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

An approach is proposed using Vibrio cholerae (VC)-loaded microparticles as oral vaccine delivery systems for improved vaccine bioavailability and increased therapeutic efficacy. The VC-loaded microparticles were prepared with 50:50 poly(DL-lactide-co-glycolide) (PLG), 75:25 poly(DL-lactide-co-glycolide) and poly(lactide acid) (PLA)/PEG blend copolymers by the solvent evaporation method. VC was successfully entrapped in three types of microparticles with loading efficiencies and loading levels as follows: 50:50 PLG systems: 97.8% and 55.4 +/- 6.9 micro g/mg; 75:25 PLG systems: 89.2% and 46.5 +/- 4.4 micro g/mg; PLA/PEG-blended systems: 82.6% and 53.7 +/- 5.8 micro g/mg. The different distributions of VC in the core region and on the surface were as follows: 50:50 PLG systems 25.7 +/- 1.9 and 6.2 +/- 0.9 micro g/mg; 75:25 PLG systems: 25.8 +/- 2.2 and 3.6 +/- 0.4 micro g/mg; PLA/PEG-blended systems: 32.4 +/- 2.1 and 5.2 +/- 1.0 micro g/mg, respectively. In vitro active release of VC was affected mainly by matrix type and VC-loaded location in microparticles. The therapeutic immunogenic potential of VC loaded with 50:50 PLG, 75:25 PLG and PLA/PEG-blended microparticles was evaluated in adult mice by oral immunization. Significantly higher antibody responses and serum immunoglobin Ig G, IgA and IgM responses were obtained when sera from both VC-loaded 75:25 PLG and PLA/PEG-blended microparticles immunized mice were titrated against VC. The most immunogenicity in evoking serum IgG, IgA and IgM responses was immunized by VC-loaded PLA/PEG-blended microparticles, and with VC challenge in mice, the survival rate (91.7%).
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PMID:Inactive Vibrio cholerae whole-cell vaccine-loaded biodegradable microparticles: in vitro release and oral vaccination. 1471 89

Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zeta-potential analyzer and X-ray photoelectron spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography. The effects of various formulation parameters were evaluated. The prepared nanoparticles were found of spherical shape with size less than 100 nm. Zeta potential measurement and XPS analysis demonstrated the presence of PEG layer on the particle surface. Viscosity of the organic phase was found to be one of the main process factors for the size determination. The EE was found to be greatly influenced by the drug loading. The drug release pattern was biphasic with a fast release rate followed by a slow one. The particle suspension exhibited good steric stability in vitro. Such a nanoparticle formulation of paclitaxel can be expected to have long-circulating effects in circulation.
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PMID:Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. 1496 62

In this work, the producing of a biodegradable poly(l-lactide) (PLA)/poly(ethylene glycol) (PEG) microcapsule by emulsion solvent evaporation method was investigated. The effect of PEG segments added to the PLA microcapsules on the degradation, size distribution, and release behavior was studied. According to the results, PLA/PEG copolymer was more hydrophilic than PLA homopolymer, and with lower glass transition temperature. The surface of PLA/PEG microcapsules was not as smooth as that of PLA microcapsules, the mean diameters of prepared PLA and PLA/PEG microcapsules were 40 and 57 microm, respectively. And spherical forms were observed by the image analyzer and the scanning electron microscope (SEM). Drug release from microcapsules was affected by the properties of PLA/PEG copolymers determined by UV-vis spectra. It was found that the drug release rates of the microcapsules were significantly increased with adding of PEG, which explained by increasing hydrophilic groups.
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PMID:Preparation and characterization of biodegradable poly(l-lactide)/poly(ethylene glycol) microcapsules containing erythromycin by emulsion solvent evaporation technique. 1497 10

Controlled release polymer vesicles are prepared using hydrolysable diblock copolymers of polyethyleneglycol-poly-l-lactic acid (PEG-PLA) or polyethyleneglycol-polycaprolactone (PEG-PCL). Encapsulation studies with a common anti-cancer agent, doxorubicin, show loading comparable to liposomes. Rates of encapsulant release from the hydrolysable vesicles are accelerated with an increased proportion of PEG but are delayed with a more hydrophobic chain chemistry (i.e. PCL). Rates of release also rise linearly with the molar ratio of degradable copolymer blended into membranes of a non-degradable, PEG-based block copolymer (PEG-polybutadiene (PBD)). With all compositions, in both 100 nm and giant vesicles, the average release time (from hours to days) reflects a highly quantized process in which any given vesicle is either intact and retains its encapsulant, or is porated and slowly disintegrates. Poration occurs as the hydrophobic PLA or PCL block is hydrolytically scissioned, progressively generating an increasing number of pore-preferring copolymers in the membrane. Kinetics of this evolving detergent mechanism overlay the phase behavior of amphiphiles with transitions from membranes to micelles allowing controlled release.
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PMID:Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis-triggered controlled release vesicles. 1506 28

