-fibrin clot in rabbits. The plasma radioactivity released through thrombolysis increased in both time and dose-dependent manner after the administration of t-PA. Fluosol in combination with t-PA increased the plasma radioactivity, compared with the t-PA treatment alone at the corresponding dosage. The coronary blood flow was markedly reduced to almost zero after the thrombin injection into narrowed LCX with a clamp in open-chest dogs. An intravenous infusion of Fluosol or Pluronic F-68 solution at a dose of 15 ml/kg significantly shortened the thrombolysis time by intracoronary infusion of urokinase alone. While, little change in the QTc interval of ECG and the plasma CPK-MB activity was observed in the Fluosol group in combination with urokinase, suggesting a myocardial protective action of Fluosol possibly due to its oxygen carrying effect.
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PMID:Extended use of Fluosol emulsion in acute myocardial ischemia treatment. 139 38

Protein release from degradable polymer matrices, composed of poly(L-lactic acid) and its blends with Pluronic surfactant, was investigated with and without the aqueous coating of an adsorptive water-soluble polymer, polyethyleneimine (PEI). PEI is a highly branched cationic polymer containing primary, secondary, and tertiary amino groups in its backbone. The treatment of PEI for PLA/Pluronic blend films exhibited a remarkable decrease in the "burst" release of protein at an initial stage and a significant extension in the protein release period. Protein release profiles could be controlled by varying PEI treatment time and its concentration. Our results suggest that PEI diffuses into the polymer matrices and crosslinks protein molecules by ionic interactions. Such a PEI-protein network near the surface region of matrix may act as a diffusional barrier for further release of protein molecules.
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PMID:Controlled protein release from polyethyleneimine-coated poly(L-lactic acid)/pluronic blend matrices. 158 7

The intrinsic activity of single-chain pro-urinary-type plasminogen activator (pro-uPA) and whether its receptor (uPAR) potentiates this activity remains controversial. In this report, the pro-uPA/uPAR-(1-281)-peptide complex in solution is shown to have equivalent plasminogen-activator activity to that of active two-chain uPA (tc-uPA). However, the activity of the complex was dependent on a synthetic tripeptide, Spectrozyme plasmin (Spl, H-D-2-aminohexanoic acid(Ahx)-hexatyrosyl-lysine-p-nitroanilide), which can also be used as a chromogenic substrate for plasmin. Furthermore, this activity could be completely suppressed by commonly used carrier proteins and detergents. The pro-uPA/uPAR-(1-281)-peptide complex at 1 nM displayed similar activity to that of tc-uPA for either [Glu1]plasminogen or [Lys77]plasminogen in chromogenic assays with Spl present as the plasmin substrate. When assayed with another plasmin substrate, S2251, the pro-uPA/uPAR-(1-281)-peptide complex was unable to activate plasminogen. The pro-uPA/uPAR-(1-281)-peptide complex and tc-uPA also showed a similar extent of plasminogen activation as measured by SDS/PAGE, when incubated with plasminogen and Spl in the presence of 100 micro M aprotinin, and plasminogen activation by pro-uPA alone was also stimulated in the presence of Spl in this assay. Activation of plasminogen by the pro-uPA/uPAR-(1-281)-peptide strictly required the presence of Spl, and pro-uPA remained in single-chain form during these assays. This activity of the pro-uPA/uPAR-(1-281)-peptide complex but not that of tc-uPA was completely inhibited by human serum albumin, bovine serum albumin, Tween-80, Triton X-100, and Pluronic-F68. Taken together, the data indicates that uPAR-(1-281)-peptide itself is not sufficient to augment pro-uPA activity and the presence of an effector molecule (e.g. Spl) is required to elicit the full plasminogen-activator activity of the pro-uPA/uPAR-(1-281)-peptide complex. It remains to be seen whether there is a physiological counterpart to this phenomenon.
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PMID:Plasminogen activation by pro-urokinase in complex with its receptor--dependence on a tripeptide (Spectrozyme plasmin). 924 34

