二甲双胍丝素微球的制备工艺研究

目的以丝素蛋白为载体,二甲双胍为模型药物,制备二甲双胍丝素微球,优选最佳制备工艺。方法以液状石蜡为油相,再生丝素溶液为水相,Span 80为乳化剂,采用乳化固化法制得二甲双胍丝素微球,应用激光粒径分布仪测定微球的粒径及其分布,单因素考察影响微球载药量和包封率的因素,并进一步采用正交实验优选微球的最佳制备工艺。结果所制得的微球圆整,微球的粒径分布在4～40μm之间。对微球载药量和包封率影响较大的因素为投药比、水油比和转速,最佳工艺条件是:投药比为7%、转速为300 rpm、水油比为11∶100,载药量可达5.8%。结论该二甲双胍丝素微球制备方法简单,无有毒有害物质加入,可在常温常压下制备,易于扩大生产。     

乙基纤维素载药纳米粒的制备与体外性能研究

目的 用乙基纤维素制备环丙沙星纳米粒,并对其进行体外释放性能的测定。方法 以环丙沙星为主药,乙基纤维素为主要辅料,采用液中干燥法制备环丙沙星纳米粒,并用透析法进行体外释放度的测定。结果 纳米粒平均粒径为690 nm,载药量（33.90±0.54）%,包封率（90.40±0.48）%,在105 h后药物体外释放达到86.38%。结论 采用乙基纤维素制备的环丙沙星纳米粒具有明显的缓释效果.     

利福平明胶微球剂制备工艺的研究及包封率检测

本文研究了制备利福平明胶微球影响粒径的因素,通过正交实验得出了制备该微球剂的最佳工艺条件;本文阐述了用生物降解的弓法破坏利福平微球,使之释放主药,从而检测包封率的方法。本文方法制得的利福平明胶微球粒径为10.58±2μm,包封率为85.12％,微球在室温及37℃以下性质稳定。     

槲皮素纳米混悬剂的制备及其性能研究

目的制备高载药量、小粒径的槲皮素纳米混悬剂,并进行性质考察。方法采用纳米沉淀–高压均质法制备,以粒径分布、药载比、稳定性为指标对处方和工艺进行优化,并对最优处方进行体外性质考察。结果以超声注入联合高压均质法制备,最佳处方为TPGS为稳定剂、DMF为有机试剂,药载比为5∶1;最佳工艺条件为低温10℃超声、200 MPa、循环5次。制备得到的槲皮素纳米混悬剂粒径为(173.21±0.90)nm,电位为(-19.02±0.15)m V,载药量为(80.40±1.44)%,包封率为(96.41±1.72)%。药物在纳米粒中以结晶状态存在,能够体外缓释36 h。结论利用TPGS可制备高载药量、小粒径的槲皮素纳米混悬剂,其体外具有明显缓释作用,解决了槲皮素水溶性差的难题,具有较好的应用前景。     

HPLC法测定醋酸曲普瑞林微球的载药量及包封率

目的 建立HPLC法测定醋酸曲普瑞林微球的载药量和包封率的方法.方法 色谱柱为Phenomenex Kinetex? EVO C18(150 mm×4.6mm,5 μm);流动相为0.05 mol·L-1磷酸溶液(用三乙胺调节pH值至3.5)-乙腈(78 ∶22);柱温35℃;流速为1.0 mL·min-1;检测波长为...     

