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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Nanoparticles possessing poly(ethylene glycol) (PEG) chains on their surface have been described as blood persistent drug delivery system with potential applications for intravenous drug administration. Considering the importance of protein interactions with injected colloidal dug carriers with regard to their in vivo fate, we analysed plasma protein adsorption onto biodegradable PEG-coated poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(varepsilon-caprolactone) (PCL) nanoparticles employing two-dimensional gel electrophoresis (2-D PAGE). A series of corona/core nanoparticles of sizes 160-270 nm were prepared from diblock PEG-PLA, PEG-PLGA and PEG-PCL and from PEG-PLA:PLA blends. The PEG Mw was varied from 2000-20000 g/mole and the particles were prepared using different PEG contents. It was thus possible to study the influence of the PEG corona thickness and density, as well as the influence of the nature of the core (PLA, PLGA or PCL), on the competitive plasma protein adsorption, zeta potential and particle uptake by polymorphonuclear (PMN) cells. 2-D PAGE studies showed that plasma protein adsorption on PEG-coated PLA nanospheres strongly depends on the PEG molecular weight (Mw) (i.e. PEG chain length at the particle surface) as well as on the PEG content in the particles (i.e. PEG chain density at the surface of the particles). Whatever the thickness or the density of the corona, the qualitative composition of the plasma protein adsorption patterns was very similar, showing that adsorption was governed by interaction with a PLA surface protected more or less by PEG chains. The main spots on the gels were albumin, fibrinogen, IgG, Ig light chains, and the apolipoproteins apoA-I and apoE. For particles made of PEG-PLA45K with different PEG Mw, a maximal reduction in protein adsorption was found for a PEG Mw of 5000 g/mole. For nanospheres differing in their PEG content from 0.5 to 20 wt %, a PEG content between 2 and 5 wt % was determined as a threshold value for optimal protein resistance. When increasing the PEG content in the nanoparticles above 5 wt % no further reduction in protein adsorption was achieved. Phagocytosis by PMN studied using chemiluminescence and zeta potential data agreed well with these findings: the same PEG surface density threshold was found to ensure simultaneously efficient steric stabilization and to avoid the uptake by PMN cells. Supposing all the PEG chains migrate to the surface, this would correspond to a distance of about 1.5 nm between two terminally attached PEG chains in the covering 'brush'. Particles from PEG5K-PLA45K, PEG5K-PLGA45K and PEG5K-PCL45K copolymers enabled to study the influence of the core on plasma protein adsorption, all other parameters (corona thickness and density) being kept constant. Adsorption patterns were in good qualitative agreement with each other. Only a few protein species were exclusively present just on one type of nanoparticle. However, the extent of proteins adsorbed differed in a large extent from one particle to another. In vivo studies could help elucidating the role of the type and amount of proteins adsorbed on the fate of the nanoparticles after intraveinous administration, as a function of the nature of their core. These results could be useful in the design of long circulating intravenously injectable biodegradable drug carriers endowed with protein resistant properties and low phagocytic uptake.
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PMID:'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. 1091 52

The calcium-dependent cross-linking enzyme tissue transglutaminase (tTgase, type II) is a potential novel player at the cell surface, where its contribution to cell adhesion and stabilization of the extracellular matrix is becoming increasingly recognized. We investigated whether tTgase enhances the biological recognition of poly (DL lactide co-glycolide) (PLG), poly (epsilon-caprolactone) (PCL), and poly (L lactide) (PLA), biomaterials widely used in medical implants. Three cell-model systems consisting of human osteoblasts, endothelial cells (ECV-304), and Swiss 3T3 fibroblasts were utilized, in which tTgase expression was modulated by gene transfer, and the ability of cells to spread on these polymers was quantified in relation to the altered level of expressed tTGase. Results show that over-expression of tTgase in human osteoblasts positively correlated with cell spreading on PLG, while no attachment and spreading was found on PCL and PLA. Antisense silencing of tTgase in the endothelial cells led to a marked reduction of cell spreading on all polymers. The hydrophobic nature of PLC also appeared to favor endothelial cell attachment. Spreading of Swiss 3T3 fibroblasts on these biomaterials was only slightly affected by increased expression of tTgase, although cell spreading on control glass was increased. We propose that the consideration of tTgase-mediated bioactivity in novel biomaterials may improve cell attachment and promote biocompatibility.
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PMID:Role of the cross-linking enzyme tissue transglutaminase in the biological recognition of synthetic biodegradable polymers. 1109 90