The phagocytosis of drug-loaded polymeric microspheres by white blood cells, such as neutrophils or mononuclear cells, represents the major clearance mechanism by which this foreign material is eliminated from the body. The process of phagocytosis requires the activation of the white blood cells by the microsphere surface, followed by binding and engulfment. Phagocytosis may result in the removal of the microspheres from the blood or the disease site and an inflammatory response. Therefore, we have studied the level of neutrophil activation by microspheres ( +/- opsonization) manufactured from various biomaterials or polymers. Polymer microspheres with equivalent size distributions were made from poly (DL-lactic acid) (PLA), poly(epsilon-caprolactone) (PCL), poly(methyl methacrylate) (PMMA) or a 50 : 50 blend of PLA: poly(ethylene-co-vinyl acetate) (PLA: EVA). Neutrophils were isolated from human blood and activation of these cells by microspheres was measured by chemiluminescence (CL). All four types of microspheres induced only low levels of CL, however these levels were enhanced significantly if the microspheres were pretreated with plasma or IgG suggesting an opsonization effect. The adsorption of IgG or proteins from plasma was confirmed by polyacrylamide gel electrophoresis (SDS-PAGE). The poloxamer Pluronic F127 inhibited the opsonization effect of IgG and plasma on all four types of microspheres and inhibited protein adsorption as measured by SDS-PAGE. Since neutrophil activation is part of the inflammation process in vivo, these in vitro data suggest that all four types of microspheres are likely to be inflammatory if injected into body compartments containing plasma-derived fluids. Pretreatment of the microspheres with Pluronic F127 may reduce the inflammatory potential of the microspheres.
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PMID:Neutrophil activation by plasma opsonized polymeric microspheres: inhibitory effect of pluronic F127. 1087 77

When co-precipitated with amphiphilic copolymers from DMSO, poly(D,L-lactide) (PLA) can be readily converted into stable sub-200 nm nanoparticles by addition of an aqueous phase, free of any polymeric stabilizers such as poly(vinyl alcohol) or Poloxamer. In this work, the ability of random poly(methyl methacrylate-co-methacrylic acid) copolymers (PMMA-co-MA) to stabilize PLA nanoparticles was demonstrated, and the properties of PLA/PMMA-co-MA nanoparticles were investigated. When co-precipitated with PMMA-co-MA, PLA was totally converted into nanoparticles using a polymer concentration in DMSO (Cp) below 17.6 mg ml(-1), and a PMMA-co-MA proportion above a critical value depending on the content of MA repeating units (X). For instance, the lowest PMMA-co-MA proportion required was 0.9 mg mg(-1) PLA for X = 12%, and 0.5 mg mg(-1) PLA for X = 25% (for C(PLA) = 16 mg ml(-1) DMSO). The nanoparticle diameter was essentially independent of X, the proportion of PMMA-co-MA, and the PLA molecular weight, except for oligomers for which the nanoparticle diameter was smaller. It decreased when the organic phase was diluted (126 +/- 13 nm for Cp = 17.6 mg ml(-1), and 81 +/- 5 nm for C(P) = 5.6 mg ml(-1)). The time-dependence of the stability and the degradation of PLA/PMMA-co-MA nanoparticles was discussed. One of the main advantages of this technique is the ability to control surface properties and to bring functional groups to otherwise non-functionalized PLA nanoparticles. To illustrate this, a conjugate of PMMA-co-MA25 and biotin was synthesized, and used to prepare biotinylated nanoparticles that could be detected by fluorescence and transmission electron microscopy after infiltration into ligatured rat small intestine.
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PMID:Preparation of poly(D,L-lactide) nanoparticles assisted by amphiphilic poly(methyl methacrylate-co-methacrylic acid) copolymers. 1143 78

The controlled drug delivery of hydrophilic and lipophilic drug substances via the parenteral route has gained increasing importance in the development of pharmaceutical dosage forms. In particular, the animal health industry has generated strong interest in long-term drug delivery for both companion and farm animals during the past few years. At present sustained-release injectables formed in situ for s.c./i.m. administration have become an attractive alternative to common slow release technologies such as microspheres or standard implants. In this context, technologies based on PLA/PLGA, sucrose acetate isobutyrate (SAIB) and the amphipathic molecules Poloxamer, glycerol monooleate or PEG-PLA-PEG copolymers, are discussed. Release periods from hours to months can be obtained by choosing one of these drug delivery technologies. The release times are strongly dependent on the biodegradation of the polymers and the physico-chemical properties of the drug substance used. Furthermore, the use of different solvents for the matrix-forming agents and the individual loading capacity are critically assessed. Additionally acceptance of the excipients for parenteral use by the regulatory authorities is closely considered. Scientific articles as well as patent publications are reviewed to give a wide overview of the existing approaches and their future potential for animal health products.
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PMID:Sustained-release injectables formed in situ and their potential use for veterinary products. 1248 Mar 6

