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1.
Incorporation of nitric oxide (NO) donors in non-toxic polymeric matrices can be a useful strategy for allowing topical NO delivery. We have incorporated the NO-donor S-nitrosoglutathione (GSNO) into a liquid poly(ethylene glycol) (PEG)/H2O matrix through the S-nitrosation of GSH by a NO/O2 gas mixture. Kinetic measurements of GSNO decomposition associated with NO release were performed at 25, 35, and 45 degrees C in the dark and under irradiation with UV/Vis light, lambda>480 nm and lambda=333 nm. NO release from the liquid matrix to the gas phase was confirmed by mass spectrometry. The PEG/H2O matrix stabilizes GSNO leading to expressive reductions in the initial rates of thermal and photochemical NO release, compared to aqueous GSNO solution. This matrix effect is assigned to diffusional constrains imposed on the escape of the NO and GS radicals formed in the solvent cage. This effect allows the storage of PEG-GSNO formulations for extended periods (more than 65 days at freezer) with negligible decomposition. PEG-GSNO formulation seems therefore to be applicable in topical NO delivery and GSNO displays potential as a percutaneous absorption enhancer. Moreover, the rate of NO release can be locally increased by irradiation with visible light.  相似文献   

2.

Background

The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface.

Methods

Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions.

Results

Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation.

Conclusion

We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient.  相似文献   

3.
Drug‐eluting stents (DES) were developed to combat the problem of in‐stent restenosis, and evaluating the biological activity from DES systems is critical for its safety and efficacy. To test the cytotoxicity of nitric oxide (NO) donor‐containing polymers for their potential use in DES applications, S‐nitrosoglutathione (GSNO) or in combination with poly(vinyl alcohol) (PVA) and poly(vinyl pyrrolidone) (PVP) in an aqueous polymeric solution (PVA/PVP/GSNO) was investigated using Balb/c 3T3 and Rabbit arterial smooth muscle (RASM) cells. The sensitivity of 3T3 cells to the cytotoxicity effects induced by GSNO was higher than that of RASM cells, while RASM cells were more susceptible to alterations in membrane permeability. Cell growth assays showed that GSNO and PVA/PVP/GSNO induced antiproliferative effects in RASM cells. Moreover, the presence of polymers can reduce the cytotoxicity and enhance the antiproliferative effects of GSNO. Dose‐dependent inhibition of platelet aggregation was similar for both PVA/PVP/GSNO (EC50 of 3.4 ± 2.3 µM) and GSNO (EC50 of 2.8 ± 1.1 µM) solutions. Platelet adhesion assays showed that the inhibition caused by GSNO (EC50 of 5.0 mM) was dependent on the presence of plasma. These results demonstrate that the methodology adopted here is suitable to establish safety margins and evaluate the antithrombotic potential and antiproliferative effects of NO‐eluting biomaterials and polymeric solutions for the new cardiovascular devices, and also to emphasize the importance of using more specific cell lines in these evaluations. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

4.
Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.  相似文献   

5.
A method to correct stent related complications non-invasively, is the local delivery of therapeutic agents. Different drugs have been delivered on stents, after being either dispersed or encapsulated in polymeric materials, and placed on stents to form drug-eluting-stents (DE-stents). Investigation of possibility to cover polymer - coated metallic stents, with liposomal drugs, for preparation of novel DE-liposome-coated-stents, has been initiated few years ago. In this context our research has been focused on answering the following questions: (i) Can liposomes be applied as coatings on polymer covered stents? (ii) Can drug release from liposome coated-stents be controlled? And: (iii) how is haemo-compatibility of stents affected? The results of the experiments carried out demonstrate that liposomal formulations of drugs can be used as coating systems of polymer covered stents for achieving sustained release of drugs at the site of interest. By modifying liposome characteristics, different amounts of drugs may be placed on the stents and their release rates can be adjusted for maximum therapeutic benefit. Finally, haemocompatibility of stents is highly improved (mainly in terms of cell adhesion and activation of coagulation system), when stents are coated with heparin-encapsulating -DRV liposomes.  相似文献   

6.
Today the most popular approach for the prevention of the restenosis consists in the use of the drug eluting stents. The stent acts as a source of drug, from a coating or from a reservoir, which is transported into and through the artery wall. In this study, the behaviour of a model of a hydrophilic drug (heparin) released from a coronary stent into the arterial wall is investigated. The presence of the specific binding site action is modelled using a reversible chemical reaction that explains the prolonged presence of drug in the vascular tissue. An axi-symmetric model of a single stent strut is considered. First an advection-diffusion problem is solved using the finite element method. Then a simplified model with diffusion only in the arterial wall is compared with: (i) a model including the presence of reversible binding sites in the vascular wall and (ii) a model featuring a drug reservoir made of a degradable polymeric matrix. The results show that the inclusion of a reversible binding for the drug leads to delayed release curves and that the polymer erosion affects the drug release showing a quicker elution of the drug from the stent.  相似文献   