去甲斑蝥素壳聚糖-丝素蛋白栓塞微球的制备以及体外释放研究

目的:研究利用壳聚糖(chitosan,CS)和良好生物相容性的丝素蛋白(silk fibroin,SF)为载体,去甲斑蝥素(norcantharidin,NCTD)为模型药物,制备去甲斑蝥素壳聚糖-丝素蛋白微球(norcantharidin-chitosan-silk fibroin-microspheres,NCTD-CS-SF-MS)。并考察微球的载药量、包封率及微球表面形态以及微球的体外释放特性。方法:以液体石蜡为油相,壳聚糖与丝素蛋白的物理混合溶液为水相,Span-80为乳化剂,戊二醛为交联剂;采用乳化-交联固化法制备NCTD-CS-SF-MS。星点设计优化制备工艺,扫描电镜,观察微球表面形态及X-射线粉末衍射法(X-ray power diffraction,X-RD)和差示扫描量热法(differential scanning calorimetry,DSC)表征微球特性;采用体外动态透析法测定微球在不同介质条件下的释药性能。结果:制备的NCTD-CS-SF-MS形态圆整,粒径分布较为均匀,平均粒径约(184.0±5.0)μm,载药量(15.08±2.85)%,包封率(27.46±1.25)%。NCTD-CS-SF-MS在0.1mol/L HCl,PBS(pH=7.4)和9.0mg/mL氯化钠溶液的3种介质中的释放均遵循Weibull方程。结论:优化的NCTD-CS-SF-MS制备工艺简单易行,载药量高,缓释作用良好。     

喷雾干燥环丙沙星白蛋白微球的载药量和包封产率

建立和采用一阶导数紫外分光光度法测定白蛋白微球中环丙沙星的含量,该法可避开白蛋白囊材对微球中环丙沙星含量测定的干扰,操作简便,结果准确可靠。测得1：1、1：2和1：4等不同药物／囊材比例的喷雾干燥微球中环丙沙星的载药量分别为46．93％、32．65％、20．56％,讨论并分析微球制剂中药物的分析方法,以恰当的包封产率评价方法计算喷雾干燥工艺对环丙沙星进行微囊化的包封产率的影响,结果满意。     

鞣花酸壳聚糖-海藻酸钠微球的制备工艺

目的:优化鞣花酸壳聚糖-海藻酸钠微球的最佳制备工艺。方法:采用一步法,以壳聚糖-海藻酸钠作为载体材料制备鞣花酸微球,并以微球载药量和包封率为考察指标,通过单因素筛选及正交设计优化出鞣花酸壳聚糖-海藻酸钠微球的制备工艺。用溶出仪在900 ml释放介质(pH 6.86)和120 r·min^-1转速条件下测定释放度。结果:优化工艺为海藻酸钠与药物比为3:1,氯化钙质量分数为2%,海藻酸钠质量分数为2%,壳聚糖质量分数为0.1%,温度为60℃,pH为5,所得鞣花酸平均粒径为(980±100)μm,平均载药量为27.22%,平均包封率为97.73%,48 h释放度为74.22%。结论:本制备工艺稳定,操作简便,重现性好,可用于鞣花酸壳聚糖-海藻酸钠微球的制备。     

聚乳酸-羟基乙酸共聚物载药微球性质及缓释行为的影响因素

聚乳酸-羟基乙酸共聚物（PLGA）包裹药物制成缓释微球是药物缓释方向的研究热点,PLGA微球作为载体,具有良好的生物相容性和降解性,但载药微球的性质和释药性能易受很多因素影响,如PLGA相对分子质量,LA/GA比例,微球制备工艺等,这些因素对载药体系在生物医学领域的应用造成一定限制。结合国内外相关文献,本文综述了PLGA微球在制备及释药过程中,影响其理化性质和重要性能的因素,包括载药量,包封率,突释问题等方面,为PLGA微球进一步研究和优化提供思路。     

PLGA微球的制备及其用于脉冲给药的初步研究

目的：制备聚乳酸-羟基乙酸共聚物（PLGA）微球,并考察其用于脉冲式释药系统的可行性。方法：以牛血清白蛋白（BSA）为模型药物,用S/O/W（Solid-in-oil-in-water）法和S/O/O（Solid-in-oil-in-oil）法制备PLGA（75：25）和PLGA（50：50）微球,比较2种方法制备的微球的表面形态、包封率及载药量等,并考察2种微球的体外释放行为。结果：S/O/W法和S/O/O法制备的微球均圆整、无粘连、形态良好,但S/O/W法制备的微球表面较为平整,而S/O/O法表面均匀分布有较大的凹陷。S/O/W法制备的PLGA（75：25）和PLGA（50：50）微球包封率分别为（60.15±5.95）%、（49.50±3.69）%,载药量分别为（2.56±0.25）%、（2.10±0.16）%,10h内药物释放均为10%左右,而后随着聚合物的降解药物的释放量突然增加;S/O/O法所制微球包封率分别为（84.36±1.11）%、（77.94±1.42）%,载药量分别为（3.58±0.05）%、（3.31±0.06）%,24h内药物释放均可达50%左右,而后呈现较为平稳的释放行为。S/O/O法制备的微球包封率及载药量均较S/O/W法高;S/O/W法制备的PLGA微球药物释放呈现一定的脉冲行为,其中PLGA（75：25）微球体外释放行为受微球粒径的影响较大。结论：S/O/W法制备的PLGA微球具有一定的脉冲式释药效果,微球的粒径最好控制在120μm以下。     