Biodegradable polymer/hydroxyapatite (HA) composites have potential application as bone graft substitutes. Thin films of polymer/HA composites were produced, and the initial attachment of primary human osteoblasts (HOBs) was assessed to investigate the biocompatibility of the materials. Poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLA) were used as matrix materials for two types of HA particles, 50-microm sintered and submicron nonsintered. Using ESEM, cell morphology on the surfaces of samples was investigated after 90 min, 4 h, and 24 h of cell culture. Cell activity and viability were assessed after 24 h of cell culture using Alamar blue and DNA assays. Surface morphology of the polymer/HA composites and HA exposure were investigated using ESEM and EDXA, respectively. ESEM enabled investigation of both cell and material surface morphology in the hydrated condition. Combined with EDXA it permitted chemical and visual examination of the composite. Differences in HA exposure were observed on the different composite surfaces that affected the morphology of attached cells. In the first 4 h of cell culture, the cells were spread to a higher degree on exposed HA regions of the composites and on PLA than they were on PCL. After 24 h the cells were spread equally on all the samples. The cell activity after 24 h was significantly higher on the polymer/HA composites than on the polymer films. There was no significant difference in the activity of the cells on the various composite materials. However, cells on PCL showed higher activity compared to those on PLA. A polymer surface exhibiting "point exposure" of HA appeared to provide a novel and favorable substrate for primary cell attachment. The cell morphology and activity results indicate a favorable cell/material interaction and suggest that PLA and PCL and their composites with HA may be candidate materials for the reconstruction of bony tissue. Further investigations regarding long-term biomaterial/cell interactions and the effects of acidic degradation products from the biodegradable polymers are required to confirm their utility.
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PMID:Biodegradable polymer/hydroxyapatite composites: surface analysis and initial attachment of human osteoblasts. 1128 75

With this tissue engineering (TE) technique, the peripheral pulmonary artery was successfully reconstructed, using the patient's own venous cells in a 4-year-old girl, 2 years after Fontan procedure. A 4-year-old girl was given a diagnosis of single right ventricle, double-outlet right ventricle and pulmonary atresia. She underwent left modified Blalock-Taussig shunt at a month old, pulmonary artery angioplasty at a year and 3 months old, and bidirectional cavopulmonary shunt at 2 years and a month old. She underwent again pulmonary artery angioplasty and Fontan operation at 3 years and 3 months. An angiographical examination 7 months after the operation revealed total occlusion of the right intermediate pulmonary artery. TE technique using autologous cells was indicated. The application of this procedure was approved by the ethical committee in Tokyo Women's Medical University. The patient's parents were thoroughly informed and signed a consent form. Approximately 2 cm of the peripheral vein was explanted under sterile conditions. The tissue was minced, placed in tissue culture dishes and cultured at 37 degrees C, 100% humidity and a 5% CO2 atmosphere for almost a month. The number of cells substantially increased to reach 12 millions for almost a month. The culture medium was changed every 3 days. The polymer tube that served as a scaffold for cells was composed of the copolymer of PCL-PLA (50:50) with reinforcement by woven PGA. The polymer conduit, 10 mm in diameter, 20 mm in length and 1 mm in thickness, was designated to biodegradate within 8 weeks. The number of seeded cells was approximately a million/cm2. The graft transplantation was performed 10 days after seeding cells. The occlusive right intermediate pulmonary artery was reconstructed with the TE vessel graft under extracorporeal circulation with a pump-oxygenator. The patient followed a satisfactory postoperative course. The postoperative angiography demonstrated that the graft was not constricted and dilated but that it preserved good patency. Long-term follow-up are necessary. We plan to continue to use the TE technique using autologous cells in the low pressure system like venous or pulmonary circulation. Because our results even in early experimental phase were valuable and promising, we believe that the TE approach may play an important role in the near future as an another alternative, together with transplantation and artificial organ, especially in the field of cardiovascular surgery that mostly needs replants.
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PMID:[First successful clinical application of tissue engineered blood vessel]. 1199 17

