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

Several types of sugar-installed poly(ethylene glycol)/poly(DL-lactide) (sugar-PEG/PLA) block copolymers were synthesized. The synthesized block copolymer forms a core-shell type polymeric micelle in aqueous media possessing sugar molecules on its surface. Specific recognition of lectin proteins with the sugar molecules on the micelle surface was observed. Both the galactose- and lactose-installed micelles specifically interacted with RCA-1; on the other hand the mannose-installed micelle interacted specifically with Con A. With a lectin-immobilized affinity column, the cluster effect of the sugar molecule on the micelle surface was clearly observed.
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PMID:Sugar-installed block copolymer micelles: their preparation and specific interaction with lectin molecules. 1177 74

A biodegradable and biocompatible polymeric system was developed for the controlled release of vancomycin for the treatment of brain abscesses. Poly(D,L-lactic acid) (PLA) and its copolymers poly(lactide-co-glycolide) PLGA 90:10 and PLGA 70:30, were prepared. Polymer disks containing vancomycin (VN) were prepared by solvent casting from methylene chloride solutions. Degradation of the polymer disk was studied by scanning electron microscopy, NMR and GPC. SEM revealed an increasing degree of degradation with time with both PLGAs, the effect being more distinct in the PLGA with the higher glycolide content (PLGA 70:30), which was confirmed with GPC, which showed both a decrease in the molecular weights of PLGA and a decrease in the heterogeneity index (chain length distribution) upon incubation in isotonic phosphate buffer at 37 degrees C for up to 5 weeks. NMR showed a decrease in the CH2 contents of the copolymers, implying that the glycolide component of the copolymers is being preferentially degraded. In situ, vancomycin release behaviour of the disks in pH 7.4 phosphate buffer saline (PBS) was followed for approximately 2 months in a static system. It was observed that release was according to Higuchi kinetics (Q vs. t(1/2)), and introduction of low molecular weight PLA or hydrophilic compounds like PEG increased the release rate.
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PMID:Vancomycin release from poly(D,L-lactide) and poly(lactide-co-glycolide) disks. 1181 62

The combination of poly(ethylene glycol) (PEG) with a biodegradable poly(ester), such as poly(D,L-lactic acid) (PLA), is an approach that has been successfully used for the stabilization of proteins and peptides in several biodegradable delivery devices. The acylation of peptides inside degrading PLA microspheres has been described only recently as another instability mechanism related to the accumulation of polymer degradation products inside eroding PLA. We investigated whether the block copolymerization of PLA with PEG reduces peptide acylation inside degrading microspheres. Diblock copolymers consisting of poly(D,L-lactic acid) covalently bound to poly(ethylene glycol)-monomethyl ether (Me.PEG-PLA) were used for these investigations. Human atrial natriuretic peptide (ANP) was incorporated into microspheres manufactured from Me.PEG5-PLA45, a diblock copolymer with an overall PEG content of 10%. Peptide integrity inside the microspheres was monitored by HPLC-MS analysis during 4 weeks of microsphere degradation in isotonic phosphate buffer (pH 7.4) at 37 degrees C. Inside the degrading Me.PEG5-PLA45 microspheres, acylation products as well as an oxidation product of ANP were formed. The results demonstrate that the combination of PEG with PLA does not necessarily display a favorable effect concerning peptide acylation inside degrading polymer microspheres. However, they also suggested that the acylation reaction is mainly driven by the formation and accumulation of polymer degradation products inside the degrading microspheres.
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PMID:The effect of poly(ethylene glycol)-poly(D,L-lactic acid) diblock copolymers on peptide acylation. 1194 95

Photoreactive phenylazide-end-capped liquid copolymers were prepared by ring-opening copolymerization of epsilon-caprolactone (CL) and trimethylene carbonate (TMC) at an equimolar monomer feed ratio in the presence of a polyol, namely, a low-molecular-weight alcohol (di-, tri-, and tetraol) or poly(ethylene glycol) (PEG) as an initiator and tin(II) 2-ethylhexanoate as a catalyst, followed subsequently by phenylazide derivatization at their hydroxyl terminus. These tri- and tetrabranched liquid copolymers (precursors) with a molecular weight from approximately 2500 to 7000 g/mol were cross-linked to yield insoluble solids by ultraviolet (UV) light irradiation. The photocuring rate increased with increasing functionality of phenylazide and UV intensity and decreasing thickness of the liquid film of precursors. The photo-cross-linkability of phenylazide-derivatized liquid copolymers was found to be higher than that of the corresponding coumarin-derivatized liquid copolymers. Poly(lactide) (PLA) films surface-layered with photocured copolymers were prepared by coating surfaces with phenylazide-derivatized copolymers and their subsequent photoirradiation. Endothelial cells adhered well on the nontreated PLA and low-molecular-weight alcohol-based copolymer-layered and photocured films. Little cell adhesion was observed on the hydrolytically surface-eroded PLA film and the PEG-based copolymer-layered film. When a phenylazide-derivatized hexapeptide with the cell-adhesion tripeptidyl sequence, Arg-Gly-Asp (RGD), common to cell adhesive proteins, was photoimmobilized on these surfaces, the surfaces became cell adhesive. Microarchitectured surfaces, which were prepared by sequential procedures of surface coating and photocuring using a photomask with lattice windows, produced regionally differentiated cell adhesiveness.
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PMID:Liquid, phenylazide-end-capped copolymers of epsilon-caprolactone and trimethylene carbonate: preparation, photocuring characteristics, and surface layering. 1209 9

