伊曲康唑固体脂质纳米粒的体外释放研究

目的：研究伊曲康唑固体脂质纳米粒（ITN）的体外释药行为。方法：采用动态透析法。分别精密吸取ITN混悬液和同浓度的伊曲康唑溶液于预处理过的透析袋中,于（37±1）℃恒温摇床中进行体外释放试验,释放介质为1%吐温80-0.7%浓盐酸（10：7）溶液;采用高效液相色谱法测定伊曲康唑含量;以不同时间取样的累积释药率数据进行不同释药模型的拟合。结果：6h时伊曲康唑溶液几乎释放完全,累积释放率已达到96.32%,释药行为符合一级动力学方程;而ITN仅释放37.93%,其释药行为符合Weibull方程。结论：ITN在体外具有良好的缓释作用。     

伊曲康唑固体脂质纳米粒的制备

目的:制备伊曲康唑固体脂质纳米粒,并考察其理化性质.方法:采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN);在脂质、表面活性剂等辅料和主药用量的单因素考察基础上,以包封率为评价指标,采用正交试验设计,优化处方组成和制备工艺;用低温超速离心法测定包封率,透射电镜观察形态,激光粒径分析仪测定粒径和ξ电位.结果:脂质、表面活性剂和主药的用量对ITZ-SLN包封率均有不同程度的影响.以优化处方制备的伊曲康唑固体脂质纳米粒为类球形实体,粒径分布比较均匀,平均粒径为dav=(118.2±15.00)nm,ξ电位(-37.06±0.53)mV,包封率(92.11±1.60)%.结论:乳化-低温固化法制备伊曲康唑固体脂质纳米粒工艺可行.     

伊曲康唑纳米粒的制备及其在小鼠体内的分布

用HPLC法测定了小鼠单剂量(20mg/kg)尾静脉注射伊曲康唑纳米粒及其市售注射剂后心、肝、脾、肺、肾、脑和血浆中的药物浓度.结果表明,伊曲康唑纳米粒在肺中的AUC为注射剂的32.94倍;在心、肾组织的蓄积量减少,在各组织中的半衰期延长,尤以肝、脾、肺为甚.说明伊曲康唑纳米粒的肺靶向性明显优于市售注射剂.     

伏立康唑白蛋白纳米粒大鼠体内药动学与组织分布

摘 要 目的：制备伏立康唑白蛋白纳米粒,并考察其在大鼠体内药动学与及组织分布。 方法: 采用超高压微射流技术制备伏立康唑白蛋白纳米粒,并评价了白蛋白纳米粒的粒径分布、Zeta电位、外观形态以及体外释药行为;考察了伏立康唑白蛋白纳米粒在大鼠体内的药动学与组织分布特征。 结果: 本研究制备的伏立康唑白蛋白纳米粒平均粒径为（121.9±41.6）nm,PdI为0.197,Zeta电位为（-42.1±0.9）mV,呈球形或类球形分布;伏立康唑白蛋白纳米粒在0.5%吐温80磷酸盐缓冲液（pH 7.4）中24 h累积释放67.5%;大鼠体内药动学研究表明,伏立康唑白蛋白纳米粒和伏立康唑注射剂的AUC0-24分别为（98.27±1.42）和（105.32±1.45）g?h?L^-1,MRT0-24分别为（4.48±0.38）和（4.86±0.51）h;伏立康唑白蛋白纳米粒能增加药物在大鼠肝、脾、脑中的靶向性。 结论:伏立康唑白蛋白纳米粒在大鼠体内具有良好的肝、脾、脑中靶向性,可以提高药物治疗疗效。     

去甲斑蝥素白蛋白纳米粒的制备及质量评价

摘 要 目的：制备去甲斑蝥素白蛋白纳米粒,并考察其理化性质。方法: 采用超高压微射流技术制备去甲斑蝥素白蛋白纳米粒,以白蛋白纳米粒的平均粒径和药物包封率作为评价指标,首先应用Plackett Burman试验设计法筛选出对白蛋白纳米粒性质影响显著的处方和工艺变量,再通过Box Behnken试验设计法对筛选的变量进一步优化。考察了去甲斑蝥素白蛋白纳米粒的外观形态、粒径分布和Zeta电位及体外释药行为。结果:通过优化制备的去甲斑蝥素白蛋白纳米粒呈类球形分布,平均粒径为（105.2±30.1）nm,PdI为0.127,Zeta电位为（-24.7±1.9）mV,在0.5%吐温80磷酸盐缓冲液（pH 7.4）中24 h的累积释放度为81.4%。结论:采用超高压微射流技术制备去甲斑蝥素白蛋白纳米粒,工艺简便可行,重复性好,有望工业化生产。     

