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

The objective of this paper is to study the effects of poly(ethylene glycol)-block-polylactide (PLA-PEG) nanoparticles on hepatic cells of mouse. Blank PLA-PEG nanoparticles have been successfully prepared and MTT assay suggested that the nanoparticles with HepG2 cell co-culture model did not cause significant changes in membrane integrity in controlled concentration range (0.001-0.1 mg/ml). Immunohistochemical analysis demonstrated that large dose of PLA-PEG nanoparticles injection (42.04 mg/kg, i.v.) did not induce hepatic cell apoptosis. From biochemical assay experiments, although the levels of SOD decreased and those of MDA, NOS increased after treatment with large dose of PLA-PEG nanoparticles injection (42.04 mg/kg, i.v.), they were all not significant (p>0.05). Then Kunming mice were treated with large dose of PLA-PEG nanoparticles (42.04 mg/kg, i.v.) and after 4 days total RNA was isolated to elucidate patterns of gene expression using a mouse cDNA-microarray (SuperArray). Treatment with nanoparticles resulted in over-expression of a lot of ATP-binding cassette (ABC) transporters, especially two ABC transporters (ABCA8 and ABCC5/MRP5), and down-regulation of GSTP1, in comparison with the control. ABCA8 could extrude low molecular weight polymers after PLA-PEG nanoparticles hydrolysis outside the cells. We also discovered that ABCC5 expressed multidrug resistance protein 5 (MRP5) to pump out conjugate (GS-X) of PLA-PEG nanoparticles with GSH. The results were confirmed by RT-PCR. Results of in vitro accumulation and efflux experiments indicated that about 51-52% (51.5% and 52.0%) intracellular PLA-PEG nanoparticles was expulsed after mouse primary hepatocytes reached a saturation uptake of nanoparticles during the concentration range of 750-1000 microg/ml. The results suggested that ABC transporters (especially ABCA8) pump out the polymers after hydrolysis from mouse hepatic cells and large dose of PLA-PEG nanoparticles make mouse hepatic cells gain drug resistance to PLA-PEG nanoparticles.
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PMID:Effect of poly(ethylene glycol)-block-polylactide nanoparticles on hepatic cells of mouse: low cytotoxicity, but efflux of the nanoparticles by ATP-binding cassette transporters. 1718 34

Phospholipase A2 (PLA(2)) has been implicated in neurodevelopmental processes and in the early development of the nervous system. We investigated the effects of the inhibition of calcium-dependent and calcium-independent subtypes of cytosolic PLA2 (cPLA2 and iPLA2) on the development and viability of primary cultures of cortical and hippocampal neurons. PLA2 in these cultures was continuously inhibited with methylarachidonyl-fluorophosphonate (MAFP), an irreversible inhibitor of cPLA2 and iPLA2, or with bromoenol lactone (BEL), an irreversible selective iPLA2 inhibitor. The effect of PLA2 inhibitors on the development of neuronal cultures was ascertained by total cell count and morphological characterisation. Neuronal viability was quantified with MTT assays. Inhibition of PLA2 resulted in reduction of neuritogenesis and neuronal viability, disrupting neuronal homeostasis and leading to neuronal death. We conclude that the functional integrity of both calcium-dependent and calcium-independent cytosolic PLA2 is necessary for the in vitro development of cortical and hippocampal neurons.
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PMID:Inhibition of phospholipase A2 reduces neurite outgrowth and neuronal viability. 1718 73

The objective of this study was to investigate the effect of formulation parameters (i.e. polymer molecular weight and homogenization speed) on various physicochemical and biological properties of cationic nanoparticles. Cationic nanoparticles were prepared using different molecular weights of poly(DL-lactide-co-glycolide) (PLGA) and poly(DL-lactic acid) (PLA) by double emulsion solvent evaporation at two different homogenization speeds, and were characterized in terms of size, surface charge, morphology, loading efficiency, plasmid release, plasmid integrity, cytotoxicity, and transfection efficiency. Cationic surfactant, cetyltrimethylammonium bromide (CTAB), was used to provide positive charge on the surface of nanoparticles. Reporter plasmid gWIZ Beta-gal was loaded on the surface of nanoparticles by incubation. Use of higher homogenization speed and lower molecular weight polymer led to a decrease in mean particle size, increase in zeta potential, increase in plasmid loading efficiency, and a decrease in burst release. The nanoparticles displayed good morphology as evident from scanning electron micrographs. In vitro cytotoxicity study by MTT assay showed a low toxicity. Structural integrity of the pDNA released from nanoparticles was maintained. Transfecting human embryonic kidney (HEK293) cells with nanoparticles prepared from low molecular weight PLGA and PLA resulted in an increased expression of beta-galactosidase as compared to those prepared from high molecular weight polymer. Our results demonstrate that the PLGA and PLA cationic nanoparticles can be used to achieve prolonged release of pDNA, and the plasmid release rate and transfection efficiency are dependent on the formulation variables.
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PMID:Preparation, characterization, cytotoxicity and transfection efficiency of poly(DL-lactide-co-glycolide) and poly(DL-lactic acid) cationic nanoparticles for controlled delivery of plasmid DNA. 1761 Oct 54

