涂层工艺对聚碳酸亚乙酯载药涂层性能和体外释放动力学的影响

为了考察不同涂层工艺对冠脉支架涂层的影响,分别采用手动浸涂和自动超声喷涂法在316L不锈钢冠脉支架基体表面制备含雷帕霉素的聚碳酸亚乙酯(PEC)涂层。首先对PEC进行了凝胶渗透色谱(GPC)、差示扫描量热(DSC)以及拉伸实验测试,初步证明其物理化学性质适合作支架可降解涂层材料。然后用扫描电子显微镜(SEM)、原子力显微镜(AFM)、接触角测定仪、球囊扩张法等对涂层表面的形貌、亲水性以及涂层和支架基体的结合力进行分析,并在PBS(pH=7.4)模拟体液中测试上述两种工艺方法制备的药物洗脱支架体外药物释放动力学曲线。结果表明,上述两种方法制备的药物涂层在微观结构、亲水性以及与支架的结合力方面存在一定差异,药物释放速率和释放趋势也有所不同,超声喷涂法制备的药物洗脱支架释放速率和释放趋势较稳定。     

聚碳酸亚丙亚乙酯冠脉支架涂层的制备和性能

以戊二酸锌为催化剂合成可降解聚碳酸亚丙亚乙酯(PPEC,MW=229.338kDa)并首次将其作为载药涂层材料进行研究。核磁共振氢谱(1 H NMR)显示分子链中环氧乙烷和环氧丙烷的贡献与原料中两者配比相同,碳酸酯段含量为76.7%。差示扫描量热仪(DSC)测得玻璃化转变温度(Tg)为16.8℃。拉伸实验得到断裂伸长率为550%。衰减全反射-傅立叶变换红外光谱(ATR-FT-IR)显示药物涂层中PPEC和雷帕霉素之间没有发生明显的化学反应。球囊扩张实验后用扫描电子显微镜(SEM)观察到药物涂层支架表面完整光滑,没有剥落翘起的现象。药物洗脱支架在模拟体液(PBS,pH值=7.4)中药物释放时间超过60d,速率由快变慢。实验表明PPEC作为支架涂层材料具有广阔的应用前景。     

镁合金支架双重可控释放涂层的制备及药物释放性能研究

在镁合金支架材料WE42表面制备了双重可控腐蚀和药物缓释涂层,并对其药物释放性能进行了研究.DSC研究表明紫杉醇均匀分散在PLGA体系中.药物释放实验表明,PLGA可使紫杉醇长期持续释放,突释较弱,释放是由扩散-降解控制.随载药膜中PEG分子量和含量的增加,药物释放率增加.外层明胶涂层能有效降低药物释放率,延长药物释放时间.     

碳纤维表面BN涂层的制备和表征

采用溶液浸涂法,添加聚乙烯醇作为中间转换物,在碳纤维表面制备了氮化硼涂层。采用SEM、FT-IR、XPS、TGA等测试技术对涂层的成分、结构、形貌进行了表征。实验结果表明,纤维表面没有开裂剥落,涂层与碳纤维结合良好,涂层碳纤维热稳定性良好,B和N的原子分数分别为15.69%和16.97%,hBN涂层的纯度较高。     

屏蔽层对支架涂层药物缓释影响的体外研究

载药涂层的药物释放行为对于药物洗脱支架的临床治疗效果具有非常重要的意义。讨论了在聚碳酸酯载药涂层外面再加一层空白聚合物层(即屏蔽层)对药物释放的影响。从4方面的体外实验证明屏蔽层(drug free polymer layer,DFPL)可以防止聚碳酸酯载药涂层药物"暴释"的现象,并且屏蔽层厚度和释放速率不是简单的比例关系,以及不同的药物梯度和不同的屏蔽层材料对药物释放有不同的影响效果。     

冠脉支架表面载药涂层的制备和性能

采用溶液聚合法制备了改性的聚甲基丙烯酸树脂,作为支架表面载药涂层的药物载体聚合物.采用浸涂法制备了不锈钢基体表面聚合物及聚合物载药涂层,并利用红外光谱及核磁共振波谱分析了所制备共聚物的成分,并评价了物理性能、生物稳定性能以及药物的释放性能.结果表明,所制备的涂层具有较好的生物稳定性,甲基丙烯酸和甲基丙烯酸丁酯的加入提高了聚合物的物理性能,尤其是涂层与金属基体的结合力所制备的药物释放涂层具有缓释紫杉醇的功能,其释放周期超过15 d.聚甲基丙烯酸树脂携带紫杉醇的载药涂层在生物稳定性、物理性能及药物释放性能方面满足冠脉支架的表面涂层的使用要求.     