姜黄素白蛋白纳米粒的制备与评价

目的:优化姜黄素白蛋白纳米粒的处方工艺并对其特性进行表征。方法:以牛血清白蛋白为载体、通过反溶剂沉淀法制备载姜黄素纳米粒,以粒径为评价指标优选制剂处方及工艺,并考察所得纳米粒的放置稳定性、饱和溶解度及体外溶出度。结果:当有机相和水相体积之比为1∶20、药物与白蛋白用量之比为1∶1.5、保护剂为0.5%(V/V)甘露醇时,所得纳米粒冻干粉平均粒径约为320 nm。其在水、p H 6.8、p H 7.4 PBS中的溶解度显著高于原料药及物理共混物,体外溶出更快,且冻干粉的放置稳定性优于纳米混悬液。结论:白蛋白纳米粒处方能够改善姜黄素的水溶性及溶出度,放置稳定性较佳。     

硫鸟嘌呤白蛋白纳米粒的制备

目的用白蛋白包裹硫鸟嘌呤制成纳米粒,并通过纳米球的形态、载药量、包封率等考察纳米球的质量。方法以白蛋白纳米球为载体材料,硫鸟嘌呤为模型药物,采用乳化一交联固化法制备硫鸟嘌呤白蛋白纳米球。用扫描电镜观察纳米球的形态及其粒径,用紫外分光光度法测定纳米球的载药量和包封率。结果制得硫鸟嘌呤白蛋白纳米球外观呈米黄色,粉末状,球形圆整,粒径分布在189—205nm。载药量为7．31％,包封率为62．40％。结论硫鸟嘌呤白蛋白纳米球具有缓释作用。     

伊曲康唑的不良反应

伊曲康唑 (itraconazole ,斯皮仁诺 )是一种合成的广谱抗真菌药 ,临床上具有疗程短、疗效高、安全性大、依从性好的特点[1 ] 。随着伊曲康唑的广泛应用 ,有关其不良反应报道不断增多。1　水肿患者 ,男 ,因甲癣口服伊曲康唑 0 .2g ,每周 2次 ,服药 5d后出现双下肢水肿 ,水肿蔓延至全身及头面部 ,伴胸闷、气短、无发热 ,实验室检查均正常。立即停药 ,予利尿药及输液 1d后症状减轻 ,4d后症状消失[2 ] 。2　药疹患者 ,女 ,因指、趾甲癣予伊曲康唑间歇冲击疗法治疗。第1疗程服药 7d时 ,面部灼热肿胀瘙痒 ,经服马来那敏后痒止 ,服药 2疗程后面部红…     

伊曲康唑注射液制备研究

介绍了伊曲康唑注射液的制备和质量控制,对制得的伊曲康唑注射液的含量和稳定性等作了研究,结果证明制备方法良好,样品质量可控。     

伊曲康唑脂质体的制备工艺研究

目的:优化伊曲康唑脂质体的制备处方和工艺.方法:采用正交设计法,以伊曲康唑脂质体冻干粉重建包封率、粒径分布、渗漏率3个指标综合评分.结果:伊曲康唑脂质体的最佳工艺处方为药物-脂材比1∶30,胆固醇-磷脂比1∶5.5,去氧胆酸钠-脂材比1∶7,甘露醇和乳糖的用量为处方总重的60%,水合介质为磷酸盐缓冲液(pH=6.0),采用薄膜水化超声-冷冻干燥工艺制备.结论:按最优处方制得的脂质体的外观比较圆整,包封率和粒径均较好.     

伊曲康唑固体分散体制备及体外溶出实验

目的:运用固体分散体技术提高难溶性药物伊曲康唑的溶解度及体外溶出速率.方法:选用聚乙烯吡咯烷酮(PVPK30)为载体,采用喷雾干燥法制备伊曲康唑固体分散体,通过差热分析及X射线衍射对固体分散体进行鉴定,比较考察伊曲康唑及其物理混合物和固体分散体的溶出特性.结果:差热分析、X射线衍射图谱表明药物以无定形状态分散于载体中;体外溶出结果表明固体分散体能显著增加药物在水及人工胃液中的溶出度(45 min时1:4固体分散体体外溶出度为伊曲康唑的11.5倍.1:4固体分散体在0.1 mo1·L-1盐酸中溶解度是伊曲康唑的67倍).结论:伊曲康唑固体分散体能明显提高伊曲康唑的溶解度及体外溶出速率.     

