Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efficient and controlled gene delivery from biodegradable materials can be employed to stimulate cellular processes that lead to tissue regeneration. In this report, a substrate-mediated approach was developed to deliver DNA from hyaluronic acid-collagen hydrogels. The hydrogels were formed by crosslinking HA with poly(ethylene glycol) diglycidyl ether. Poly(ethylene imine)(PEI)/DNA complexes were immobilized to the substrate using either biotin/neutravidin or non-specific adsorption. Complexes were formed in the presence or absence of salt to regulate complex size, and resulted in complexes with z-average diameters of 1221.7 +/- 152.3 and 139.4 +/- 1.3 nm, respectively. During 48-h incubation in PBS or hyaluronidase, DNA was released slowly from the hydrogel substrate (<30% of immobilized DNA), which was enhanced by incubation with conditioned media (approximately 50% of immobilized DNA). Transgene expression mediated by immobilized, large diameter complexes was 3 to 7-fold greater than for small diameter complexes. However, the percentage of cells expressing the transgene was greater for small diameter complexes (48.7%) than for large diameter complexes (22.3%). Spatially controlled gene transfer was achieved by topographically patterning the hydrogel to pattern cell adhesion. Biomaterial-based gene delivery can be applicable to numerous tissue engineering applications, or as a tool to examine tissue formation.
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PMID:DNA delivery from hyaluronic acid-collagen hydrogels via a substrate-mediated approach. 1552 59

Elastin-like polymers (ELPs) are a new kind of protein-based polymers showing interesting properties in the biomaterial field. This work explored the use of self-assembled poly(VPAVG) micro- and nanoparticles as vehicles for the controlled release of the model drug dexamethasone phosphate (DMP). Poly(VPAVG) has shown to form stable particles with a size below 3 mum as a water or PBS polymer solution was warmed above its transition temperature ( approximately 30 degrees C). Due to the peculiar composition of the monomer, the formation and redissolution of the self-assembled microparticles shows an interesting hysteresis behaviour by which the particles are formed at this temperature but do not redissolve until a strong undercooling of approximately 12-15 degrees C is achieved. Therefore, the particles, once formed, are stable either at room or body temperature. These self-assembled particles are able to encapsulate significant amounts of the model drug when self-assembling was carried out in a co-solution polymer-DMP. The release profiles showed a sustained DMP release for about 30 days. Being the potential of this new polymeric carrier high, further research is being conducted to functionalise the poly(VPAVG) base as a way to induce a stronger polymer-drug binding and, accordingly, a more sustained release.
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PMID:Self-assembled particles of an elastin-like polymer as vehicles for controlled drug release. 1565 38

Poly(butylene succinate-co-butylene adipate) (PBSA)-degrading bacterium, strain 1-A, was isolated from soil. Strain 1-A was identified as Bacillus pumilus on the basis of its physiological properties and partial 16S rRNA gene sequence. Strain 1-A also degraded poly(butylene succinate) (PBS) and poly(epsilon-caprolactone). On the other hand, poly(butylene adipate terephthalate) and poly(lactic acid) were minimally degraded by strain 1-A. The NMR spectra of degradation products from PBSA indicated that the adipate units were more rapidly degraded than 1,4-butanediol and succinate units. This seems to be one of the reasons why strain 1-A degraded PBSA faster than PBS.
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PMID:Isolation and characterization of poly(butylene succinate-co-butylene adipate)-degrading microorganism. 1623 4

