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

A series of PEO/PLA copolymers, covering a wide range of compositions and segmental lengths, was synthesized, and their morphology was investigated by means of DSC and IR studies. For matrices comprising PEO chains with molecular weights below 3400, no soft-segment crystallinity was detected. When long hard segments were present, essentially monophasic, semicrystalline polymers were obtained, with PLA blocks melting around 130 degrees C. Polymers containing longer soft segments (PEO 6000) exhibited a two-phase matrix, with both components being able to crystallize. The relative degree of crystallinity of PEO and PLA blocks was also determined. The thermal history of the sample strongly affected the morphology of the matrix, especially when both blocks were long enough to crystallize. To further explore these polymers, solvent cast films were prepared and their morphology assessed. Casting from acetone, which is an excellent solvent for PLA, resulted in hard blocks exhibiting lower degrees of crystallinity, while methanol had a similar effect on PEO soft segments.
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PMID:Morphological study of biodegradable PEO/PLA block copolymers. 368 Mar 15

The rapid uptake of injected nanoparticles by cells of the mononuclear phagocytes system (MPS) is a major obstacle when a long blood circulation time is needed. Whereas nanoparticles made from PLA and stabilized by surfactants (PLA-F68) are rapidly phagocytized, the rate of phagocytosis is strongly reduced in case of nanoparticles made from a diblock copolymer (PLA-PEO). Because of the role of the complement system in opsonization, this difference of phagocytosis was hypothesized to be related to this system. An important complement consumption was obtained in 5 min in the presence of PLA-F68 particles. In the presence of a higher surface area of PLA-PEO particles possessing a high PEO surface density, the consumption remained very low. When the average PEO surface density was decreased on such particles below a given threshold, a fast and strong complement consumption occurred again. These experimental data support the concept of steric repulsion towards proteins, by surfaces covered with terminally attached PEO chains and emphasize the prime importance of PEO surface density in such an effect. The major, but probably not exclusive, role of complement as an opsonin capable of inducing a fast phagocytosis by MPS should be taken into account concerning the in vitro evaluation of nanoparticles as candidates for a long blood circulation.
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PMID:Effect of PEO surface density on long-circulating PLA-PEO nanoparticles which are very low complement activators. 884 61

When surfactant-stabilized biodegradable poly(lactic acid) (PLA) particles are injected into rats, the rate of clearance from blood is fast. The rate can be strongly reduced by using particles made from diblock copolymers of PLA and poly(ethylene oxide) (PLA-PEO), resulting in an increased duration of contact with the components of the coagulation system. Thus, possible adverse effects such as activation of the coagulation cascade could occur. In this paper, the interactions of surfactant-stabilized PLA and PLA-PEO nanoparticle suspensions with the plasma factors of the coagulation system are presented. PLA suspensions stabilized by sodium cholate (PLA-Ch) interact with thrombin, factor V and calcium ions. Formation of complexes and aggregates is induced by addition of calcium ions to PLA-Ch suspensions in the presence or in the absence of plasma. On the contrary, PLA-PEO suspensions are remarkably inert towards the coagulation factors and calcium ions, even when cholate is present. Steric repulsion owing to the high surface density of PEO is sufficient to avoid strong interations with the proteins and formation of aggregates between particles.
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PMID:Interactions of poly(lactic acid) and poly(lactic acid-co-ethylene oxide) nanoparticles with the plasma factors of the coagulation system. 906 88

Regeneration of organizationally complex tissue requires regulation of spatial distributions of particular cell types in three dimensions. In this paper we demonstrate an integration of polymer processing and selective polymer surface modification using methods suitable for construction of three-dimensional polymer scaffolds which may aid such cell organization. Specifically, the surfaces of degradable polyesters were modified with poly(ethylene-oxide) (PEO)-poly(propylene-oxide) (PPO) copolymers using a process compatible with a solid free-form fabrication technique, the 3DP printing process. We demonstrate inhibition of cell (hepatocyte and fibroblast) adhesion to regions of two-dimensional poly(lactide) (PLA) substrates modified with PEO-PPO-PEO copolymers. We further show that PEO-PPO-PEO-modified surfaces which are not adhesive for hepatocytes or fibroblasts can be made selectively adhesive for hepatocytes by covalent linkage of a carbohydrate ligand specific for the hepatocyte asialoglycoprotein receptor to the PEO chain ends. Our approach may be generally useful for creating regionally selective, microarchitectured scaffolds fabricated from biodegradable polymers, for spatial organization of diverse cell types.
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PMID:Integration of surface modification and 3D fabrication techniques to prepare patterned poly(L-lactide) substrates allowing regionally selective cell adhesion. 949 39

