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

Bovine serum albumin (BSA)-loaded poly(lactide) (PLA) particles were prepared using an electrospraying technique, in which a sufficiently strong electric field was applied to overcome the surface tension of a droplet. A comprehensive investigation was conducted on the effects of independent variables organic/aqueous phase volume ratio and BSA/PLA weight ratio on the dependent variables viscosity, electrical conductivity, surface tension; the morphologies, sizes, and yields of particles; BSA encapsulation efficiency (EE); and in vitro release. An increase in the organic/aqueous phase ratio increased the viscosity and decreased the electrical conductivity of the emulsions, while the viscosity increased with BSA/PLA ratio. In general, spherical particles, with smooth surface and without visible pores, were observed. However, the spherical shape was lost as the organic/aqueous phase ratio decreased and the BSA/PLA ratio decreased. The particle sizes ranged from 0.84+/-0.18 to 3.95+/-0.51mum and the yield was in the range of 64.3+/-1.8 to 80.1+/-2.6%. EE of BSA was between 22.9 and 80.6%, and was increased with organic/aqueous phase ratio and decreased with increasing BSA/PLA ratio. In vitro release of BSA from the particles was reduced with increasing organic/aqueous phase ratio and was enhanced by the increase in the BSA/PLA ratio.
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PMID:Electrospray encapsulation of water-soluble protein with polylactide. Effects of formulations on morphology, encapsulation efficiency and release profile of particles. 1669 38

The aim of this work was to develop a novel strategy for the formulation of biodegradable PLA microspheres as delivery systems for proteins or peptides. The strategy is based on the exploitation of the gel-sol transition of the thermoreversible Pluronic F127 gel. The gel allows the formation of the particles without be co-entrapped in the matrix. The microspheres prepared using the novel technique (TG-Ms, or thermoreversible gel-method microspheres) were characterized in vitro (as concerns the size, the morphology, the protein encapsulation, the release and the protein distribution in the polymer matrix), in comparison with microspheres prepared using the classical double emulsion/solvent evaporation method (w/o/w-Ms). Two types of bovine serum albumin (BSA), with different water solubility, were used as model proteins. TG-Ms exhibited small size (7-50 m) and high protein content (8.6%, w/w) regardless of the BSA water solubility, in contrast with w/o/w-Ms, which revealed a size range of 100-130 microm and a protein content related to the BSA water solubility. TG-Ms, in spite of their smaller size respect of the w/o/w-Ms, displayed a reduced initial burst effect and a higher rate in the second release phase that resulted in a quasi-constant profile. The release behavior of the TG-Ms may be attributable to both the localization of the protein in the particle core, as shown by the confocal laser scanning microscopy analysis on labeled-BSA loaded microspheres, and the few pores in the matrix, as shown by the scanning electron microscopy. A working hypothesis about the mechanism of the particle formation was also discussed.
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PMID:PLA-microparticles formulated by means a thermoreversible gel able to modify protein encapsulation and release without being co-encapsulated. 1681 57

Bovine serum albumin (BSA) was encapsulated with poly (lactide) (PLA) using an electrospray technique in which a sufficiently strong electric field was applied to overcome the surface tension of a droplet and to produce small particles. The influences of PLA solvent type, PLA solution concentrations; the viscosity, electrical conductivity and surface tension of PLA solutions and PLA/BSA emulsions; and the applied voltage and flow rate on the morphology and size of the BSA-loaded PLA particles were examined. 1,2-dichloroethane (DCE) was a better solvent for PLA than dichloromethane. Spherical electrosprayed particles, with smooth surfaces, were observed with both solvents. The electrical conductivity increased and particle size decreased when acetone was mixed with DCE as PLA solvent. However, the particles were no longer spherical. The size of the particles increased and shape became spherical as PLA concentration was increased from 1-3%. Increasing the concentration to 4% resulted in the formation of a mixture of beads and fibres. Particle size decreased as applied voltage was increased from 10-15 kV and increased as flow rate was increased from 0.5-3 ml h(-1).
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PMID:Electrospray encapsulation of water-soluble protein with polylactide. I. Effects of formulations and process on morphology and particle size. 1683 Sep 78