Bone morphogenetic proteins (BMPs) are biologically active molecules capable of inducing new bone formation, and show potential for clinical use in bone defect repair. However, an ideal system for delivering BMPs that can potentiate their bone-inducing ability and provide initial mechanical strength and scaffold for bone ingrowth has not yet been developed. In this study, to construct a carrier/scaffold system for BMPs, we combined two biomaterials: interconnected-porous calcium hydroxyapatite ceramics (IP-CHA), and the synthetic biodegradable polymer poly D,L,-lactic acid-polyethyleneglycol block co-polymer (PLA-PEG). We used a rabbit radii model to evaluate the bone-regenerating efficacy of rhBMP-2/PLA-PEG/IP-CHA composite. At 8 weeks after implantation, all bone defects in groups treated with 5 or 20 microg of BMP were completely repaired with sufficient strength. Furthermore, using this carrier scaffold system, we reduced the amount of BMP necessary for such results to about a tenth of the amount needed in previous studies, probably due to the superior osteoconduction ability of IP-CHA and the optimal drug delivery system provided by PLA-PEG, inducing new bone formation in the interconnected pores. The present findings indicate that the synthetic biodegradable polymer/IP-CHA composite is an excellent combination carrier/scaffold delivery system for rhBMP-2, and that it strongly promotes the clinical effects of rhBMP-2 in bone tissue regeneration.
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PMID:Potentiation of the activity of bone morphogenetic protein-2 in bone regeneration by a PLA-PEG/hydroxyapatite composite. 1519 82

The purpose of this study was to prepare poly(ethylene glycol) (PEG)ylated octreotide and investigate the stability against acylation by polyester polymers such as poly(lactic acid) and poly(lactic-co-glycolic acid). Octreotide was modified by reaction with monomethoxy PEG-propionaldehyde (molecular weight 5,000) in the presence of sodium cyanoborohydride. The mono-PEGylated fraction was isolated by reversed-phase high-performance liquid chromatography (HPLC) and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Circular dichroism demonstrated no significant secondary structural differences between mono-PEGylated octreotide (mono-PEG-octreotide) and intact octreotide. As a test system for the stability study against acylation reaction, lactic acid (LA) solutions with various concentrations and pH values were prepared with water dilution and subsequent accelerated equilibration at 90 degrees C for 24 hours. Native octreotide was found to be acylated in all the diluted LA solutions with different concentrations (42.5%, 21.3%, and 8.5%, wt/wt) and pH values (2.25, 1.47, and 1.85, respectively). The remaining amounts of intact octreotide continuously decreased to 50% through 30 days of incubation at 37 degrees C. MALDI-TOF MS identified the octreotide to be acylated by LA units. However, acylation reaction of mono-PEG-octreotide in LA solutions was negligible, and the remaining amounts of intact one through 30 days of incubation in LA solutions were also comparable to the initial concentration. These data suggest that mono-PEG-octreotide may prevent the acylation reaction in degrading PLA microspheres and possibly serve as a new source for somatostatin microsphere formulation.
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PMID:Preparation and stability of poly(ethylene glycol) (PEG)ylated octreotide for application to microsphere delivery. 1519 67

The successful incorporation and sustained release of a hydrophilic antibiotic drug (Mefoxin, cefoxitin sodium) from electrospun poly(lactide-co-glycolide) (PLGA)-based nanofibrous scaffolds without the loss of structure and bioactivity was demonstrated. The morphology and density of the electrospun scaffold was found to be dependent on the drug concentration, which could be attributed to the effect of ionic salt on the electrospinning process. The drug release behavior from the electrospun scaffolds and its antimicrobial effects on Staphylococcus aureus cultures were also investigated. In all tested scaffolds, the maximum dosage of drug was released after 1 h of incubation in water at 37 degrees C. The usage of the amphiphilic block copolymer (PEG-b-PLA) reduced the cumulative amount of the released drug at earlier time points and prolonged the drug release rate at longer times (up to a 1-week period). The antibiotic drug released from these electrospun scaffolds was effective in their ability to inhibit Staphylococcus aureus growth (>90%). The combination of mechanical barriers based on non-woven nanofibrous biodegradable scaffolds and their capability for local delivery of antibiotics increases their desired utility in biomedical applications, particularly in the prevention of post-surgical adhesions and infections.
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PMID:Incorporation and controlled release of a hydrophilic antibiotic using poly(lactide-co-glycolide)-based electrospun nanofibrous scaffolds. 1524 88