载柚皮素壳聚糖纳米粒的制备及其体外细胞评价

目的：制备柚皮素壳聚糖纳米粒,初步探讨其对人肺腺癌细胞A549的细胞毒性和细胞摄取。方法：以壳聚糖和鱼精蛋白作为载体材料,采用离子胶凝法制备柚皮素壳聚糖纳米粒,透射电镜（TEM）观察其形态,马尔文激光粒度仪测定其粒径、分散度（PDI）和Zeta电位,离心法测定其包封率和载药量,采用恒温振荡水浴法对柚皮素壳聚糖纳米粒进行体外释放度研究,最后采用人肺癌细胞系A549细胞进行了细胞毒性、细胞摄取研究。结果：柚皮素壳聚糖纳米粒为球形或类球形粒子,结构完整,大小均一、球形度好,分散均匀,PDI、粒径、Zeta电位和包封率分别为0.268,139 nm、+15.7 mV和83.34%,柚皮素壳聚糖纳米粒体外释放呈缓释,24 h累积释放量达到了80%以上,体外释药过程用Higuchi方程拟合较好。MTT试验显示不同浓度的壳聚糖纳米粒和细胞作用72 h后,细胞活力均大于95%,本文所制备的壳聚糖纳米粒无细胞毒性。细胞摄取试验表明载FITC的壳聚糖纳米粒和A549细胞作用3 h后,可明显看到大量带绿色荧光的纳米粒穿过细胞膜进入细胞。结论：离子凝胶法成功制得粒径较小的柚皮素壳聚糖纳米粒,具有缓释性好,毒性小,壳聚糖纳米粒摄取率较高,可大大提高药物的利用率,具有广泛的应用前景。     

Preparation and evaluation of inhalable itraconazole chitosan based polymeric micelles

Background

This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA).

Methods

Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and ¹HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering and transmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger.

Results

The polymeric micelles prepared in this study could entrap up to 43.2±2.27 μg of ITRA per milliliter. All micelles showed mean diameter between 120–200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10^-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF) varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process.

Conclusions

In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.     

Preparation of the albumin nanoparticle system loaded with both paclitaxel and sorafenib and its evaluation in vitro and in vivo

Paclitaxel and sorafenib loaded albumin nanoparticles (PTX–SRF-BSA-NPs) were prepared and studied here to avoid the toxicities from the excipients in the Taxol® and explore the effect of such combination on the antitumour efficacy and toxicity. PTX-BSA-NPs and so on were used as controls. The particle size, zeta potential, encapsulation efficiency and morphology were evaluated. Less than 70% of each drug released within 24?h. PTX and SRF existed as molecular or amorphous form in the PTX–SRF-BSA-NPs. The particle size did not change much after 2-month storage in freeze-dried form or 24?h in suspension. The treatment with PTX–SRF-BSA-NPs (7.5?mg?kg^?1 PTX?+?7.5?mg?kg^?1 SRF) exhibited lower myelosuppression than PTX-BSA-NPs (15?mg?kg^?1 PTX) while it remained or increased the antitumour effect in mice tumour models. Compared with the solution containing the same level of PTX and SRF, PTX–SRF-BSA-NPs demonstrated significantly lower haemolysis and myelosuppression effect.     

替尼泊苷磷脂复合物白蛋白纳米粒的制备与表征

目的 制备替尼泊苷磷脂复合物白蛋白纳米粒,并表征其理化性质.方法 以人血清白蛋白和蛋黄卵磷脂E80为辅料,替尼泊苷为主药,采用超声法制备替尼泊苷磷脂复合物白蛋白纳米粒及其冻干制剂.以粒径和多分散系数(PDI)为主要考察指标来优化纳米粒的处方及制备工艺;用激光粒度分析仪和透射电镜对其形态和结构进行表征;用葡聚糖凝胶柱法测定纳米粒的包封率和载药量.结果 成功制备了替尼泊苷磷脂复合物白蛋白纳米粒,平均粒径为182.3 ±11.7 nm,PDI为0.168 ±0.02,Zeta电位为-10.75±1.42 mV,包封率为82.27％±2.74％,载药量为4.29％±0.11％;冻干制剂的外观良好,复溶后的粒径和PDI均符合要求.结论 所用方法简单新颖,具有较好的应用前景.     

Development and in vivo evaluation of chitosan nanoparticles for the oral delivery of albumin

Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein. Several characterizations have been performed for the albumin-loaded nanoparticles (e.g. drug encapsulation efficiency, DSC, FTIR, particle size, zeta potential, morphology, release kinetics, and enzymatic stability). Nanosized spherical particles were prepared and demonstrated high stability over three months either in a powdered form or as suspensions. Sustained release of albumin over time and high enzymatic stability as compared to the free albumin were observed. In vivo, higher serum concentrations of albumin in normal rabbits and cirrhotic rats were attained following oral and intraperitoneal administrations of the albumin-loaded nanoparticles as compared to the free albumin. The nanoparticles developed in the current study might provide efficient nanovehicles for oral administration of therapeutic albumin.     

HPLC法测定人血浆中伊曲康唑的含量及其药代动力学研究

目的建立HPLC法测定人血浆中伊曲康唑含量方法及药代动力学特征的研究。方法选取20名健康受试者高脂饮食后随机交叉口服受试制剂和参比制剂伊曲康唑片100mg。采用HPLC-UV法测定伊曲康唑的血药浓度。结果受试制剂的相对生物利用度为(99.7±9.2)%。结论伊曲康唑的药代动力学特征较明显,表明两制剂具有生物等效性。