The synthesis of a series of polymeric Eu(III) complexes with polyester ligands, along with supporting emission spectra, luminescence lifetimes, and, for a Eu block copolymer film, atomic force microscopy (AFM) data, is presented. Dibenzoylmethane was derivatized with a hydroxyl initiator site (dbmOH, 1) for tin octoate catalyzed ring opening polymerization of dl-lactide. The resulting poly(lactic acid) macroligand, dbmPLA (2), was combined with EuCl3 to generate Eu(dbmPLA)3 (3). Chelation of both dbmPLA and a polycaprolactone-functionalized bipyridine ligand (bpyPCL2) led to the Eu(III)-centered heteroarm star Eu(dbmPLA)3(bpyPCL2) (4). Unpolarized emission spectra and luminescence lifetimes were recorded for the Eu polymers in CH2Cl2 and for Eu(dbmPLA)3, as a film. Solution data for Eu(dbm)3 and Eu(dbm)3(bpy) were collected for comparison. For Eu tris(dbm) complexes, data were fit to a double exponential decay, indicating the presence of multiple species. Relative amounts of the longer lifetime component increase in the series Eu(dbm)3 solutions to Eu(dbmPLA)3 solutions to Eu(dbmPLA)3 films, perhaps suggesting benefits of the "polymer shell effect" and the diminishment of aquo adducts known to shorten lifetimes. As with the nonpolymeric analogue, data for Eu(dbmPLA)3(bpyPCL2) fit to a single-exponential decay. The sharpness of the feature at 579.7 nm, attributable to the 5D0 --> 7F0 transition in the emission spectrum of 4, lends further support for a homogeneous sample. AFM studies of "as cast" thin films of 4 reveal a lamellar structure with a 17.5 nm repeat. These microstructures, inferred to contain Eu luminophores at the glassy PLA-crystalline PCL domain interfaces, are modified by thermal treatment.
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PMID:Site-isolated luminescent europium complexes with polyester macroligands: metal-centered heteroarm stars and nanoscale assemblies with labile block junctions. 1212 Oct 83

The miscibility and phase behavior of two stereoisomer forms of poly(lactide) (PLA: poly (L-lactide) (PLLA) and poly(DL-lactide) (PDLLA)) blends with poly(epsilon-caprolactone)-b-poly(ethylene glycol) (PCL-b-PEG) and PCL-b-monomethoxy-PEG (PCL-b-MPEG) block copolymers have been investigated by differential scanning calorimetry (DSC). The DSC thermal behavior of both the blend systems revealed that PLA is miscible with the PEG segment phase of PCL-b-(M)PEG but is still immiscible with its PCL segment phase although PCL was block-copolymerized with PEG. On the basis of these results, PCL-b-PEG was added as a compatibilizer to PLA/PCL binary blends. The improvement in mechanical properties of PLA/PCL blends was achieved as anticipated upon the addition of PCL-b-PEG. In addition, atomic force microscopy (AFM) measurements have been performed in order to study the compositional synergism to be observed in mechanical tests. AFM observations of the morphological dependency on blend composition indicate that PLA/PCL blends are immiscible but compatible to some extent and that synergism of compatibilizing may be maximized in the compositional blend ratio before apparent phase separation and coarsening.
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PMID:Compatibilization effect of poly(epsilon-caprolactone)-b-poly(ethylene glycol) block copolymers and phase morphology analysis in immiscible poly(lactide)/poly(epsilon-caprolactone) blends. 1242 54