可降解镁合金表面载药涂层的制备和性能

在可降解AZ31B镁合金心血管支架表面成功制备了携带雷帕霉素的聚乳酸-聚三亚甲基碳酸酯(PLA-PTMC)共聚物涂层,评价了涂层的表面形貌、降解性能、血液相容性和药物释放性能.结果表明,PLA-PTMC共聚物作为载药涂层具有良好的柔韧性,表面均匀、光滑,降解周期超过1个月,血液相容性良好.涂层具有缓释雷帕霉素的功能,释药周期超过1个月,可在内膜增生期内有效抑制支架植入后再狭窄的发生,满足冠脉支架表面载药层的使用要求.     

药物洗脱支架载药层材料及其制备技术研究进展

支架内再狭窄多年来一直是制约冠心病介入治疗远期疗效的瓶颈,药物洗脱支架的出现为解决这一问题提供了有效手段,而药物洗脱支架制备的关键在于载药层的制备.针对载药层制备技术,包括支架的预处理、载药材料的选择、载药层的制备工艺以及载药层药物的释放机制进行了回顾与综合评述,并指出了药物洗脱支架栽药层材料及其制备技术的发展方向.     

功能化二硫化钼纳米载药复合物的制备及体外药物释放研究

采用二硫化钼(MoS_2)表面接枝硫辛酸(LA)修饰的聚乙二醇(PEG)(LA-PEG),以增加其生物相容性,进一步接枝聚乙烯亚胺(PEI),用以连接牛血清蛋白(BSA)修饰的叶酸(FA),构建主动靶向体系叶酸-牛血清蛋白-聚乙烯亚胺-硫辛酸-二硫化钼-硫辛酸-聚乙二醇(FA-BSA-PEI-LA-MoS_2-LA-PEG),并对产物的形貌及理化性质进行测试。研究结果表明,制得的产物的水动力学直径约133nm,适合用作抗癌药物载体,以阿霉素(DOX)为模型药物,研究产物的载药能力和体外药物释放行为,在pH=5.0,近红外光照射条件下,经过68h,产物负载的DOX的累计释放量为67.8%,具有良好的载药能力和应用价值。     

可控降解抗感染材料的体外释药机制研究

在前期合成并表征了可控降解抗感染材料环丙沙星聚氨酯（CFPU）的基础上,建立高效液相色谱法（HPLC）测定其体外降解释放抗菌药物环丙沙星的含量;通过制作累积药物释放曲线,考察不同降解介质及其浓度对药物释放的影响;并对累积药物释放曲线进行拟合,研究其体外可控降解的药物释放机制。结果表明建立的HPLC法简单准确可靠。该材料的降解具有生物响应性,且符合一级动力学;药物释放是以Ritger-Pappas方程（0.45     

Dissolution rate enhancement,in vitro evaluation and investigation of drug release kinetics of chloramphenicol and sulphamethoxazole solid dispersions

Formulation of solid dispersions is one of the effective methods to increase the rate of solubilization and dissolution of poorly soluble drugs. Solid dispersions of chloramphenicol (CP) and sulphamethoxazole (SX) as model drugs were prepared by melt fusion method using polyethylene glycol 8000 (PEG 8000) as an inert carrier. The dissolution rate of CP and SX were rapid from solid dispersions with low drug and high polymer content. Characterization was performed using fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). FTIR analysis for the solid dispersions of CP and SX showed that there was no interaction between PEG 8000 and the drugs. Hyper-DSC studies revealed that CP and SX were converted into an amorphous form when formulated as solid dispersion in PEG 8000. Mathematical analysis of the release kinetics demonstrated that drug release from the various formulations followed different mechanisms. Permeability studies demonstrated that both CP and SX when formulated as solid dispersions showed enhanced permeability across Caco-2 cells and CP can be classified as well-absorbed compound when formulated as solid dispersions.     