7.
Today the most popular approach for the prevention of the restenosis consists in the use of the drug eluting stents. The stent acts as a source of drug, from a coating or from a reservoir, which is transported into and through the artery wall. In this study, the behaviour of a model of a hydrophilic drug (heparin) released from a coronary stent into the arterial wall is investigated. The presence of the specific binding site action is modelled using a reversible chemical reaction that explains the prolonged presence of drug in the vascular tissue. An axi-symmetric model of a single stent strut is considered. First an advection–diffusion problem is solved using the finite element method. Then a simplified model with diffusion only in the arterial wall is compared with: (i) a model including the presence of reversible binding sites in the vascular wall and (ii) a model featuring a drug reservoir made of a degradable polymeric matrix. The results show that the inclusion of a reversible binding for the drug leads to delayed release curves and that the polymer erosion affects the drug release showing a quicker elution of the drug from the stent.  相似文献   

8.

Background and Aims

Since high-density lipoprotein (HDL) has pro-endothelial and anti-thrombotic effects, a HDL recruiting stent may prevent restenosis. In the present study we address the functional characteristics of an apolipoprotein A-I (ApoA-I) antibody coating in vitro. Subsequently, we tested its biological performance applied on stents in vivo in rabbits.

Materials and Methods

The impact of anti ApoA-I- versus apoB-antibody coated stainless steel discs were evaluated in vitro for endothelial cell adhesion, thrombin generation and platelet adhesion. In vivo, response to injury in the iliac artery of New Zealand white rabbits was used as read out comparing apoA-I-coated versus bare metal stents.

Results

ApoA-I antibody coated metal discs showed increased endothelial cell adhesion and proliferation and decreased thrombin generation and platelet adhesion, compared to control discs. In vivo, no difference was observed between ApoA-I and BMS stents in lumen stenosis (23.3±13.8% versus 23.3±11.3%, p=0.77) or intima surface area (0.81±0.62 mm2 vs 0.84±0.55 mm2, p=0.85). Immunohistochemistry also revealed no differences in cell proliferation, fibrin deposition, inflammation and endothelialization.

Conclusion

ApoA-I antibody coating has potent pro-endothelial and anti-thrombotic effects in vitro, but failed to enhance stent performance in a balloon injury rabbit model in vivo.  相似文献   

9.
The introduction of the drug-eluting stent (DES) proved to be an important step forward in reducing the rates of restenosis and target lesion revascularization after percutaneous coronary intervention (PCI). However, the rapid implementation of DES in standard practice and the expansion of the indications for PCI to high-risk patients and complex lesions also introduced a new problem. DES in-stent restenosis (ISR) occurs in 3 ?? 20% of patients, depending on the patient, lesion characteristics and the DES type. The initial commercially available DES used a stainless steel platform coated with a permanent polymer to provide a controlled release of an anti-restenotic drug. The platform, polymer and drug are all targets for improvement. More advanced metallic and fully biodegradable stent platforms are currently under investigation. The permanent polymer coating, a likely contributor to adverse events, is being superseded by biocompatible and bioabsorbable alternatives. New drugs and drug combinations are also a research goal, as interventional cardiologists and the industry strive towards a safer anti-restenotic DES. This paper reviews the benefits, risks, and current status of biodegradable drug-eluting stents.  相似文献   

10.
In-stent restenosis occurs in coronary arteries after implantation of drug-eluting stents with non-uniform restenosis thickness distribution in the artery cross section. Knowledge of the spatio-temporal drug uptake in the arterial wall is useful for investigating restenosis growth but may often be very expensive/difficult to acquire experimentally. In this study, local delivery of a hydrophobic drug from a drug-eluting stent implanted in a coronary artery is mathematically modelled to investigate the drug release and spatio-temporal drug distribution in the arterial wall. The model integrates drug diffusion in the coating and drug diffusion with reversible binding in the arterial wall. The model is solved by the finite volume method for both high and low drug loadings relative to its solubility in the stent coating with varied isotropic–anisotropic vascular drug diffusivities. Drug release profiles in the coating are observed to depend not only on the coating drug diffusivity but also on the properties of the surrounding arterial wall. Time dependencies of the spatially averaged free- and bound-drug levels in the arterial wall on the coating and vascular drug diffusivities are discussed. Anisotropic vascular drug diffusivities result in slightly different average drug levels in the arterial wall but with very different spatial distributions. Higher circumferential vascular diffusivity results in more uniform drug loading in the upper layers and is potentially beneficial in reducing in-stent restenosis. An analytical expression is derived which can be used to determine regions in the arterial with higher free-drug concentration than bound-drug concentration.  相似文献   