Poly(3-hydroxybutyrate) (P3HB), its co-polymers with 3-hydroxyvalerate (HV) (PHBV8 and PHBV22), and their hydroxyapatite (HAp) containing composites (5 and 15%, w/w) were prepared by injection molding. PHBV bone plates with low valerate contents and 15% (w/w) HAp appear to have better mechanical properties than the others. Flexural strengths of 15% (w/w) HAp-loaded P3HB, PHBV8 and PHBV22 were 78.28, 63.45 and 39.38 MPa, respectively. Tensile strengths of 15% (w/w) HAp-loaded P3HB, PHBV8 and PHBV22 were 18.99, 15.44 and 11.02 MPa, respectively. For the ageing test, bone plates were incubated in phosphate-buffered saline PBS (0.1 M, pH 7.4) at 37 degrees C and at pre-determined time points they were removed and subjected to a three-point bending test. Incubation in PBS caused a sharp decrease in the mechanical properties within the first 24 h, followed either by a gradual decrease or no change for a period of about 1 month. SEM results showed that there was no significant material erosion in the 4-week incubation period. P3HB loaded with 15% HAp appeared to yield the most suitable bone plate, insofar as mechanical properties are concerned with potential for further testing in vivo.
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PMID:Hydroxyapatite reinforced poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) based degradable composite bone plate. 1636 34

Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin-like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as "building blocks" in the natural elastin. This smart thermoresponsive polymer has the ability to self-associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind-paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection.
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PMID:Biocompatibility of elastin-like polymer poly(VPAVG) microparticles: in vitro and in vivo studies. 1664 66

Poly(L-lactic acid) (PLLA) has been used for fracture fixation devices, but its use is limited because of its poor biocompatibility and mechanical properties. The effects of extrusion, incorporation of hydroxyapatite (HA) and self-reinforced composites (SRCs) on the resultant mechanical properties of PLLA were examined. Samples were conditioned for up to 52 weeks in PBS at 37 degrees C. Extrusion did not adversely affect the mechanical properties of PLLA. After in vitro conditioning, a slight but significant reduction in the strain to failure and modulus was seen. HA (10-40%) by weight was evenly distributed into PLLA using an intermeshing twin-screw extruder. As ceramic content increased, the initial modulus increased but flexural strength decreased. After immersion, the modulus of all HA-PLLA blends was lower than PLLA. HA particles did not form a strong bond with the PLLA, which promoted easier degradation of the HA-PLLA matrix. SRCs showed a higher modulus and strength when compared to all materials except the modulus of 30 and 40% HA-PLLA composites before immersion. Water preferentially attacked the matrix of the composite, leading to more fiber pullout, but the fiber orientation maintained the advantages in strength and modulus up to 24 weeks in vitro.
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PMID:In vitro flexural properties of hydroxyapatite and self-reinforced poly(L-lactic acid). 1673 80

The aim of this work was to develop a stable injectable formulation of the antimalarial drug halofantrine (Hf) based on nanocapsules (NC) prepared from biodegradable polymers with Miglyol 810N as the oily core. Poly(D,L-lactide) PLA and its copolymers with poly(ethyleneglycol) (PLA-PEG) were used together with the surfactants poloxamer 188 and lecithin to yield NC with different surface properties. Highly efficient loading of the free base form of Hf was obtained; zeta potential measurements indicated that a part of the associated Hf was at the NC surface, interacting with the lecithin. NC were 150-250 nm in diameter and more stable on storage than nanoemulsions formed from oil and lecithin without polymer. The most stable NC, showing minimal size changes and flocculation, were those with a high density of 20-kDa PEG chains covalently grafted at the surface. Hf release from NC occurred mainly by partition with the external medium. In PBS, even when Tween 80 was added, release was limited to 20% of the total content, whatever the formulation. Addition of serum to the medium allowed complete and rapid release from PLA NC stabilized with adsorbed poloxamer 188, because of the high affinity of Hf for lipoproteins. However, the presence of covalently grafted PEG chains at the surface limited release by providing a hydrophilic steric barrier at the particle surface. A dense coverage with long PEG chains provided the best reduction of release. Such systems could constitute a long-circulating intravenous formulation of Hf for treating severe malaria.
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PMID:Surface-modified and conventional nanocapsules as novel formulations for parenteral delivery of halofantrine. 1704 36