棉酚白蛋白纳米粒的制备及其体外释放

目的:优化超声-溶剂沉淀法制备棉酚白蛋白纳米粒的工艺。方法:采用正交设计,以白蛋白浓度、有机相与水相比、乳化分散时间为考察因素,根据L9(34)正交设计原理安排实验,对包封率、载药量、平均粒径进行归一化处理后,再以总体的归一值为综合评价指标,优化出处方。对优化出的制剂采用透射电镜进行观察,并且进行体外释放研究拟合药物释放曲线。结果:优化的最佳条件为白蛋白浓度1%,有机相与水相比2∶25,高剪切乳化时间60 s,在此条件下制备的棉酚白蛋白纳米粒载药量为15.34%,包封率为91.21%,粒径为435 nm。结论:制备的白蛋白纳米粒体外有缓释能力,拟合方程符合Higuchi方程。     

Intracellular macrophage uptake of rifampicin loaded mannosylated dendrimers

The present study was aimed at developing and exploring the use of mannosylated dendritic architecture for the selective delivery of an anti-tuberculosis drug, rifampicin (RIF) to alveolar macrophages (AM). The mannosylated dendritic architecture was synthesized and characterized by using IR and NMR spectroscopy. RIF was efficiently loaded into mannosylated dendrimer using dissolution method. Various physicochemical and physiological parameters such as UV, SEM, DSC, drug loading, solubilization, pH dependent in-vitro release, hemolytic toxicity, phagocytic AM uptake and cytotoxicity concerning the mannosylated dendrimer were evaluated. RIF loaded mannosylated dendrimer reduced release rate of drug in pH 7.4, hemolytic toxicity and cytotoxicity; whereas enhanced drug release in pH 5.0 and AM uptake was observed. The present novel dendritic system displayed suitability in terms of biocompatibility and site-specific delivery of antitubercular drug RIF.     

负载胰岛素壳聚糖接枝醋酸乙烯酯纳米粒的制备和性能

目的:制备负载胰岛素壳聚糖-醋酸乙烯酯共聚物纳米粒并研究其性能。方法:用自由基聚合法合成壳聚糖-醋酸乙烯酯共聚物,该聚合物在水中形成具有疏水核心、亲水表面的纳米粒。采用正交设计试验研究了投料比、引发剂浓度和反应时间对纳米粒粒径的影响。结果:对纳米粒进行了热重分析和红外表征。测定纳米粒的形态、粒径和表面电位(Zeta电位),以胰岛素为模型药物,研究纳米粒的包封和释药性能。结论:纳米粒呈球形,粒径均匀,表面荷正电。胰岛素的包封率可达90%以上。pH6.8的磷酸盐缓冲液中胰岛素释放较慢。结论:该纳米制剂具有较好的物理性能和体外缓释特性。     

Preparation,characterization, and in vitro evaluation of isoniazid and rifampicin‐loaded archaeosomes

The ability of Archaea to adapt their membrane lipid compositions to extreme environments has brought in archaeosomes into consideration for the development of drug delivery systems overcoming the physical, biological blockades that the body exhibits against drug therapies. In this study, we prepared unilamellar archaeosomes, from the polar lipid fraction extracted from Haloarcula 2TK2 strain, and explored its potential as a drug delivery vehicle. Rifampicin and isoniazid which are conventional drugs in tuberculosis medication were loaded separately and together in the same archaeosome formulation for the benefits of the combined therapy. Particle size and zeta potential of archaeosomes were measured by photon correlation spectroscopy, and the morphology was assessed by with an atomic force microscope. Encapsulation efficiency and loading capacities of the drugs were determined, and in vitro drug releases were monitored spectrophotometrically. Our study demonstrates that rifampicin and isoniazid could be successfully loaded separately and together in archaeosomes with reasonable drug‐loading and desired vesicle‐specific characters. Both of the drugs had greater affinity for archaeosomes than a conventional liposome formulation. The results imply that archaeosomes prepared from extremely halophilic archaeon were compatible with the liposomes for the development of stable and sustained release of antituberculosis drugs.     