The aim of the study was to investigate the effect of the size and PEG coating density of Poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nano- and microparticles on their transport across the nasal mucosa. Particles were made of PLA-PEG copolymers of two different molecular weights (Mw: 37 and 28 kDa) and also PLA of Mw 28 kDa, and prepared using different techniques (simple emulsion (o/w), double emulsion (w/o/w), and nanoprecipitation techniques). The particles were characterized for their size, zeta potential, morphology [Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM)], and PEG coating efficiency. Additionally, the transport of rhodamine 6G-labelled PLA-PEG and PLA particles across the rat nasal mucosa was investigated by Confocal Laser Scanning Microscopy (CLSM). The results showed that the size of PLA-PEG nanoparticles varied between 150 and 300 nm and their zeta potential between -10 and -22 mV depending on both the polymer Mw and the preparation technique. Moreover, the PEG coating efficiency (amount of PEG on the surface with respect to the total amount of PEG in the particles) was high (between 75% and 92%) and affected by the PLA Mw and also by the particles preparation technique. The greatest PEG surface density was achieved for lowest Mw PLA-PEG, using the O/W emulsification technique. The CLSM images of nasal epithelia from rats showed the importance of the PEG coating density and the size on the transmucosal transport of the fluorescent nanoparticles. More specifically, PLA-PEG particles with a high PEG coating density and a small size were more significantly transported than noncoated PLA nanoparticles and also than PLA-PEG nanoparticles with a lower coating density. In conclusion, these results showed the important role that the PEG coating has on the efficacy of PLA-PEG nanoparticles as nasal drug carriers.
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PMID:Transport of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density. 1526 15

A new type of degradable biomaterial with bone-inducing capacity was made by combining porous beta-tricalcium phosphate (beta-TCP) with a delivery system for recombinant human bone morphogenetic protein-2 (rhBMP-2). The BMP delivery system consisted of a block copolymer composed of poly-D,L-lactic acid with random insertion of p-dioxanone and polyethylene glycol (PLA-DX-PEG), a known biocompatible and biodegradable material. The efficacy of this biomaterial in terms of its bone-inducing capacity was examined by ectopic bone formation in the dorsal muscles of the mouse. In the beta-TCP implants coated with the PLA-DX-PEG polymer containing more than 0.0025% (w/w) of rhBMP-2, new ectopic bone tissues with marrow were consistently found on the surface of implants. The radiographic density of beta-TCP was diminished in a time-dependent manner. On histological examination, numerous multinucleated osteoclasts with positive tartrate-resistant acid-phosphatase (TRAP) staining were noted on the surface of the beta-TCP. These experimental results indicate that beta-TCP implants coated with synthetic rhBMP-2 delivery system might provide effective artificial bone-graft substitutes with osteoinductive capacity and biodegradable properties. In addition, this type of biomaterial may require less rhBMP-2 to induce significant new bone mass.
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PMID:A new bone-inducing biodegradable porous beta-tricalcium phosphate. 1529 19

This report presents an overview of the potential of nanoparticles as nasal carriers for drug/vaccine administration. In addition, this report shows, for the first time, the efficacy of polylactic acid nanoparticles coated with a hydrophilic polyethyleneglycol coating (PEG-PLA nanoparticles) as carriers for the nasal transport of bioactive compounds. For this purpose, tetanus toxoid (TT), a high molecular weight protein (Mw 150,000 Da), was chosen as a model antigen and encapsulated in the PEG-PLA nano- and microparticles (200 nm and 1.5 microm respectively). These nanosystems were first characterized for their stability in the presence of lysozyme and also for their size, electrical charge, loading efficiency, in vitro release of antigenically active toxoid and afterwards, these formulations were administered intranasally to mice and the systemic and mucosal anti-tetanus responses were evaluated for up to 24 weeks. Additionally, PEG-PLA particles labeled with rhodamine 6G were administered intranasally to rats in order to visualize their interaction with the nasal mucosae by fluorescence microscopy. Their behavior was compared with that of the well known PLA nanoparticles (200 nm). The results showed that PLA nanoparticles suffered an immediate aggregation upon incubation with lysozyme, whereas the PEG-coated nanoparticles remained totally stable. The antibody levels elicited following i.n. administration of PEG-coated nanoparticles were significantly higher than those corresponding to PLA nanoparticles. Furthermore, PEG-PLA nanoparticles generated an increasing and a long lasting response. The qualitative fluorescence microscopy studies revealed that PEG-PLA particles are able to cross the rat nasal epithelium. These studies indicate that the PEG coating around the particles has a role in stabilizing PLA particles in mucosal fluids and that it facilitates the transport of the nanoencapsulated antigen, hence eliciting a high and long lasting immune response.
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PMID:PEG-PLA nanoparticles as carriers for nasal vaccine delivery. 1529 69


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