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)

Arterial restenosis is responsible for the high failure rates of vascular reconstruction procedures. Local sustained drug delivery has shown promise in the prevention of restenosis. The drug release rate from mithramycin-loaded EVA matrices (0.1%) was evaluated, and their antirestenotic effect was studied in the rat carotid model and rabbit model of vascular grafts. The modulation of c-myc expression by mithramycin treatment was examined by immunohistochemistry in the rat carotid model. The proliferative response of injured rat arteries was studied by bromdeoxyuridine (BrdU) immunostaining. The impact of mithramycin treatment on vasomotor responses of the venous segments grafted into arterial circulation was studied ex vivo using vasoreactive compounds. Mithramycin was released exponentially from EVA matrices in PBS. Matrices co-formulated with PEG-4600 revealed enhanced release kinetics. The perivascular implantation of drug-loaded EVA-PEG matrices led to 50% reduction of neointimal formation, and reduced the c-myc expression and BrdU labeling in comparison to control implants. Decreased sensitivity of mithramycin-treated grafts to serotonin-induced vasoconstriction was observed. Local perivascular mithramycin treatment limits the functional alteration caused by the grafting of venous segments in high-pressure arterial environment, and potently inhibits stenosis secondary to grafting and angioplasty injury. The antirestenotic effect is associated with reduced c-myc expression and with subsequent decrease in SMC proliferation.
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PMID:Local delivery of mithramycin restores vascular reactivity and inhibits neointimal formation in injured arteries and vascular grafts. 1173 85

Antisense strategy is a promising approach for the prevention of in-stent restenosis if therapeutic agents such as antisense oligodeoxynucleotides (AS-ODNs) can be successfully delivered to the implant site. Optimizing the routes and conditions for controlled loading and release of therapeutic agents from a biocompatible polymer coating is still required. In this study, phosphorylcholine (PC) polymer films bearing different cationic charge densities were deposited onto smooth silicon substrates. The thickness of these films was determined by spectroscopic ellipsometry (SE). Human c-myc AS-ODNs were incorporated into the PC polymer films by immersion in concentrated AS-ODN solution and eluted into PBS under physiological conditions. The elution profile was monitored by UV spectrometry and gel electrophoresis. Cellular uptake of the eluted AS-ODN into vascular smooth muscle cells (VSMCs) was evaluated by fluorescence microscopy. The results showed that ODN loading capacities increased with film thickness and were also strongly dependent on the cationic charge density. AS-ODN release was characterized by a slight initial burst in the first half hour followed by a period of sustained release up to 8 days. Gel electrophoresis demonstrated DNA integrity, and different transfection efficiencies were observed when the eluted ODNs were transfected into VSMCs. These results demonstrated that cationically modified PC polymers are capable of delivery of antisense ODNs in a controlled manner and that they are well suited for specific biomedical devices such as DNA-eluting stents.
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PMID:Controlled delivery of antisense oligodeoxynucleotide from cationically modified phosphorylcholine polymer films. 1652 15

Fabrication of polymeric multilayered films based on the electrostatic self-assembly of polycations and polyanions is a promising approach for controlled loading and release in gene delivery. In this study, we have fabricated a series of multilayered films based on alternate deposition between positively-charged cationic phosphorylcholine copolymer (PC copolymer) and negatively-charged c-myc anti-sense oligodeoxynucleotide (AS-ODN). The growth of film thickness and increase of ODN loading capacity were monitored by spectroscopic ellipsometry (SE) and confocal laser scanning microscopy (CLSM). After elution into PBS buffer under physiological conditions, the elution profile was monitored by UV spectrometry and gel electrophoresis. Employing a secondary transgenic vector, the cellular uptake of the eluted AS-ODN into HeLa cells was evaluated by fluorescent microscopy and FACS analysis. The biological effect of eluted AS-ODN was evaluated by cell growth inhibition. The results showed that AS-ODN loading capacity increased almost linearly with the number of PC polymer/ODN bilayers and was also strongly dependent upon the cationic charge density. Through swelling, a non-degradable release mechanism, the AS-ODN release was characterized by two distinguishable release regimes: a fast release regime during the first 6 hour period and a slow release regime from 6 hour to the 8th day, both of which were characterized by zero-order kinetics. Gel electrophoresis showed excellent DNA integrity and strong transfection was observed when the eluted ODN was transfected into HeLa cells. Cell growth was significantly inhibited by eluted AS-ODN, indicating its full bioactivity. These results demonstrate that PC multilayered polymer films are capable of delivering a prescribed amount of anti-sense ODN with a controllable kinetic profile and that the multilayer process is more efficient and reliable than most other existing coating approaches largely based on single-layer fabrication.
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PMID:Controlled delivery of anti-sense oligodeoxynucleotide from multilayered biocompatible phosphorylcholine polymer films. 1856 37