Commercial lipases were examined for their degradation efficiency of aliphatic polyester films. In 100 days immersion of polyester films in lipase solutions at 37 degrees C at pH 7.0, Lipase Asahi derived from Chromobacterium viscosum degraded polybutylene succinate-co-adipate (PBSA), poly (e-caprolactone) (PCL) and polybutylene succinate (PBS), and Lipase F derived from Rhizopus niveus degraded PBSA and PCL during 4-17 days. Lipase F-AP15 derived from Rhizopus orizae could degrade PBSA in 22 days. In these cases, PBS and PBSA were mainly degraded to dimers, whereas PCL was mainly degraded to monomers. Only poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/V) and poly (L-lactide) (PLA) were not degraded in the experiments. However, PLA degraded completely at 55 degrees C, pH 8.5 with Lipase PL during 20 days. This result could be explained with the sequential reactions of the chemical hydrolysis of the polymer to oligomers at higher pH and temperature, and the succeeding enzymatic hydrolysis of oligomers to the monomers.
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PMID:Degradation of aliphatic polyester films by commercially available lipases with special reference to rapid and complete degradation of poly(L-lactide) film by lipase PL derived from Alcaligenes sp. 1244 16

Various ABA-type tri-block copolymers composed of poly(L-lactide) (PLA) or poly (lactide-co-glycolide) (PLGA) as the side A block and poly(epsilon-caprolactone) (PCL) as the middle B block were synthesized to produce rapidly degrading elastic matrices useful for tissue engineering scaffolds. The terminal di-hydroxyl groups in PCL-diol (MW 2000) were used as the initiator for the ring-opening polymerization of L-lactide or D,L-lactide and glycolide, employing stannous octoate as a catalyst. A series of copolymers were synthesized by varying the chain length and monomer composition of the PLA (PLGA) block, while the chain length of the PCL block was fixed. It was found that PLGA/PCL/PLGA copolymers with a MW of 10000 and lactide/glycolide ratios of 50/50 and 75/25 demonstrated desirable mechanical properties of elasticity (Young's modulus 26.0 and 19.8 MPa) and showed controllable degradability over a 2-month period depending on the monomer composition.
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PMID:Synthesis and characterization of elastic PLGA/PCL/PLGA tri-block copolymers. 1248 91

The design of surface-engineered nanoparticles for targeting to specific sites is a major challenge. To our knowledge, no study in the literature deals with ligand functionalization of biodegradable nanoparticles through biotin-avidin interactions. With the aim of conceiving small-sized nanoparticles which can be easily functionalized with a variety of ligands or mixtures thereof, biotinylated and PEGylated biotin-poly(ethylene glycol)-poly(epsilon-caprolactone) (B-PEG-PCL) copolymers were synthesized and used to prepare nanoparticles of around 100 nm. Avidin, followed by biotinylated wheat germ agglutinin as a model lectin, were coupled to their surface by taking advantage of the strong biotin-avidin complex formation. The cytotoxicity of the nanospheres towards Caco-2 cells in culture was negligible (more than 82% cell survival for nanoparticle concentrations up to 300 microg/well). The amount of radiolabeled poly(lactic acid) (PLA) or PEG-PLA nanoparticles associated with Caco-2 cells was only 0.7% and 1.5% of the amount added, respectively. This value was increased to 8.5% when a sufficient amount of lectin was bound to the PEG-PLA copolymer. After further studies, the biotin-PEG-coated nanoparticles could be helpful tools for studying the interaction between cells and functionalized nanoparticles with various surface characteristics (PEG layer density and thickness, ligand type and density).
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PMID:Surface-engineered nanoparticles for multiple ligand coupling. 1292 62


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