Nanoparticles with either physically adsorbed or covalently bound poly(ethylene oxide) (PEO) coatings were produced from various combinations of poly(lactic acid) (PLA) and diblock or triblock copolymers of PLA and PEO. The particles were produced by the salting-out process and purified by the cross-flow filtration technique. The amount of PEO at the nanoparticle surface, as well as the residual amount of emulsifier poly(vinyl alcohol) were assessed, with a good correlation with expected values. Stability of the nanoparticulate suspensions was studied at 4 degrees C and after freezing under various conditions for up to 6 months. The nanoparticle redispersibility after storage was related to the thermal behavior of the PEO coatings. The in vitro cellular uptake of the different types of nanoparticles was compared by flow cytometry after incubation with human monocytes in serum and in plasma. The influence of the PEO molecular weight and surface density on the particle uptake was especially marked for the diblock and triblock copolymer formulations, with a decrease in uptake of up to 65% with one of the diblock copolymer formulations. Nanoparticles made of triblock copolymer with short PEO chains at their surface in the postulated "loop conformation" proved to be as resistant to cellular uptake as nanoparticles made of diblock copolymers with PEO chains in the "brush conformation".
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PMID:Cellular uptake of PEO surface-modified nanoparticles: evaluation of nanoparticles made of PLA:PEO diblock and triblock copolymers. 1093 24

In this study, the formulation and process parameters that determine successful production and long-term stability of freeze-dried poly(lactic acid) (PLA) nanoparticles with "hairy-like" poly(ethylene oxide) (PEO) surfaces were investigated. Nanoparticles with grafted (covalently bound) PEO coatings were produced by the salting-out method from blends of PLA and PLA-PEO diblock or triblock copolymers. PLA nanoparticles with physically adsorbed PEO were also produced. The redispersibility of the nanoparticles after freeze-drying under various conditions was assessed. The surface of the nanoparticles was characterized and classified in terms of "brush" and "loop" conformations. Upon freeze-drying, it appeared that the presence of PEO at the nanoparticle surface could severely impair the redispersibility of the particles, especially in the PEO-grafted systems. This effect was shown to be related to the amount and molecular weight of PEO in the various formulations. In most cases, particle aggregation was prevented by use of trehalose as lyoprotective agent. Increasing the concentration of particles in the suspension to be freeze-dried was shown to induce much less damage to the nanoparticles, and freezing the suspension at a very low temperature (-196 degrees C) was found to further improve the lyoprotective effect. Most of the lyoprotected nanoparticles remained stable for at least 12 weeks at 4 and -25 degrees C. The production and preservation of freeze-dried PLA-PEO diblock and triblock copolymer nanoparticles is feasible under optimized lyoprotective conditions.
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PMID:Freeze-drying and lyopreservation of diblock and triblock poly(lactic acid)-poly(ethylene oxide) (PLA-PEO) copolymer nanoparticles. 1110 47

A series of PLA/PEO/PLA triblock copolymers was prepared by ring opening polymerization of rac-lactide in the presence of various di-hydroxyl poly (ethylene glycol)s, using CaH2 as a biocompatible initiator. Hydrogels were prepared by a phase separation method consisting of introducing small amounts of water over solutions of the copolymers in a biocompatible organic solvent, namely tetraglycol [poly(ethylene glycol monotetrahydrofurfuryl ether)]. The resulting hydrogels appeared much more hydrophilic than the rather tough hydrogels formed by swelling of dry tablets or films processed from the same copolymers. The phase separation-derived hydrogels were soft enough to be injected through a trochar. Two proteins, namely bovine serum albumine (BSA) and fibrinogen, were physically entrapped in these hydrogels by mixing with the polymer solutions before gel formation. This procedure appeared to be protein-respecting according to circular dichroism analysis on the released BSA. Dramatically different release profiles were obtained for the two proteins. In the case of BSA, the release depended on the quantity of protein incorporated in the hydrogel and presented a parabolic-type profile, in agreement with the behaviors of diffusion-controlled monolitic drug delivery devices. In contrast, almost linear release profiles were observed in the case of fibrinogen, the hydrogels behaving like a reservoir drug delivery system. These findings are tentatively interpreted in terms of gel-protein compatibility in the case of BSA and gel-protein incompatibility in the case of fibrinogen.
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PMID:Protein release from physically crosslinked hydrogels of the PLA/PEO/PLA triblock copolymer-type. 1120 40