11.
药物洗脱支架(DES)在冠状动脉疾病的治疗中起到巨大作用,不但能机械支撑血管狭窄区,而且可以通过持续释放药物显著降低病灶处再狭窄率。然而,长期临床研究表明,载药DES在后期有引发血栓的风险。在DES表面载入基因药物,通过表面涂层输送系统局部缓慢释放治疗基因,能针对引起再狭窄的细胞过程进行修改。选择合适的治疗基因,可以抑制内膜增生,促进再内皮化,提高洗脱支架的有效性和安全性,是非常有前途的抗再狭窄方法。同时,良好的涂层材料不仅改善了支架表面的生物相容性,更能通过不同的基因药物输送系统有效控制治疗基因的释放速率。本文首先介绍了一部分针对再狭窄的治疗基因,在此基础上,综合阐述了基因缓释系统中使用的材料和技术,分析提炼了基因缓释系统的释放机理,举例分析了载基因洗脱支架的研究进展,并展望了该领域的发展前景。  相似文献   

12.
Clinical studies suggest that stent design and surface texture are responsible for differences in biocompatibility of metallic endovascular stents. A simple in vitro experimental setup was established to test stent-induced degree of platelet and leukocyte activation and platelet-leukocyte aggregation by flow cytometry. Heparin-coated tantalum stents and gold-coated and uncoated stainless steel stents were tested. Stents were implanted into silicone tubes and exposed to blood from healthy volunteers. Platelet and leukocyte activation and percentage of leukocyte-platelet aggregates were determined in a whole-blood assay by subsequent staining for activation-associated antigens (CD41a, CD42b, CD62p, and fibrinogen binding) and leukocyte antigens (CD14 and CD45) and flow cytometric analysis. Blood taken directly after venous puncture or exposed to the silicone tube alone was used as negative controls. Positive control was in vitro stimulation with thrombin receptor activating peptide (TRAP-6). Low degree of platelet activation and significant increase in monocyte- and neutrophil-platelet aggregation were observed in blood exposed to stents (P < 0.05). In addition, leukocyte activation was induced as measured by increased CD45 and CD14 expression. Heparin coated stents continuously induced less platelet activation and leukocyte-platelet aggregation than uncoated stainless steel stents of the same length and shorter stents of the same structure. Stent surface coating and texture plays a role in platelet and leukocyte activation and leukocyte-platelet aggregation. Using this simple in vitro assay and whole blood and flow cytometry, it seems possible to differentiate stents by their potency to activate platelets and/or leukocytes. This assay could be applied for improving the biocompatibility of coronary stents.  相似文献   

13.
Materials that permit control over the release of DNA from the surfaces of topologically complex implantable devices, such as intravascular stents, could contribute to the development of new approaches to the localized delivery of DNA. We report the fabrication of ultrathin, multilayered polyelectrolyte films that permit both the immobilization and controlled release of plasmid DNA from the surfaces of stainless steel intravascular stents. Our approach makes use of an aqueous-based, layer-by-layer method for the assembly of nanostructured thin films consisting of alternating layers of plasmid DNA and a hydrolytically degradable polyamine. Characterization of coated stents using scanning electron microscopy (SEM) demonstrated that stents were coated uniformly with an ultrathin film ca. 120 nm thick that adhered conformally to the surfaces of stent struts. These ultrathin films did not crack, peel, or delaminate substantially from the surface after exposure to a range of mechanical challenges representative of those encountered during stent deployment (e.g., balloon expansion). Stents coated with eight bilayers of degradable polyamine and a plasmid encoding enhanced green fluorescent protein (EGFP) sustained the release of DNA into solution for up to four days when incubated in phosphate buffered saline at 37 degrees C, and coated stents were capable of mediating the expression of EGFP in a mammalian cell line without the aid of additional transfection agents. The approach reported here could, with further development, contribute to the development of localized gene-based approaches to the treatment of cardiovascular diseases or related conditions.  相似文献   

