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)

The aim of the present study was to evaluate the cellular interaction of nanoparticles (NPs) prepared from different pegylated polymers and elucidate the effect of polymer architecture, for instance, grafted versus block copolymer on their cellular uptake. Fluorescein-labeled NPs of four different polymers, viz., poly(D,L-lactide) (PLA), poly(ethylene glycol)(1%)-graft-poly(D,L-lactide) (PEG(1%)-g-PLA), poly(ethylene glycol)(5%)-graft-poly(D,L-lactide) (PEG(5%)-g-PLA), and (poly(D,L-lactide)-block-poly(ethylene glycol)-block-poly(D,L-lactide))(n) multiblock copolymer (PLA-PEG-PLA)(n) were prepared. These NPs were characterized for their size, zeta-potential, and surface morphology. XPS studies revealed possibility of chemical interaction between PLA-COOH groups and PVA-OH groups, thus making it difficult to be washed off the NP surface completely. Grafted polymer NPs showed more surface PEG coverage than (PLA-PEG-PLA)(n) despite of their comparatively lower PEG content. The results of surface properties were translated into protein binding showing least amount of proteins bound to grafted copolymer NPs as against multiblock copolymer NPs. NPs showed no toxicity to RAW 264.7 cells. Cellular uptake of NPs was temperature and concentration-dependent as well as involved clathrin-mediated processes. Thus, this study confirms the importance of polymer architecture in determining the surface properties and hence, protein binding and cellular interactions of NPs. Also, it was shown that grafted copolymer NPs reduced macrophage uptake as compared to multiblock copolymer although mechanisms different than phagocytosis were involved.
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PMID:Effect of polymer architecture on surface properties, plasma protein adsorption, and cellular interactions of pegylated nanoparticles. 1822 49

This study presents a simple method for the fabrication of an orthogonal surface that can be applied for cell patterning without the need to immobilize specific adhesive peptides, proteins, or extracellular matrix (ECM) for cell attachment. Micromolding in capillaries (MIMIC) produced two distinctive regions. One region contained poly(ethylene glycol)-poly(D,L-lactide) diblock copolymer (PEG-PLA) designed to provide a biological barrier to the nonspecific binding of proteins and fibroblast cells. The other region was coated with polyelectrolyte (PEL) to promote the adhesion of biomolecules including proteins and cells. Resistance to the adsorption of proteins increased with the length of PEG and PLA chains because the longer PEG chain increased the PEG layer thickness and the longer PLA chain induced stronger interaction with the PEL surface. The PEG5k-PLA2.5k (20mg/ml) was the most efficient candidate for the prevention of protein adhesion among the PEG-PLA copolymers examined. The orthogonal functionality of prepared surfaces having PEL regions and background PEG-PLA regions resulted in rapid patterning of biomolecules. Fluorescein isothiocyanate-tagged bovine serum albumin (FITC-BSA) and fibroblast cells successfully adhered to the exposed PEL surfaces. Although methods for cell patterning generally require an adhesive protein layer on the desired area, these fabricated surfaces without adhesive proteins provide a gentle microenvironment for cells. In addition, our proposed approach could easily control patterns, sizes, and shapes at micron scale.
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PMID:Preparation of orthogonally functionalized surface using micromolding in capillaries technique for the control of cellular adhesion. 1830 84

Three-layered milli-capsules (3LMC), diameter of 1.85+/-0.07 and 0.15+/-0.09 mm thickness, were designed for the long-term subcutaneous (sc) administration of drugs. 3LMCs composed of (1) surface membrane (release rate control membrane), (2) drug-carrying layer and (3) base membrane were prepared by dispensing each solution in series. As surface membrane, poly-(epsilon-caprolactone) having MW of 70 kDa (PCL70) was used in combination with plasticizer, polysorbate 60 (Tween60). Base membrane was prepared with PCL70. Fluorescein isothiocyanate labeled dextrans (FD-4, MW=4 kDa and FD-20, MW=20 kDa) were used as model drug and in vitro release experiment was performed with PCL70 surface membrane containing Tween60 with 0.3, 1.0 and 3.0% (w/w). As the amount of Tween60 increased, release rate of FD-4 was increased. PCL70+0.3% Tween60 membrane showed a good sustained release property for 5 weeks; 50.3+/-6.0% of FD-4 was released during 5 weeks. When FD-20 was encapsulated, long-term sustained release was not obtained, 10.7+/-3.6% was released during 5 weeks. However, when lower MW drug, leuprolide acetate, was encapsulated, 3LMC composed of PCL70+0.3% Tween60 showed a good sustained release property, 63.0+/-5.9% released for 5 weeks. Leuprolide acetate encapsulated 3LMC was evaluated in rat experiment. After sc administration to rats, 0.5 and 1.0 mg, plasma leuprolide concentration showed its maximum concentration at day 1, thereafter gradually decreased and maintained the effective concentration for 14 weeks. Plasma leuprolide concentration vs. time curve showed a good dose-dependency. When surface membrane prepared by blending PCL70 and poly(lactic acid) (PLA) in the molar ratio of 5:1 was used, long-term sustained release property was not obtained. Instead, lower MW PCL, PCL40, was blended with PLA (5:1) to prepare surface membrane, sustained release of leuprolide was observed for 5 weeks. Through those studies, 3LMC has been shown to be a long-term sustained release preparation by properly selecting the surface membrane.
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PMID:Three-layered microcapsules as a long-term sustained release injection preparation. 1978 37

One of the therapeutics for acute cerebral ischemia is tissue plasminogen activator (t-PA). Using t-PA after 3 hour time window increases the chances of hemorrhage, involving multiple mechanisms. In order to show possible mechanisms of t-PA toxicity and the effect of the free radical scavenger edaravone, we administered vehicle, plasmin, and t-PA into intact rat cortex, and edaravone intravenously. Plasmin and t-PA damaged rat brain with the most prominent injury in t-PA group on 4-HNE, HEL, and 8-OHdG immunostainings. Such brain damage was strongly decreased in t-PA plus edaravone group. For the neurovascular unit immunostainings, occludin and collagen IV expression was decreased in single plasmin or t-PA group, which was recovered in t-PA plus edaravone group. In contrast, matrix metalloproteinase-9 intensity was the strongest in t-PA group, less in plasmin, and was the least prominent in t-PA plus edaravone group. In vitro data showed a strong damage to tight junctions for occludin and claudin 5 in both administration groups, while there were no changes for endothelial (NAGO) and perivascular (GFAP) stainings. Such damage to tight junctions was recovered in t-PA plus edaravone group with similar recovery in Sodium-Fluorescein permeability assay. Administration of t-PA caused oxidative stress damage to lipids, proteins and DNA, and led to disruption of outer parts of neurovascular unit, greater than the effect in plasmin administration. Additive edaravone ameliorated such an oxidative damage by t-PA with protecting outer layers of blood-brain barrier (in vivo) and tight junctions (in vitro).
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PMID:Free radical scavenger edaravone administration protects against tissue plasminogen activator induced oxidative stress and blood brain barrier damage. 2085 48