Comparing the mucoadhesivity and drug release mechanisms of various polymer-containing propranolol buccal tablets

The aims were to compare the mucoadhesivity, controlled release properties, and release mechanisms of several polymeric systems of propranolol buccal tablets and to propose polymer(s) for formulation optimization. Mucoadhesivity differences in the polymer ranking between compacts and tablets were found. Mathematical models that best described the matrices were power law or a combination of the power law and Hopfenberg models. Poly acrylic acid (PAA), carboxymethyl cellulose (CMC), and poly ethylene glycol (PEG) in combination, were identified as suitable polymers for formulation optimization of a multipolymeric propranolol buccal tablet. Artificial neural networks were employed as a confirmatory approach to explicate that the selected polymers, in particular PAA, produced the most significant effect on the mean dissolution time and mucoadhesivity.     

Mechanistic analysis of drug release from theophylline pellets coated by films containing pectin, chitosan and Eudragit RS

The objective of this study was to obtain detailed information on the mechanism of drug release from mixed-film of pectin-chitosan/Eudragit® RS. Pellets (710-840 μm in diameter) containing 60% theophylline and 40% microcrystalline cellulose were prepared by extrusion-spheronization method. Eudragit® L100-55 enteric coating capsules included film-coated pellets of theophylline in theoretical coating weight gains of 10, 15, and 20%, with pectin-chitosan complex contents of 5, 10, 15, and 20% for each level of weight gain were prepared and subjected to in vitro drug release. Drug release from this system showed a bimodal release profile characteristic with the drug release enhancement, being triggered (burst release) in the colonic medium. The reason for burst drug release may be due to the enzymatic degradation of pectin via pectinolytic enzymes in the simulated colonic medium. The mechanism of drug release from each formulation was evaluated in the terms of zero-order, first-order, Higuchi and Korsmeyer-Peppas models. It was observed that none of the enteric coating capsules showed any drug release in the simulated gastric medium (phase I). The analysis of release profiles showed that zero-order kinetics was found as the better fitting model for all formulations in the simulated small intestine (phase II) and it could be due to the pectin-chitosan swelling and subsequent formation of aqueous channels. In the colonic medium (phase III), due to degradation of pectin and its leaching from the mixed-film, there was a modification in drug release kinetics from swelling-controlled at phase II to anomalous at phase III. It also was found that both zero-order and Higuchi models contributed in colonic drug release from most of the formulations.     

他克莫司-聚三亚甲基碳酸酯药物洗脱支架涂层研究

以表面溶蚀性可降解聚合物聚三亚甲基碳酸酯（PTMC）为载体,分别采用超声雾化喷涂技术和溶液浇注法制备了以PTMC为涂层载体的他克莫司药物洗脱支架和载药薄膜。傅里叶红外光谱（FT-IR）结果显示他克莫司分散在PTMC中。扫描电子显微镜观察支架撑开后的药物涂层保持连续均匀,没有开裂和剥落。他克莫司洗脱支架的药物释放行为与Weibull模型的相关性最高。体外血小板粘附和平滑肌粘附、增殖实验表明包载他克莫司的PTMC表面具有显著地抑制血小板粘附和平滑肌增生的作用。     

Standardized in vitro drug release test for colloidal drug carriers using modified USP dissolution apparatus I

Background: Recently the use of colloidal carriers as drug delivery systems is gaining more attention. Evaluation of the in vitro drug release is considered an important step during the development and quality control of such systems. Therefore, there is a need for a standard test technique to study in vitro drug release from colloidal systems. Methods: The glass basket dialysis method was performed by a modification to the USP dissolution apparatus I by replacing the baskets with glass cylinders closed at the lower end by dialysis membrane. This method was characterized for the essential test parameters and compared to the dialysis bags technique using different types of colloidal drug carriers, namely liposomes, polymeric, and lipid nanoparticles. Results: The method proved to be more discriminating than the conventional dialysis bag method and allowed for better comparison between different formulation parameters or experimental conditions. In general, the design is easy to perform, simple, and available in all pharmaceutical laboratories under the same setup. Conclusion: The described method is a step toward standardized dissolution tests on colloidal drug delivery systems and the possible comparability of results.     