14.
Synthetic polymers, like methacrylate (MA) compounds, have been clinically introduced as inert coatings to locally deliver drugs that inhibit restenosis after stent. The aim of the present study was to evaluate the effects of MA coating alone on vascular smooth muscle cell (VSMC) growth in vitro. Stainless steel stents were coated with MA at the following doses: 0.3, 1.5, and 3 ml. Uncoated/bare metal stents were used as controls. VSMCs were cultured in dishes, and a MA-coated stent or an uncoated bare metal stent was gently added to each well. VSMC proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Apoptosis was analyzed by three distinct approaches: 1) annexin V/propidium iodide fluorescence detection; 2) DNA laddering; and 3) caspase-3 activation and PARP cleavage. MA-coated stents induced a significant decrease of BrdU incorporation compared with uncoated stents at both the low and high concentrations. In VSMCs incubated with MA-coated stents, annexin V/propidium iodide fluorescence detection showed a significant increase in apoptotic cells, which was corroborated by the typical DNA laddering. Apoptosis of VSMCs after incubation with MA-coated stents was characterized by caspase-3 activation and PARP cleavage. The MA-coated stent induced VSMC growth arrest by inducing apoptosis in a dose-dependent manner. Thus MA is not an inert platform for eluting drugs because it is biologically active per se. This effect should be taken in account when evaluating an association of this coating with antiproliferative agents for in-stent restenosis prevention.  相似文献   

15.
A new biomimetic material for artificial blood vessel with in situ catalytic generation of nitric oxide(NO) was prepared in this study. Organoselenium immobilized polyethyleneimine as NO donor catalyst and sodium alginate were alternately loaded onto the surface of electrospun polycaprolactone matrix via electrostatic layer-by-layer self-assembly. This material revealed significant NO generation when contacting NO donor S-nitrosoglutathione(GSNO). Adhesion and spreading of smooth muscle cells were inhibited on this material in the presence of GSNO, while proliferation of endothelial cells was promoted. In vitro platelet adhesion and arteriovenous shunt experiments demonstrated good antithrombotic properties of this material, with inhibited platelet activation and aggregation, and prevention of acute thrombosis. This study may provide a new method of improving cellular function and antithrombotic property of vascular grafts.  相似文献   

16.
AIMS: The BiodivYsio trade mark stent (Biocompatibles Ltd, Farnham, UK) is coated with a phosphorylcholine (PC)-containing copolymer to confer biocompatibility. The SOPHOS (Study Of PHosphorylcholine coating On Stents) study was designed to assess the safety and efficacy of this novel coronary stent and by indirect comparison to indicate equivalence with other formal stent studies. METHODS AND RESULTS: Patients with angina and a single short (#x2A7F;12 mm) de novo lesion in a native coronary artery of >/=2.75 mm diameter were included. A total of 425 patients were allocated in 24 centers. Clinical data were collected at one-, six- and nine-month follow-up. Angiography was performed before and after the stent implantation. In addition, in the first 200 patients (SOPHOS A) angiography was routinely performed at six months. The following 225 patients (SOPHOS B) were merely followed up clinically. The primary end-point of the study, the six-month MACE-rate (MACE = Major Adverse Cardiac Events) was 13.4% (two cardiac death; five Q-wave/nine non-Q-wave myocardial infarctions (MI); nine CABG and 32 target lesion revascularization (TLR), which is similar to the calculated 15% MACE-rate in comparable reference studies. Secondary end-points included among others restenosis at six months in the SOPHOS A population. The target vessel diameter was 2.98 +/- 0.48 mm. Minimal lumen diameter pre/post procedure and at follow-up was 1.00 +/- 0.32, 2.69 +/- 0.37, 1.91 +/- 0.71 mm, respectively. The binary restenosis rate (>/=50% diameter stenosis at follow-up) was 17.7%. CONCLUSION: The coronary BiodivYsio stent is safe and effective as a primary device for the treatment of native coronary artery lesions in patients with stable or unstable angina pectoris. Clinical and angiographic results are in the statistical range of equivalence with comparable studies with other current stents.  相似文献   

17.
We examined the influence of S-nitrosoglutathione (GSNO) on alpha(IIb)beta(3) integrin-mediated platelet adhesion to immobilised fibrinogen. GSNO induced a time- and concentration-dependent inhibition of platelet adhesion. Inhibition was cGMP-independent and associated with both reduced platelet spreading and protein tyrosine phosphorylation. To investigate the cGMP-independent effects of NO we evaluated integrin beta(3) phosphorylation. Adhesion to fibrinogen induced rapid phosphorylation of beta(3) on tyrosines 773 and 785, which was reduced by GSNO in a cGMP independent manner. Similar results were observed in suspended platelets indicating that NO-induced effects were independent of spreading-induced signalling. This is the first demonstration that NO directly regulates integrin beta(3) phosphorylation.  相似文献   