To develop a new technology that enhances the regeneration potential of bone and the repair of large intercalated defects in long bone, recombinant human bone morphogenetic protein-2 (BMP-2; 20 microg or 40 microg) was mixed in a polymer gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were stabilized by an intramedullary rod. In controls, the titanium fiber-mesh cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after implantation, new bone had formed on the surface of the implant and had bridged the defect. All of the defects (5/5) treated by cylinders containing 120 microg (40 microg x 3) of BMP were repaired completely. New bone formation was also found inside the pores of the cylinders. The defect was not repaired in the control animals. These results demonstrate that these new composite implants fabricated by combining rhBMP, synthetic degradable polymers and compatible biomaterials enhance the regeneration potential of bone. Thus, it is possible that large skeletal defects can be repaired using this prosthesis in lieu of autogenous bone graft.
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PMID:Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer. 1220 36

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

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

Lactose molecules were installed on the surface of poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) block copolymer micelles in the scope of seeking specific recognition by cell surface receptors at hepatic sites. This, in turn, is expected to result in the formation of a complex displaying prolonged retention times and thus enhanced cellular internalization by receptor-mediated endocytosis. The so-obtained particles based on a block copolymer of molecular weight 9400 g/mol (4900/4500 g/mol for the PEG and PLA blocks, respectively) were found to have an average hydrodynamic diameter of 31.8 nm, as measured by dynamic light scattering. Further, the particle size distribution (micro(2)/Gamma(2)) was found to be lower than 0.08. Lactose-PEG-PLA micelles (Lac-micelles) were then injected over a gold surface containing Ricinus communis agglutinin lectins simulating the aforementioned glycoreceptors, and their interaction was studied by surface plasmon resonance. Then, a kinetic evaluation was carried out, by fitting the observed data mathematically. It appears that Lac-micelles bind in a multivalent manner to the lectin protein bed, which logically results in low dissociation constants. Micelles bearing a ligand density of 80% (Lac-micelles 80%: 80 lactose molecules per 100 copolymer chains) exhibit fast association phases (k(a1) = 3.2 x 10(4) M(-)(1) s(-)(1)), but also extremely slow dissociation phases (k(d1) = 1.3 x 10(-)(4) s(-)(1)). Recorded sensorgrams were fitted with a trivalent model, conveying a calculated equilibrium dissociation constant (K(D1) = k(d1)/k(a1)) of about 4 nM. The importance of cooperative binding was also assessed, by preparing Lac-micelles bearing different ligand densities, and by discussing the influence of the latter on kinetic constants. Interestingly enough, whereas Lac-micelles 80% bind in a trivalent manner to the protein bed, Lac-micelles 20% are still capable of forming bivalent complexes with the same protein bed (K(D1) = 1360 nM). Therefore, despite enhanced kinetic values brought about by a supplementary bond, lower ligand densities appear to be more effective on a molecular basis.
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PMID:Lactose-installed poly(ethylene glycol)-poly(d,l-lactide) block copolymer micelles exhibit fast-rate binding and high affinity toward a protein bed simulating a cell surface. A surface plasmon resonance study. 1252 7

Biodegradable polymers, such as poly(lactic acid) (PLA) and poly(lactic-coglycolic acid) (PLGA), are attractive materials for tissue engineering because of their degradative and mechanical properties, which permit scaffolds to be tailored to the individual requirements of different tissues. Although these materials support tissue development, their chemical properties offer no control of cell adhesion or function because their surfaces become immediately masked by adsorbing serum proteins when the materials come into contact with body fluids. Furthermore, adhesion proteins undergo conformational changes and a decrease in bioactivity when adsorbed to hydrophobic materials, such as PLA. To overcome these limitations, we modified the properties of PLA by synthesizing a diblock copolymer with poly(ethylene glycol) (PEG), which is known to reduce the amount of adsorbed proteins and to modify their conformation. By altering the PEG content of these diblock copolymers we were able to control the adsorption of adhesion proteins and, because cell adhesion takes place only in the presence of serum proteins, to control cell adhesion and cell shape. Marrow stromal cell differentiation to the osteoblastic phenotype was strongly improved on PEG-PLA compared with PLA, PLGA and tissue culture polystyrene and led to a 2-fold increase in alkaline phosphatase activity and mineralization.
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PMID:Poly(D,L-lactic acid)-poly(ethylene glycol)-monomethyl ether diblock copolymers control adhesion and osteoblastic differentiation of marrow stromal cells. 1262 56

The purpose of this study was to achieve spinal fusion in the absence of bone graft material using a new, injectable, and semi-liquid synthetic polymer (polylactic acid polyethylene glycol [PLA-PEG] block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). Twenty-seven skeletally mature beagles underwent anterior thoracic spinal fusion at T9-T10. Group I (n = 9) was injected with 1 mL of PLA-PEG block copolymer carrier alone into space under the vertebral pleura and the anterior longitudinal ligament. Group II (n = 9) was injected with 1 mL of PLA-PEG carrier containing 500 microgram of rhBMP-2. Group III (n = 9) was injected with 1 mL of PLA-PEG carrier containing 1000 microgram of rhBMP-2. In the Group I animals, no evidence of new bone formation was noted at the implanted sites both radiographically and histologically. In contrast, all of the nine animals in Group III showed new bone formation in 12 weeks, and four of the nine animals in Group II showed bony mass at the injected sites. However, vertebral bony fusion was incomplete despite the significant amount of new bone formation in both groups that showed new bone formation. In addition to resulting in improvements in the surgical procedure, injection of rhBMP-2 and a synthetic polymer is useful for bone formation for spinal fusion.
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PMID:Anterior thoracic spinal fusion in dogs by injection of recombinant human bone morphogenetic protein-2 and a synthetic polymer. 1267 67


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