The PLA-b-PEO block copolymers were studied as potential carriers for anti-inflammatory and anticancer drugs. The copolymers were labeled with 125I, and their micelles in physiological saline were prepared by dialysis. Copolymer 1, with Mw = 12,360 (PLA/PEO = 7000/5000), formed particles of about 300 nm in diameter (Rh was 150 nm), whereas copolymer 2, with Mw = 20,470 (6000/14,000), made up micelles of about 72 nm in diameter (Rh was 35.8 nm). Their pharmacokinetic and biodistribution profiles were compared in normal rats and rats with carrageenan-induced inflammation after intravenous application of about 5 mg/kg of each copolymer. Copolymer 2, forming smaller particles, showed longer distribution and elimination half-lives. Both copolymers under study exhibited significantly higher uptake by inflammatory tissue compared with noninflammatory one. The study indicates that PLA-b-PEO copolymers, having different molecular weight of the chains, have similar biological behavior in most organs and tissues. Differences in the uptake by some organs (mainly kidney and bowels) and in activity level in blood at later time intervals were found. Significantly different clearance values are due to different ratios of hydrophobic and hydrophilic chains of the copolymers.
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PMID:Pharmacokinetics and distribution of 125I-PLA-b-PEO block copolymers in rats. 1276 May 66

Biodegradable materials based on polymers of hydroxy acids are studied for application in artificial vascular substitutes. Polymers with functional surfaces are being developed, carrying specific recognition structures to affect selectively the adhesion and proliferation of endothelial cells (EC) and vascular smooth muscle cells (VSMC). This preliminary study focuses on evaluation of adhesion and growth of VSMC on surfaces of polylactide polymers and those modified by amphiphilic polylactide/poly(ethylene oxide) copolymers. Poly(L-lactic acid), PLLA, and poly(DL-lactic acid), PDLLA, and a block copolymer of lactide with a carboxylated poly(ethylene oxide) segment, PLLA-b-PEO-COOH, were synthesized by controlled polymerization of L and D,L-lactide, respectively, and using delta-hydroxy-Z-carboxymethyl-PEO as a macroinitiator for the copolymer. Films of polymers were deposited on glass coverslips by a spin-coating method. Uncoated glass coverslips and Falcon dishes were used as control substrates. VSMC were obtained from the thoracic aorta of young adult male Wistar rats by explantation method and seeded in Dulbecco-Modified Eagle MEM with 10% foetal bovine serum. The number of adhering cells, their shape, size of cell-material contact area and cell population doubling time were evaluated from day 1 to 7 after seeding. It was found that both PLLA and especially PDLLA relatively well supported adhesion and growth of VSMC. However, on carboxylated surfaces of the PLLA-b-PEO-COOH copolymer, a lower number of initially adhering cells (by 37% than on Falcon dishes, pdelta0.05), smaller cell spreading area (by 45% and 37% than on glass and Falcon dishes, respectively, pdelta0.01) and longer doubling time (by 49% and 31% than on glass and Falcon dishes, pdelta0.001). Thus, surfaces coated by a PLA/PEO-COOH copolymer can be used as minimum background surface to reveal the effect of other more specific adhesion structures.
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PMID:Adhesion and growth of rat aortic smooth muscle cells on lactide-based polymers. 1290 20

The poly(ethylene oxide)-poly(lactide) (PEO-PLA) block copolymers containing a small quantity of carboxylic acid in the PLA block were synthesized. The microscopic characteristics of nanoparticles with carboxylic acid content in the copolymer were analyzed, and the effect of specific interactions between the copolymer and the model drug on the drug loading capacity and the release behavior were investigated systematically. The sizes of nanoparticles prepared by a dialysis method are within the range of 30-40 nm. The nanoparticles prepared from functionalized block copolymers have a very low critical micelle concentration (CMC) value as low as approximately 10(-3) mg/ml, which indicates a good stability of the nanoparticles in spite of the presence of carboxylic acid. The drug loading efficiency of nanoparticles dramatically increased when carboxylic acid content was increased in the block copolymer. This result may be attributed to the increase of interactions between the copolymer and the drug. The release rate of the drug was much slower from nanoparticles containing higher amounts of carboxylic acid in the copolymer, which might be associated with the enhanced interaction between the carboxylic group of copolymers and the drug. These experimental results suggest that the nanoparticles prepared from functionalized PEO-PLA block copolymers could be a good candidate for an injectable drug delivery carrier.
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PMID:Incorporation and release behavior of hydrophobic drug in functionalized poly(D,L-lactide)-block-poly(ethylene oxide) micelles. 1474 84


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