18.
Implantation of stents into stenosed arteries helps to restore normal blood flow in ischemic organs. However, limited biocompatibility of the applied medical steel can cause acute thrombosis and long-term restenosis. Adhesion of monocytes to stent metal may participate in those acute and long-term complications of stent placement. Based on described prominent electrochemical properties of the interaction between the monocyte integrin receptor Mac-1 and its various ligands, we hypothesized, that this receptor is a central mediator of monocyte adhesion to stent metal and that semiconductor coating of medical steel reduces monocyte adhesion. Adhesion of monocytes on L-316 stainless steel was directly evaluated by light microscopy. Mac-1 could be identified as mediator of monocyte adhesion, since cell adhesion could be blocked by anti-Mac-1-antibodies, including the cross-reacting anti-GPIIb/IIIa antibody fragment abciximab. To further prove the central role of Mac-1, two CHO cell lines were generated expressing recombinant Mac-1 either as wild type, resulting in a low affinity receptor, or mutant with a GFFKR deletion of the alpha(M) subunit, resulting in a high affinity receptor. Indeed, adhesion was specific for Mac-1 and dependent on the affinity state of this integrin. Finally, we could demonstrate that Mac-1-mediated adhesion of monocytes to stents can be significantly inhibited by silicon carbide coating of the stent metal. In conclusion, the integrin Mac-1 and its affinity state could be identified as major mediators of monocyte adhesion on medical steel. As therapeutic strategies, the blockade of Mac-1 by antibodies or silicon carbide coating of steel inhibits monocyte adhesion on stents.  相似文献   

19.
Despite technical and mechanical improvement in coronary stents the incidence of restenosis caused by in-stent neointimal hyperplasia remains high. Oral administration of numerous pharmacological agents has failed to reduce restenosis after coronary stenting in humans, possibly owing to insufficient local drug concentration. Therefore, drug-eluting stents were developed as a vehicle for local drug administration. The authors developed a new drug-eluting polymer stent that is made of poly-l-lactic acid polymer mixed with tranilast, an anti-allergic drug that inhibits the migration and proliferation of vascular smooth muscle cells induced by platelet-derived growth factor and transforming growth factor->1. Polymer stents might be superior to polymer-coated metallic stents as local drug delivery stents in terms of biodegradation and the amount of loaded drug. Drug-mixed polymer stents can be loaded with a larger amount of drug than can drug-coated metallic stents because the polymer stent struts can contain the drug. Clinical application is required to assess the safety and efficacy of drug-eluting polymer stents against stent restenosis.  相似文献   

20.
Polyisobutylene (PIB)-based block copolymers have attracted significant interest as biomaterials. Poly(styrene-b-isobutylene-b-styrene) (SIBS) has been shown to be vascularly compatible and, when loaded with paclitaxel (PTx) and coated on a coronary stent, has the ability to deliver the drug directly to arterial walls. Modulation of drug release from this polymer has been achieved by varying the drug/polymer ratio, by blending SIBS with other polymers, and by derivatizing the styrene end blocks to vary the hydrophilicity of the copolymer. In this paper, results are reported on the synthesis, physical properties, and drug elution profile of PIB-based block copolymers containing methacrylate end blocks. The preparation of PIB-poly(alkyl methacrylate) block copolymers has been accomplished by a new synthetic methodology using living cationic and anionic polymerization techniques. 1,1-Diphenylethylene end-functionalized PIB was prepared from the reaction of living PIB and 1,4-bis(1-phenylethenyl)benzene, followed by the methylation of the resulting diphenyl carbenium ion with dimethylzinc (Zn(CH(3))(2)). PIB-DPE was quantitatively metalated with n-butyllithium in tetrahydrofuran, and the resulting macroinitiator could initiate the polymerization of methacrylate monomers, yielding block copolymers with high blocking efficiency. Poly(methyl methacrylate-b-isobutylene-b-methyl methacrylate) (PMMA-b-PIB-b-PMMA) and poly(hydroxyethyl methacrylate-b-isobutylene-b-hydroxyethyl methacrylate) (PHEMA-b-PIB-b-PHEMA) triblock copolymers were synthesized and used as drug delivery matrixes for coatings on coronary stents. The PMMA-b-PIB-b-PMMA/PTx system displayed zero-order drug release, while stents coated with PHEMA-b-PIB-b-PHEMA/PTx formulations exhibited a significant initial burst release of PTx. Physical characterization using atomic force microscopy and differential scanning calorimetry of the formulated PMMA-b-PIB-b-PMMA coating matrix indicated the partial miscibility of PTx with the PMMA microphase of the matrix.  相似文献   

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