The impact of preparation parameters on typical attributes of chitosan-heparin nanohydrogels: particle size,loading efficiency,and drug release

Today, developing an optimized nanoparticle (NP) preparation procedure is of paramount importance in all nanoparticulate drug delivery researches, leading to expanding more operative and clinically validated nanomedicines. In this study, a one-at-a-time experimental approach was used for evaluating the effect of various preparation factors on size, loading, and drug release of hydrogel NPs prepared with ionotropic gelation between heparin and chitosan. The size, loading efficiency (LE) and drug release profile of the NPs were evaluated when the chitosan molecular weight, chitosan concentration, heparin addition time to chitosan solution, heparin concentration, pH value of chitosan solution, temperature, and mixing rate were changed separately while other factors were in optimum condition. The results displayed that size and LE are highly influenced by chitosan concentration, getting an optimum of 63?±?0.57 and 75.19?±?2.65, respectively, when chitosan concentration was 0.75?mg/ml. Besides, heparin addition time of 3?min leaded to 74.1?±?0.79 % LE with no sensible effect on size and release profile. In addition, pH 5.5 showed a minimum size of 63?±?1.87, maximum LE of 73.81?±?3.13 and the slowest drug release with 63.71?±?3.84 % during one week. Although LE was not affected by temperature, size and release reduced to 63?±?0 and 74.21?±?1.99% when temperature increased from 25°C to 55°C. Also, continuous increase of mixer rate from 500 to 3500?rpm resulted in constant enhancement of LE from 58.3?±?3.6 to 74.4?±?2.59 as well as remarkable decrease in size from 148?±?4.88 to 63?±?2.64.     

Influence of soluble and insoluble cyclodextrin polymers on drug release from hydroxypropyl methylcellulose tablets

Background: The influence of β-cyclodextrin (β-CD) polymers on drug release from hydroxypropyl methylcellulose (HPMC) matrices has not been reported in the literature. Aim: The influence of monomeric β-CD and both soluble and insoluble β‐CD polymers on drug release from tablets containing either 30% or 50% hydroxypropyl methylcellulose has been studied using diflunisal (DF) as model drug. Method: The DF-β-CD inclusion complex (1:1 M) was prepared by coevaporation and characterised using X-ray diffraction, differential thermal analysis, and IR spectroscopy. The dissolution assays were performed according to the USP paddle method. Results: The incorporation of β-CD in the complexed form increases drug release from hydroxypropyl methylcellulose tablets in comparison with the physical mixture because of the better solubilization of the drug. The soluble polymer promotes drug release to a higher extent than the physical mixture with monomeric β-CD, but the insoluble polymer, which is itself a hydrogel, gives rise to the most retarded release profile, probably by retention of the drug in its structure. The formulations containing physical mixtures with either β‐CD or the soluble polymer present an optimum adjustment to zero-order release kinetics, and the inclusion complex followed non-Fickian diffusion according to the Korsmeyer–Peppas model. Conclusion: The release profile of DF from a HPMC matrix can be modulated in different ways by the use of either monomeric or polymeric β-CD.     

Hydrogel containing dexamethasone-loaded nanocapsules for cutaneous administration: preparation,characterization, and in vitro drug release study

Context: Our group previously reported the development of dexamethasone-loaded polymeric nanocapsules as an alternative for topical dermatological treatments. Objective: Our study aimed to prepare and characterize a hydrogel containing this system to improve the effectiveness of the glucocorticoid for cutaneous disorders. Methods: For the antiproliferative activity assay, a dexamethasone solution and D-NC were tested on Allium cepa root meristem model. D-NC were prepared by the interfacial deposition of preformed polymer. Hydrogels were prepared using Carbopol Ultrez® 10 NF, as polymer, and characterized according to the following characteristics: pH, drug content, spreadability, viscosity, and in vitro drug release. Results and Discussion: Nanocapsules showed mean particle size and zeta potential of 201 ± 6 and ?5.73 ± 0.42 nm, respectively. They demonstrated a lower mitotic index (4.62%) compared to free dexamethasone (8.60%). Semisolid formulations presented acidic pH values and adequate drug content (between 5.4% and 6.1% and 100% and 105%, respectively). The presence of nanocapsules in hydrogels led to a decrease in their spreadability factor. Intact nanoparticles were demonstrated by TEM as well as by dynamic light scattering (mean particle size < 300 nm). In vitro studies showed a controlled dexamethasone release from hydrogels containing the drug associated to the nanocapsules following the Higuchi's squared root model (k = 20.21 ± 2.96 mg/cm²/h^1/2) compared to the hydrogels containing the free drug (k = 26.65 ± 2.09 mg/cm²/h^1/2). Conclusion: Taking all these results together, the hydrogel containing D-NC represent a promising approach to treat antiproliferative-related dermatological disorders.