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

In-stent restenosis is a process that occurs in 10-50% of cases currently treated with stent and it is caused by an abnormal smooth muscle cell (SMC) proliferation and migration in the vascular lumen. One of the most promising strategy to reduce restenosis is stent coating with biodegradable polymers to deliver in situ anti-proliferative drugs. Poly(D,L)lactic acid (P(D,L)LA), one of the most interesting candidate for stent coating, has been observed to induce inflammation and neointimal proliferation. In our laboratory, we developed P(D,L)LA enriched with Vitamin E (Vit.E), an anti-oxidative and anti-inflammatory agent that reduces also SMC proliferation. In order to evaluate the in vitro cellular behaviour of neointima cells onto Vitamin E-enriched P(D,L)LA, cell adhesion and proliferation along with the expression of two SMC migration markers (MMP-9 and hyaluronic acid receptor CD44) were measured in rat vascular SMC A10 cells seeded onto control P(D,L)LA (PLA) and P(D,L)LA films containing 10-30% (w/w) Vit.E (PLA10-30). Cell adhesion, proliferation and MMP-9 production were unaffected by the Vit.E presence in the PLA films after 24 h, while proliferation was slowed or blocked after 48 and 72 h onto PLA10, 20 and 30. MMP-9 production was almost blocked and CD44 density decreased significantly after 72 h for cells grew onto PLA30 compare to cells seeded onto PLA. These data indicate that Vit.E-enriched P(D,L)LA could be an interesting polymer for stent coating.
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PMID:Cellular behavior of neointima-like cells onto vitamin E-enriched poly(D,L)lactic acid. 1753 64

The aim of this study was to define the parameters determining an optimized yield of monodisperse, nanosized particles after nanoprecipitation of a biodegradable polymer, with a view to industrial scale-up the process. Poly(d,l)-lactides (PLAs) from a homologous series of different molar masses were nanoprecipitated at different initial polymer concentrations from two organic solvents, acetone and tetrahydrofuran (THF), into water without surfactant according to a standardized procedure. Quasi-elastic light scattering and gel permeation chromatography with universal detection were used respectively to size the particles and to determine the molar mass distribution of the polymeric chains forming both nanoparticles and bulk aggregates. The intrinsic viscosity of the polymers as a function of molar mass and solvent were determined by kinematic viscosity measurements in organic solutions. High yields of small nanoparticles were obtained with polymers of lower molar mass (22600 and 32100 g/mol). For a given polymer concentration in organic solution, the particle diameter was always lower from acetone than from THF. For initial molar masses higher than 32100 g/mol, only dilute organic solutions gave significant yields of nanoparticles. Furthermore, polymer mass fractionation occurred with increasing initial molar mass and/or concentration: the nanoparticles were formed by polymeric chains of molar masses significantly lower than the average initial one. In general, nanoparticle production was satisfactory when the initial organic solution of polymer was in the dilute rather than the semi-dilute regime. Moreover, acetone, which acted as a theta solvent for PLA, always led to smaller particles and better yields than THF.
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PMID:Influence of polymer behaviour in organic solution on the production of polylactide nanoparticles by nanoprecipitation. 1761 82

Camptothecin (CPT) is an alkaloid that displays considerable antitumour activity, but clinical use has been limited by its poor water solubility and the instability of the lactone moiety (active form) in physiological media. We have therefore formulated the drug into nanocarrier systems in an attempt to improve its therapeutic properties. This study evaluates the effect of intraperitoneally administered stealth and non-stealth nanocapsules containing CPT on lung metastatic spread in mice inoculated with B16-F10 melanoma cells, and on the cytotoxic activity against B16-F10 melanoma cells in-vitro. Poly (D,L-lactide) PLA (non-stealth) and methoxy polyethylene glycol-(D,L-lactide) (PLA-PEG) (stealth) nanocapsules (49 and 66.6 kDa) were prepared by interfacial deposition of preformed polymer. CPT, as free drug or as drug-loaded nanocapsules, was administrated at a dose of 0.5 mg kg(-1) at 3-day intervals for 17 days. Free drug and CPT-loaded nanocapsules reduced the number of metastatic nodules by 45.09-91.76% (P < 0.05 vs positive control). However, only CPT-loaded PLA-PEG 49 kD nanocapsules significantly decreased the number of lung metastases when compared with free drug (P < 0.05). The administration of CPT-loaded nanocapsules and free drug did not result in neutropenia at the administered dose. The improved effectiveness of pegylated nanocapsules was attributed to protection of the drug by nanoencapsulation and to reduced uptake of particles by macrophages located in the lymph nodes. This assumption was supported by the in-vitro study, in which both PLA and 49 kDa PLA-PEG nanocapsules containing CPT were more cytotoxic than the free drug against B16-F10 melanoma cells.
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PMID:Stealth and non-stealth nanocapsules containing camptothecin: in-vitro and in-vivo activity on B16-F10 melanoma. 1791 Aug 10