A model is developed to describe protein release kinetics from injectable, polymer solution depots which undergo rapid phase inversion on injection. The model consists of a polymer-rich phase and a solvent-rich phase, consistent with experimentally observed phase inversion morphology. Equations in the polymer-rich phase are based on diffusion-reaction mass balances for solvent, water and dissolved drug, and the rate of dissolution of dispersed drug particles. Equations in the water-rich phase are also of the diffusion-reaction type. Transport parameters in the polymer-rich phase are coupled to the ternary thermodynamics through friction formalism, and remaining parameters are estimated from literature data, leaving two free parameters: volume fraction of water-rich phase (epsilon) and k, the mass-transfer coefficient for bath-side transfer of the protein. Variations of these parameters lead to predictions of release profiles that vary from a rapid, burst-like behavior followed by a locking-in of the polymer-rich phase, to a uniform, zero-order profile. Comparisons are made to lysozyme release data for three systems: PLGA solutions in N-methlypyrollidinone (NMP), PLA solutions in NMP, and the latter with added Pluronic. Good agreement between model predictions and data is shown; in particular, the transition from rapid release to zero-order kinetics that occurs on addition of Pluronic is illustrated.
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PMID:A model for drug release from fast phase inverting injectable solutions. 1565 41

Poly(lactic acid) (PLA) was successfully grafted to both ends of Pluronic F127 block copolymers (PEO-PPO-PEO) to obtain amphiphilic PLA-F127-PLA block copolymers. The block composition and structure of PLA-F127-PLA block copolymers were studied by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), differential scanning calorimetric (DSC) and wide angle X-ray diffraction (WXRD) techniques. Data from DSC and WXRD measurements indicated that Tg and Tm of PLA blocks in PLA-F127-PLA block polymers are lower than those of PLA homopolymer. Furthermore, Tm and crystallinity of PLA blocks decrease with decreasing PLA block length in PLA-F127-PLA block copolymers. The release behaviors of both hydrophobic 9-(methylaminomethyl)anthracene (MAMA) and hydrophilic procaine hydrochloride (PrHy) model drugs from PLA-F127-PLA nanoparticles with vesicular structure in PBS solution at 37 degrees C were examined by UV spectroscopy. The release kinetics of both MAMA and PrHy model drugs from PLA-F127-PLA nanoparticles exhibit burst release characteristics, which are believed to be controlled by concentration gradient resulting from the slow hydrolytic degradation of PLA segments.
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PMID:Release kinetics of hydrophobic and hydrophilic model drugs from pluronic F127/poly(lactic acid) nanoparticles. 1571 May 1

The contrast variation technique in small angle neutron scattering (SANS) was used to investigate the inner structure of nanocapsules on the example of poly(D,L-lactide) (PLA) nanocapsules. The determination of the PLA and Poloxamer shell thickness was the focus of this study. Highest sensitivity on the inner structure of the nanocapsules was obtained when the scattering length density of the solvent was varied between the one of the Miglyol core and the PLA shell. According to the fit data the PLA shell thickness was 9.8 nm. The z-averaged radius determined by SANS experiments correlated well with dynamic light scattering (DLS) results, although DLS values were systematically slightly higher than the ones measured by SANS. This could be explained by taking into account the influence of Poloxamer attached to the nanocapsules surface. For a refined fit model with a second shell consisting of Poloxamer, SANS values and DLS values fitted well with each other. The characterization method presented here is significant because detailed insights into the nanocapsule and the Poloxamer shell were gained for the first time. This method could be used to develop strategies for the optimization of the shell properties concerning controlled release and to study changes in the shell structure during degradation processes.
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PMID:Core-shell structure of Miglyol/poly(D,L-lactide)/Poloxamer nanocapsules studied by small-angle neutron scattering. 1600 99

Poly(lactic acid) (PLA) was successfully grafted to both ends of Pluronic F127 block copolymer (PEO-PPO-PEO) to obtain amphiphilic PLA-F127-PLA block copolymers. The effect of enzymatic degradation on the release behaviors of hydrophobic model drug 9-(methylaminomethyl)anthracene (MAMA) from PLA-F127-PLA nano-particles with vesicular structure was studied by UV-Vis spectroscopy. It was observed that the release rate of MAMA from PLA-F127-PLA nano-particles with the enzymatic degradation varied with temperature due to the activity of the enzyme with temperature. However, the enzyme concentration has negligible effect on the release rates of MAMA.
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PMID:Effect of enzymatic degradation on the release kinetics of model drug from Pluronic F127/poly(lactic acid) nano-particles. 1619 6


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