We report a study evaluating the encapsulation and release modalities from poly(D,L lactic acid) (PLA) or poly(D,L-lactide-co-glicolide) (PLGA) micro- and nano-particles of the antiischemic drug N6-cyclopentyladenosine (CPA) and bovine serum albumin (BSA), chosen as protein model. The results obtained by classical preparation methods (nanoprecipitation, single or double emulsion/solvent evaporation) of the particles were compared with those obtained by their formulation with a novel method, employing a thermosensible gel of Pluronic F-127, whose aqueous solutions can be liquid when refrigerated, but gel upon warming. Our results indicate that CPA-loaded nanoparticles, obtained by classical methods, drastically reduce their drug content showing, moreover, any control of the drug release with respect to CPA-loaded microparticles. The novel preparation method allowed us to obtain, instead, CPA encapsulation values in nanoparticles similar to those obtained for microparticles, achieving also a weak control of the drug release. Any drastic reduction of BSA particle content was obtained by decreasing their size from micro- to nano-scales, independently on the employment of classical or novel preparation methods. Moreover, the size reduction induced only a weak increase of the BSA release rate. The patterns of protein released from micro- and nano-particles obtained by the same formulation method were similar. In particular, the micro- and nano-spheres prepared by double emulsion technique showed an incomplete BSA release, characterized by an elevated burst effect followed by a very slow phase. On the other hand, the release from micro- and nano-particles obtained by the novel method was complete and quite regular, being characterized by a little burst release followed by a fast phase. These results have been related to the strong BSA distribution (observed by confocal laser scanning microscope) in the surface or in the core of microparticles obtained by the classical or novel methods, respectively.
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PMID:Polymeric nanoparticles as drug controlled release systems: a new formulation strategy for drugs with small or large molecular weight. 1704 20

A novel mixed micelle that comprised of poly(N-isopropylacrylamide-co-methacrylic acid)-graft-poly(D,L-lactide) (P(NIPAAm-co-MAAc)-g-PLA) with methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PLA) was developed for application in cancer therapy. The mixed micelle had an multi-functional inner core of P(NIPAAm-co-MAAc)-g-PLA to enable intracellular drug delivery and an extended hydrophilic outer shell of mPEG to hide the inner core. Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicates that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of graft copolymer were efficiently screened by mPEG. From the drug release study, the mPEG-PLA diblock copolymer in mixed micelles slightly affected the functionalities of the P(NIPAAm-co-MAAc)-g-PLA graft copolymer; the graft copolymer still exhibited pH- and thermo-sensitivities in this core-shell structure. A change in pH deformed the structure of the inner core from that of aggregated P(NIPAAm-co-MAAc), causing the release of a significant quantity of doxorubicin (Dox) from mixed micelles. Clear differences between free Dox and Dox-mixed micelles were observed using confocal laser scanning microscopy (CLSM). This study presents not only a new micelle structure for a graft-diblock copolymer system, but also a method for overcoming some of the limitations on biomaterials used in intravenous injection.
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PMID:Mixed micelles formed from graft and diblock copolymers for application in intracellular drug delivery. 1709 28

Endothelial dysfunction (ED) in peritoneal dialysis patients plays pivotal role in progression of atherosclerosis and hemostasis disturbances. Malnutrition is one of the most important complication of PD. Both ED and malnutrition cause higher rate of cardiovascular events in these patients. 32 PD patients were analyzed. Endothelial function was assessed by measurements of serum level of vWF:Ag; t-Pa:Ag; TM:Ag. Nutritional status assessment included: body mass index-BMI, MAMC measurements; and serum albumin, total protein, prealbumin, transferrin, cholesterol, insulin, insulin like growth factor-1 (IGF-1). There were higher levels of vWF:Ag but lower of t-PA:Ag and TM:Ag after 12 month of observation. Serum levels of prealbumin, insulin, cholesterol were stable, but there were lower levels of albumin, IGF-1, and higher of transferrin at the end of the follow up. There were no differences in anthropometric indices during the follow up. We found statistically significant linear correlations: t-Pa:Ag vs prealbumin; t-Pa:Ag vs cholesterol; TM:Ag vs albumin. In the course of 12 months observation of peritoneal dialysis patients we found deterioration of endothelial function, expressed by evaluated endothelial antigens. Some correlations found in our study might express close relationship between endothelial function markers and nutritional status.
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PMID:[Endothelial dysfunction in peritoneal dialysis patients and its relationship to nutrition]. 1714 96

Stability of protein-encapsulating DRV (dried-rehydrated vesicle) liposomes is evaluated after freeze-drying vesicles in presence (or not) of trehalose. Two proteins, bovine serum albumin (BSA) and tissue-type plasminogen activator (t-PA), are used, and protein-encapsulating liposomes with different lipid compositions are prepared by DRV technique. Encapsulation efficiencies are calculated, after measuring BSA with a fluorescence technique and t-PA's amidolytic activity toward a chromogenic substrate. Experimental results show that encapsulation of BSA in vesicles ranges between 35 and 53% of the protein and is only slightly affected by lipid composition. For t-PA, entrapment efficiencies are lower, ranging between 2 and 16%, while lipid composition has substantial effect on entrapment (cholesterol inclusion is very important). After freeze-drying, some lipid compositions remain stable, retaining most of initially entrapped proteins, while others do not, but they may be stabilized by trehalose. In the case of BSA, liposome behavior cannot be explained based on lipid membrane rigidity (more rigid = more stable). This may be connected with previously demonstrated interactions of BSA with membranes. Oppositely, t-PA behavior is more predictable, meaning that the lipid composition selected for the specific therapeutic application determines the need for cryoprotectant addition before freeze-drying t-PA containing DRV liposomes, perhaps due to the fact that under conditions applying minimum or no interactions between t-PA and lipid membranes occur.Thereby, interactions between proteins and membranes determine not only the encapsulation efficiency but also the need for cryopreservation of liposomal protein formulations.
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PMID:Stability of protein-encapsulating DRV liposomes after freeze-drying: A study with BSA and t-PA. 1716 81