The objective of this study was to develop novel absorbable films suitable for use as a tissue-engineering scaffold for keratinocytes as a therapy for replacement of damaged skin. Poly(4-hydroxybutyrate) (P(4HB)) and poly (3-hydroxybutyrate) (P(3HB)) were blended with small amounts of the polysaccharides hyaluronic acid (HA), chitosan (CH), pectin and alginic acid, and were solution cast to produce porous films. The resulting composites had favorable mechanical properties, and these films were compared with two commercially available implantable films made of poly(L-lactide-co-D,L-lactide) (PLA copolymer) and HA benzyl ester. Tensile testing demonstrated that a high level of flexibility of P(4HB) was retained in the P(4HB)-polysaccharide composite films, whereas the P(3HB) film and its polysaccharide composites were stiffer and more brittle. The proliferation kinetics of adherent HaCaT keratinocytes on the films was examined in vitro. The porous surface of the P(4HB) and P(3HB) films blended with HA or CH promoted the growth of keratinocytes significantly. The order of maximum cell numbers on these films was P(4HB)/HA > P(4HB)/CH > P(3HB)/HA > P(3HB)/CH > P(3HB)/pectin > P(3HB)/alginic acid. Scanning electron microscopy and confocal laser scanning microscopy revealed differences in cell growth. Cells formed clusters on P(3HB) and its composites, while the cells grew as a confluent layer on P(4HB) and its composites. HaCaT cells formed large numbers of filaments only on P(4HB) films, indicating the excellent biocompatibility of this material. For the nonporous PHB films, the proliferation rate of cells was found to increase with decreasing hydrophobicity in the order: P(4HB) > P(3HB)/P(4HB) blend > P(3HB).
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PMID:Growth of keratinocytes on porous films of poly(3-hydroxybutyrate) and poly(4-hydroxybutyrate) blended with hyaluronic acid and chitosan. 1793 18

Poly(DL-lactic acid) (PLA)/poly(ethylene glycol)-block-poly (propylene glycol)-block-poly(ethylene glycol) copolymer (PEG-PPG-PEG) nanoparticles loaded with camptothecin (CPT), called CPT-NP, were prepared and examined for particle size change and drug release in phosphate-buffered saline, pH 7.4, (PBS), and drug biodistribution profiles in mice bearing sarcoma 180 solid tumor. CPT-NP kept an almost constant mean size and exhibited an initial rapid release of approximately 20%, following by very slow release. As compared with CPT solution, CPT-NP showed higher tissue accumulation and better tumor localization, which were considered essentially associated with the better efficacy of CPT-NP reported in the previous study.
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PMID:Particle characteristics and biodistribution of camptothecin-loaded PLA/(PEG-PPG-PEG) nanoparticles. 1819 17

The present study was conducted to investigate the use of hydrodynamic flow focusing for the generation of biodegradable polymer microspheres encapsulating the anticancer drug camptothecin. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactide) (PLA) were used as the matrix materials. Camptothecin was dissolved in the disperse phase and microspheres with a mean size between 2 and 3 microm generated using hydrodynamic flow focusing. When up to 1 wt.% of the drug was added to PLA, the drug encapsulation efficiency was 64%. For PLGA, the drug encapsulation efficiency was between 39 and 46%. Drug release from PLA particles was rapid and complete within 6 h, while drug release from PLGA particles showed no burst effect and followed a first order release profile. The encapsulated camptothecin stayed in its active lactone form, as shown by HPLC, and was able to exert cell toxic effects as shown by a cell viability assay. Hydrodynamic flow focusing is a promising tool for the preparation of drug-releasing biodegradable microspheres typically made by solvent evaporation and/or solvent extraction, as indicated by the successful encapsulation of the anticancer drug camptothecin.
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PMID:Use of hydrodynamic flow focusing for the generation of biodegradable camptothecin-loaded polymer microspheres. 1831 91

Concerns over disease transmission, high costs and limited supply have led to interest in synthetic grafts in the field of impaction bone grafting (IBG). Poly(DL-lactic acid) (PLA) grafts are attractive alternatives due to their biocompatibility, established safety and versatile manufacturing process. This study examined the potential of PLA scaffolds augmented with human bone marrow stromal cells (HBMSCs) in IBG. In vitro and in vivo studies were performed on impacted morsellised PLA seeded with HBMSC and compared to PLA alone. In vitro samples were incubated under osteogenic conditions and in vivo samples were implanted subcutaneously into severely compromised immunodeficient mice, for 4 weeks. Biochemical, histological, mechanical and 3D micro-computed tomography analyses were performed. HBMSC viability, biochemical activity and histological evidence of osteogenic cellular differentiation, post-impaction were observed in vitro and in vivo in PLA/HBMSC samples compared to impacted PLA alone. In vitro PLA/HBMSC samples demonstrated evidence of mechanical enhancement over PLA alone. In vivo studies showed a significant increase in new bone and blood vessel formation in the PLA/HBMSC constructs compared to PLA alone. With alternatives to allograft being sought, these studies have demonstrated PLA/HBMSC living composites, to be a potential prospect as a biological bone graft extender for future use in the field of IBG.
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PMID:The application of human bone marrow stromal cells and poly(dl-lactic acid) as a biological bone graft extender in impaction bone grafting. 1845 20