This study aims to promote long-term retinal ganglion cell (RGC) survival in a spontaneous glaucoma model by injecting slow-release Poly(DL-lactide-co-glycolide) (PLGA) microspheres containing glial cell line-derived neurotrophic factor (GDNF) into the vitreous. Microspheres (1 microL) suspended in PBS were injected in ipsilateral eyes while contralateral eyes served as untreated controls. Mice were injected at 2 months intervals (1-4 injections) depending on the protocol. ELISA assay indicated a cumulative GDNF release of 35.4 ng/mg over 71 days. The release was nonlinear with an initial burst of over 50%. Mice displayed a 30% drop in RGC density by 8 months (p = 0.013) and 80% drop by 10 months (p < 0.01). GDNF delivery increased RGC survival in all groups. Mice receiving early treatment showed up to 3.5 times greater RGC density than untreated mice at 15 months survival (p < 0.05). No significant effect was found in sham or lens injury groups. Microsphere-delivered GDNF significantly increases long-term RGC survival in a spontaneous glaucoma model, although the nonlinear release kinetics suggest that burst release may play a role in this rescue. Neuroprotection with slow-release polymers with improved release kinetics should be further studied as a potential therapy for glaucoma and other diseases involving the loss of central nervous system neurons.
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PMID:Neuroprotection of retinal ganglion cells in DBA/2J mice with GDNF-loaded biodegradable microspheres. 1717 8

We developed a vector that might enable gene therapy of metabolic liver disease or hepatoma. Here we demonstrate the use of cationically modified biocompatible phospholipid polymer conjugated with hepatitis B surface (HBs) antigen for the specific transfer of genes into human hepatocytes. Poly(2-methacryloyloxyethyl phosphorylcholine (MPC)- co-N,N-dimethylaminoethyl methacrylate (DMAEMA)-co- p-nitrophenylcarbonyloxyethyl methacrylate(NPMA))(polyMDN) was prepared as a frame of vector. The specific expression of sFlt-1 or GFP by polyMDN conjugated with HBs containing plasmid (plasmid/polyMDN-HBs), polyMDN containing plasmid (plasmid/polyMDN), plasmid only and PBS were assessed in tumor cells (HepG2 or WiDr) in vitro and in vivo. The histological findings, organ weight changes, and degree of liver dysfunction were examined in the mice administered by several reagents. The sFlt-1 and GFP expression was observed only in the HepG2 cells transfected with sFlt-1 or GFP/polyMDN-HBs. None of the side effects mentioned above was observed. In conclusion, these results suggest that polyMDN-HBs is a human hepatocyte-specific gene delivery vector that might not have serious side effects.
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PMID:Development of gene vectors for pinpoint targeting to human hepatocytes by cationically modified polymer complexes. 1720 35

Fibroblast and macrophage are 2 dominant cell types respond cooperatively to degrade implanted biomaterials. Using an electrospun Dextran/Poly-lactide-co-glycolide (PLGA) scaffold as a model, an in vitro fibroblast/macrophage co-culture system was developed to investigate the degradability of implantable biodegradable materials. SEM showed that both fibroblasts and macrophages were able to degrade the scaffold, separately or cooperatively. Under the synergistic coordination of macrophages and fibroblasts, scaffolds showed faster degradation rate than their counterparts incubated with a single type of cells as well as in PBS or cell culture medium. Lysozyme, non-specific esterase (NSE), gelatinase, hyaluronidase-1 and alpha-glucosidase were up-regulated in the presence of the scaffold, suggesting their roles in the cell-mediated scaffold degradation. In addition, the expressions of cell surface receptors CD204 and Toll like receptor 4 (TLR4) were elevated 1 week after cell seeding, implying that these receptors might be involved in scaffold degradation. The results of in vivo subdermal implantation of the scaffold further confirmed the biodegradability of the Dextran/PLGA scaffold. The fibroblast/macrophage co-culture model adequately mimicked the in vivo environment and could be further developed into an in vitro tool for initial biomaterial evaluation.
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PMID:The biodegradability of electrospun Dextran/PLGA scaffold in a fibroblast/macrophage co-culture. 1819 3


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