The duration of cisplatin release from most of the drug delivery devices seemed to be shorter than 14 days except large microparticles. The objective of this study was to fabricate and characterize cisplatin-loaded PLA microparticles, PLA/PLGA (30/70) composite microparticles, and fibers as formulations for long-term sustained delivery of cisplatin to treat C6 glioma in vitro by electrospray and electrospinning techniques. Cisplatin-loaded biodegradable microparticles with particle size of around 5 microm and fiber fabrics with diameter of 0.5-1.7 microm were obtained using electrospray and electrospinning techniques. Encapsulation efficiency and in vitro release of formulations were measured by ICP-OES. The encapsulation efficiency for different samples of microparticles was approximately from 33% to 72% and the fiber fabrics had encapsulation efficiency greater than 90%. Cisplatin-loaded microparticles showed typical characteristics of cisplatin release profile: a large initial burst followed by a sustained slow release of 35 days. The composite PLA/PLGA (30/70) microparticles could reduce the initial burst release of cisplatin because of their core-shell structures. In contrast, more than 75 days sustained release could be achieved by fiber fabric formulations without large initial burst. MTT assay was used to quantify the cytotoxicity of different formulations against C6 glioma cells. Microparticle formulations had slightly higher cytotoxicity than free drug. In contrast, the cytotoxicity of fiber fabrics formulation was around 4 times higher than of the free drug based on the actual amount of drug released. The microparticle and fiber fabric formulations presented may be promising for the sustained delivery of cisplatin to eliminate the undesired side effects caused by direct injection of cisplatin solution in systemic administration.
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PMID:Biodegradable microparticles and fiber fabrics for sustained delivery of cisplatin to treat C6 glioma in vitro. 1789 69

The growth of human primary keratinocytes and fibroblasts on PLA-PEO-PLA copolymer films was investigated as an intermediate stage of a strategy aimed at making implantable dermo-epidermal substitutes. Four PLA-PEO-PLA triblock copolymers with the same PEO block and different DL-lactic acid/ethylene oxide molar ratios (LA/EO) (0.8, 1.4, 1.8 and 2), were synthesized and characterized by 1H-nuclear magnetic resonance and infrared spectroscopy. The films made of these copolymers were more hydrophilic than PLA50 and than tissue culture polystyrene controls according to contact angles with water. Proliferation and adhesion of human skin cells were evaluated by MTT assay and by scanning electron microscopy. The presence of PEO in the triblock copolymers influenced cell adhesion and proliferation of fibroblasts, whereas keratinocyte adhesion and proliferation were not affected. These features emphasize the interest of PLA-PEO-PLA triblock copolymers to serve as better compounds than the racemic PLA previously investigated to make supports for human skin primary cells and scaffolds for skin engineering.
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PMID:Behaviors of keratinocytes and fibroblasts on films of PLA50-PEO-PLA50 triblock copolymers with various PLA segment lengths. 1791 33

A new poly(ethylene glycol) (PEG)-modified poly(D,L-lactic acid) (PLA) was synthesized by grafting maleic anhydride onto PLA and subsequently amidating with O,O'-bis-(2-aminopropyl) polypropylene glycol-block-polyethylene oxide-block-polypropylene glycol (H2N-PEG-NH2, Mw: 600). Its structure was confirmed by FTIR, DSC, 1H NMR, GPC, and ninhydrin test. The polymer is more hydrophilic compared with PLA according to contact angle tests, and is degradable as determined from its pH and mass changes during degradation. The polymer shows a 62.7% decrease in BSA absorption compared with PLA when dried in air, and a 82.76% decrease when dried under 65% humidity, as measured by fluorospectrophotometry. The polymer promotes adhesion and proliferation of osteoblasts, determined by MTT assay. With this new polymer, spherical nanoscale aggregates encapsulated with or without hydrophilic dye are formed spontaneously in water, visualized by inverted microscope and AFM. The particle size is concentration dependent as confirmed by dynamic light scattering, and its critical micelle concentration was 1.124 microg/mL as determined by a fluorescence method. The good hydrophilicity, degradability, cellular compatibility, protein-resistance, self-aggregation, and reactivity of the polymer may lead to its potential applications in drug delivery.
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PMID:Development of a new poly(ethylene glycol)-graft-poly(D,L-lactic acid) as potential drug carriers. 1843 84