Preparation and in vitro release of zein microparticles loaded with prednisolone for oral delivery

Zein has been proposed as a polymer for targeted-drug delivery via the oral route. Zein microparticles were loaded with prednisolone and evaluated as an oral delivery system. Microparticles were formulated using phase separation. Starting quantities of zein and prednisolone, along with the agitation method and temperature were found to significantly impact drug loading and loading efficiency. Vortex mixing produced the highest drug loading and loading efficiency. Drug release was measured in simulated conditions of the stomach and small intestine using the microparticles made with the method that best improved drug loading. In simulated stomach and small intestine conditions, prednisolone release reached almost 70% over 3 and 4?h, respectively. While a clinically relevant dose may be delivered using c. 100?mg of zein microparticles, prednisolone release from the microparticles indicates that they may not be suited as a controlled- or targeted-delivery system.     

格列吡嗪壳聚糖-三聚磷酸钠pH敏感性微球的制备及性能研究

目的:以壳聚糖为载体,制备格列吡嗪壳聚糖-三聚磷酸钠pH敏感性微球,并对其性能进行研究。方法:采用正交试验设计法L9(34)优化处方组成及微球制备工艺,通过扫描电镜法、红外光谱法对微球的表面形态及内部结构进行表征,并对其体外释放性能进行研究。结果:最佳工艺条件下制得的微球形状圆整、表面光滑,平均包封率、载药量、粒径分别为75.17%,11.04%和50μm。此微球在模拟胃液中3 h,累积释放率达50%,转移到肠液中19 h后,累积释放率达80%。结论:该微球具有明显的pH敏感性和控释性能。     

载尿激酶脂质微泡制剂的制备及其理化性质检测

<正>随着超声造影剂的不断发展,超声造影剂在疾病的诊断方面发挥了巨大作用并且在疾病治疗方面也已成为国内外的研究热点。以脂质微泡为载体,将特定的药物、基因与脂质微泡相连接,与超声联用可达到药物在目标组织的富集,从而更好的发挥药物的治疗作用,并减少药物在全身的不良反应。国内外研究已有报道超声可增强溶栓药物的作用[1-3],若能将溶栓药物与微泡相结合将更有助于局部溶栓     

Preparation of sustained release rifampicin microparticles for inhalation

Objectives The aim of this research was to develop a novel carrier‐free dry powder formulation of rifampicin for inhalation with controlled‐release properties. Methods Rifampicin dihydrate (RFDH) microcrystals were prepared by a polymorphic transformation of rifampicin. The prepared RFDH microcrystals were coated with poly (dl ‐lactide‐co‐glycolide) or poly (dl ‐lactide), using a spray‐dryer equipped with two different types of three‐fluid (3F) spray nozzles. The physicochemical and aerodynamic properties of the coated RFDH microcrystals were compared with those of conventional matrix microparticles. Key findings The coated RFDH powder, encapsulating 50% of rifampicin, was successfully prepared by simple in‐situ coating methods using two different types of 3F nozzles and had mass median aerodynamic diameter values of 3.5–4.5 µm . The thin flaky morphology of RFDH powders, providing good aerosolization properties, was maintained after coating. The coated RFDH formulations showed relatively low initial rifampicin release, compared with the uncoated RFDH crystals, followed by slow rifampicin release (about 70%) over 8 h in phosphate‐buffered saline media (pH 7.4). Significant chemical degradations were not observed from the crystalline‐structured RFDH formulations, while the amorphous‐structured matrix formulations showed chemical degradation in six months. Conclusions These polymer coated RFDH formulations may be a valuable alternative in the treatment of tuberculosis since the carrier‐free formulation offers the benefit of delivering a maximum‐potency formulation of the antibiotic directly to the site of infection, and long drug residence times may be achieved by the controlled release of the drug.