Cationic bovine serum albumin (CBSA) conjugated poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was designed as a novel drug carrier for brain delivery. In this paper, three formulations of CBSA-NP with different surface CBSA density as well as native bovine serum albumin conjugated nanoparticle (BSA-NP) and CBSA unconjugated pegylated nanoparticle (NP), were formulated. Their brain transcytosis across the blood-brain barrier (BBB) coculture and brain delivery in mice were investigated using 6-coumarin as fluorescent probe. By using free CBSA as specific inhibitor, it was evidenced that CBSA-NP crossed the brain capillary endothelium through absorptive mediated transcytosis. The result of transcytosis across the BBB coculture and brain delivery in mice proved that the increase of surface CBSA density of the nanoparticle enhanced the BBB permeability-surface area but decreased blood AUC. The optimized CBSA number conjugated per averaged nanoparticle was 110, with the maleimide-PEG-PLA/methoxy-PEG-PLA weight ratio 1:10, which can acquire the greatest percentage of injected dose per gram brain (%ID/g brain) by 2.3-fold compared with NP. Besides, "accelerated blood clearance phenomenon" was found through evaluating blood clearance profile of CBSA-NP post-injection of single dose or over a period of successive high doses of CBSA-NP. Understanding these issues is important for the future development of CBSA-NP as a brain delivery carrier and for the attenuation of toxicity or immunological responses to the nanodevice following a consequence of nanomedication.
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PMID:Brain delivery property and accelerated blood clearance of cationic albumin conjugated pegylated nanoparticle. 1724 Apr 71

Nanoparticles (NPs) of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers with various PLA:TPGS component ratios were prepared by the double emulsion technique for protein drug formulation with bovine serum albumin (BSA) as a model protein. Influence of the PLA:TPGS component ratio and the BSA loading level on the drug encapsulation efficiency (EE) and in vitro drug release behavior was investigated. The PLA-TPGS NPs achieved 16.7% protein drug loading and 75.6% EE, which exhibited a biphasic pattern of controlled protein release with higher initial burst for those NPs of more TPGS content. Furthermore, the released proteins retained good structural integrity for at least 35 days at 37 degrees C as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD) spectroscopy. Compared with other biodegradable polymeric NPs such as poly(D,L-lactide-co-glycolide) (PLGA) NPs, PLA-TPGS NPs could provide the encapsulated proteins a milder environment. Confocal laser scanning microscopy (CLSM) observation demonstrated the intracellular uptake of the PLA-TPGS NPs by NIH-3T3 fibroblast cells and Caco-2 cancer cells. This research suggests that PLA-TPGS NPs could be of great potential for clinical formulation of proteins and peptides.
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PMID:Nanoparticles of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers for protein drug delivery. 1725 Aug 86

In this study, the adsorption of amphiphilic poly(ethylene oxide)-block-polylactide (mPEO-PLA) copolymers from a selective solvent onto a polylactide surface was studied as a method of polylactide surface modification and its effect on nonspecific protein adsorption was evaluated. A series of well defined mPEO-PLA copolymers was prepared to investigate the effect of copolymer composition on the resulting PEO chain density and on the surface resistance to protein adsorption. The copolymers contained PEO blocks with molecular weights ranging between 5600 and 23,800 and with 16-47 wt% of PLA. The adsorption of both the copolymers and bovine serum albumin was quantified by attenuated total reflection FTIR spectroscopy (ATR-FTIR). In addition to the adsorbed copolymer amount, its actual composition was determined. The PEO chain density on the surface was found to decrease with the molecular weight of the PEO block and to increase with the molecular weight of the PLA block. The adsorbed copolymers displayed the ability to reduce protein adsorption. The maximum reduction within the tested series (by 80%) was achieved with the copolymer containing PEO of MW 5600 and a PLA block of the same MW.
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PMID:Adsorption of poly(ethylene oxide)-block-polylactide copolymers on polylactide as studied by ATR-FTIR spectroscopy. 1726 80


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