Poly(lactic acid) (PLA) was modified by maleic anhydride (MAH), then the resultant MAH modified PLA (MPLA) was acylated with ethylenediamine (EDA), so EDA-MAH modified PLA (EMPLA) was prepared. The results of DSC, FT-IR and NMR testified that MAH and EAD were successfully introduced into the original polymer. The hydrophilicity of EMPLA was considerably increased compared with that of PLA. The degradation experiment showed that the introduction of EDA into the original polymer could neutralize the carboxyl end groups of the degradation products. The results of SEM and MTT of rat osteoblasts cultured in vitro showed that the cytocompatibility and cell adhesion of the modified materials were significantly increased compared with the original polymer, especially EMPLA; the number of cells were obviously increased and cells attached firmly to the material; these were ascribed to the EDA neutralizing the carboxyl end groups of the degradation products.
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PMID:Two-step modification of poly(D, L-lactic acid) by ethylenediamine-maleic anhydride. 1845 89

A terpolyester consisting of 3-hydroxybutyrate (3HB), 4-hydroxybutyrate (4HB) and 3-hydroxyhexanoate (3HHx), abbreviated as P(3HB-co-4HB-co-3HHx), was studied for possible application as an implant biomaterial. L929 mouse fibroblasts, MC3T3-E1 murine osteoblasts and a human cell line of immortalized human keratinocyte (HaCat cells) were used to study the biocompatibility of P(3HB-co-4HB-co-3HHx). Cell morphology and cell activity were studied using scanning electron microscopy (SEM) and the MTT assay, respectively. All three cell types showed higher activities when grown on films of P(3HB-co-4HB-co-3HHx) compared with their growth on poly(lactic acid) (PLA), co-polyester PHBHHx films and on polylysine-coated plates (blank), respectively. The three cell types grown on the terpolyester also demonstrated a well-spread cell shape and large number of pseudopods due to strong cell-cell and cell-material interactions. It was clearly observed that P(3HB-co-4HB-co-3HHx) had a much faster degradation rate than PHBHHx after 15 weeks of incubation in phosphate-buffered saline under dynamic conditions. The results proved that the terpolyester had favorable biocompatibility and biodegradability compared with the well-studied polyesters PLA and PHBHHx.
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PMID:In vitro biocompatibility and degradation of terpolyester 3HB-co-4HB-co-3HHx, consisting of 3-hydroxybutyrate, 4-hydroxybutyrate and 3-hydroxyhexanoate. 1897 27

A novel type of biodegradable/biocompatible amphiphilic hyperbranched copolymer (H40-PLA-b-MPEG) was synthesized. Its micellar properties were studied by DLS, fluorescence spectroscopy and TEM. The drug release profile showed that the H40-PLA-b-MPEG micelles provide an initial burst release, followed by a sustained release of the entrapped hydrophobic model drug over a period of 4 to 58 h. The copolymer degraded hydrolytically within 6 weeks under physiological conditions. The MTT assay showed no obvious cytotoxicity against a human endothelial cell line at a concentration range of 0-400 microg x mL(-1). These results indicate that the H40-PLA-b-MPEG micelles have great potential as hydrophobic drug delivery carriers.
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PMID:Amphiphilic multi-arm block copolymer based on hyperbranched polyester, poly(L-lactide) and poly(ethylene glycol) as a drug delivery carrier. 1908 67

The aim of this study was to investigate the effects of the surface charges on the in vitro macrophage cellular uptake and in vivo blood clearance and biodistribution of the hemoglobin-loaded polymeric nanoparticles (HbPNPs). The surface charges of the HbPNPs fabricated from mPEG-PLA-mPEG were modulated with cationized cetyltrimethylammonium bromide (CTAB) and anionized sodium dodecyl sulphate (SDS), respectively. In vitro macrophage cellular uptake and in vivo biodistribution of the coumarin 6-labeled HbPNPs with different electric charges were investigated, and the half-lives in the circulation were pharmacokinetically analyzed. The particle sizes of the HbPNPs were all below 200 nm with a narrow size distribution and high encapsulation efficiency (>84%). And the zeta-potentials of the untreated, cationized and anionized HbPNPs in phosphate buffered sodium chloride solution (PBS) were -12.3, +3.28 and -25.4 mV, respectively. The HbPNPs did not occur significant aggregation or sedimentation, even after 5 days. Compared with the untreated HbPNPs, 1-fold decrease/increase of the uptake percentage associated with the cationized/anionized HbPNPs was observed. In vivo experiment demonstrated that the calculated half-life of the cationized HbPNPs was 10.991 h, 8-fold longer than that of the untreated HbPNPs (1.198 h). But the anionized HbPNPs displayed opposite effect. Furthermore, the cationized HbPNPs mainly accumulated in the liver, lung and spleen after 48 h injection. MTT results showed that the HbPNPs with different surface charges all exhibited slight toxicity. These results demonstrated that the CTAB-modulated HbPNPs with low positive charge and suitable size have a promising potential as a long-circulating oxygen carrier system with desirable biocompatibility and biofunctionality.
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PMID:Long-circulation of hemoglobin-loaded polymeric nanoparticles as oxygen carriers with modulated surface charges. 1945 5


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