Poly(lactide)-block-poly(ethylene oxide)-block-poly(lactide) (PLA-PEO-PLA) triblock copolymers are known to form physical hydrogels in water as a result of the polymer's amphiphilicity. Their mechanical properties, biocompatibility, and biodegradability have made them attractive for use as soft tissue scaffolds. However, the network junction points are not covalently cross-linked, and in a highly aqueous environment these hydrogels adsorb more water, transform from gel to sol, and lose the designed mechanical properties. In this article, a hydrogel was formed by the use of a novel two-step approach. In the first step, the end-functionalized PLA-PEO-PLA triblock was self-assembled into a physical hydrogel through hydrophobic micelle network junctions, and in the second step, this self-assembled physical network structure was locked into place by photo-cross-linking the terminal acrylate groups. In contrast with physical hydrogels, the photo-cross-linked gels remained intact in phosphate-buffered solution at body temperature. The swelling, degradation, and mechanical properties were characterized, and they demonstrated an extended degradation time (approximately 65 days), an exponential decrease in modulus with degradation time, and a tunable shear modulus (1.6-133 kPa). We also discuss the various constitutive relationships (Hookean, neo-Hookean, and Mooney-Rivlin) that can be used to describe the stress-strain behavior of these hydrogels. The chosen model and assumptions used for data fitting influenced the obtained modulus values by as much as a factor of 3.5, which demonstrates the importance of clearly stating one's data fitting parameters so that accurate comparisons can be made within the literature.
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PMID:Photo-cross-linked PLA-PEO-PLA hydrogels from self-assembled physical networks: mechanical properties and influence of assumed constitutive relationships. 1881 40

We developed a new strategy to prepare folate-decorated nanoparticles of biodegradable polymers for Quantum dots (QDs) formulation for targeted and sustained imaging for cancer diagnosis at its early stage. Poly(lactide)-vitamin E TPGS (PLA-TPGS) copolymer and vitamin E TPGS-carboxyl (TPGS-COOH) copolymer were synthesized. Their blend at various weight ratio was used to prepare folate-decorated nanoparticles (NPs) for QDs formulation to improve their imaging effects and reduce their side effects. The TPGS-COOH on the NP surface was designed to conjugate folate-NH(2) with advantage to make the targeting effect adjustable. The size of such NPs was found in the range of 280-300nm. In vitro cellular uptakes of such NPs were investigated with confocal laser scanning microscopy (CLSM), which demonstrated much higher internalization of the folate-decorated QDs-loaded PLA-TPGS/TPGS-COOH NPs by MCF-7 breast cancer cells which are of over-expression of folate receptors than the cellular uptake by NIH 3T3 fibroblast cells which are of low expression of folate receptors. Compared with the free QDs, the QDs formulated in the PLA-TPGS/TPGS-COOH NPs showed lower in vitro cytotoxicity for both of MCF-7 cells and NIH 3T3 cells. Additionally, our findings indicated that under same conditions, cytotoxicity of QDs formulated in the PLA-TPGS/TPGS-COOH NPs is lower for normal cells such as NIH 3T3 cells than that for breast cancer such as MCF-7 breast cancer cells due to folate targeting effect. Targeted imaging by QDs formulated in folate-decorated PLA-TPGS/TPGS-COOH nanoparticles with better effects and less side effects is feasible.
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PMID:Targeting and imaging cancer cells by folate-decorated, quantum dots (QDs)- loaded nanoparticles of biodegradable polymers. 1906 89

Poly(epsilon-caprolactone)/polylactide blend (PCL/PLA) is an interesting biomaterial because PCL and PLA present good complementarity in their physical properties and biodegradability. However, the thermodynamic incompatibility between two component polymers restricts further applications of their blend. In this work, we used functionalized multiwalled carbon nanotube (MWCNT) to control the morphology of immiscible PCL/PLA blend. The ternary PCL/PLA/MWCNTs composites were hence prepared by melt mixing for the morphology and the properties investigation. It is interesting to find that the functionalized MWCNTs are selectively dispersed in the matrix PCL phase and on the interface between two polymer phases, leading to simultaneous occurrence of thermodynamically and kinetically driven compatibility. Those interface-localized MWCNTs prevent coalescence of the discrete domains and enhance the phase interfacial adhesion as well. As a result, the phase morphology of the ternary composites is improved remarkably in contrast to that of the blank PCL/PLA blend. Owing to that unique selective interface-localization and improved phase morphology, the ternary composites present far lower rheological and conductive percolation thresholds than those of the binary composites, and also present extraordinary mechanical properties even at very low loading levels of the MWCNTs. Therefore, the amphiphilic MWCNTs are believed to act as the reinforcements as well as the compatibilizer in the immiscible PCL/PLA blend.
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PMID:Selective localization of multiwalled carbon nanotubes in poly(epsilon-caprolactone)/polylactide blend. 1914 Jul 30


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