载表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜的制备及体外释药评价

背景：纤维蛋白胶胶联羊膜作为一种无需缝合生物移植材料还无法有效地在局部长时间缓释药物,特别是对于一些不稳定的生物活性蛋白药物。 目的：构建新型的能有效缓释蛋白药物的载表皮生长因子壳聚糖纳米粒纤维蛋白胶羊膜复合体。 方法：制备表皮生长因子/壳聚糖载药纳米粒并考察其表征,然后将载药纳米粒掺入纤维蛋白胶,再将载纳米粒的纤维蛋白胶和羊膜胶联黏合,制备出负载表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜,并进行形态学和体外释药观察,检测释放出的表皮生长因子生物活性。 结果与结论：表皮生长因子/壳聚糖纳米粒的粒径为(275.7±6.8) nm,Zeta电位为(32.7±0.6) mV,包封率为(67.03±1.22)%,多分散指数为0.23±0.04,形态圆形均一,载纳米粒纤维蛋白胶能够很好地与羊膜胶联黏合,表面呈网状结构,纳米粒充斥其中。载表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜体外释药可达14 d,释放的表皮生长因子生物活性可保持7 d以上。说明制备的载重组人表皮生长因子/壳聚糖纳米粒纤维蛋白胶胶联羊膜作为一种无缝合生物移植材料可在局部缓慢释放表皮生长因子。     

载异烟肼利福平聚乳酸纳米粒的制备及体外释药**

背景：微载体药物因具有靶向性、控释性、稳定性、更好的安全性备受关注。 目的：观察载异烟肼利福平两种抗结核药于同一聚乳酸纳米粒的给药系统及体外释放特性。 方法：采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,亚微粒径分析仪测定纳米粒粒径及分布,透射电镜观察其形态;高效液相色谱仪建立测定异烟肼、利福平的载药量和包封率;以磷酸盐缓冲液为释放介质,观察载异烟肼和利福平纳米粒的体外释药特性。 结果与结论：载利福平和异烟肼纳米粒表面完整光滑,无明显粘连现象,纳米粒均匀度好。亚微粒径分析仪测定纳米粒平均粒径80.4 nm。异烟肼载药量为(15.95±1.34)%,包封率为(5.01±0.17)%;利福平载药量为(4.66±0.97)%,包封率为(4.05±0.18)%。体外释药结果显示纳米粒的体外释药过程较平稳。突释期纳米粒中异烟肼释放度为15.22%,到3 d累积释放度可达95.6%;利福平释放度为9.26%,到3 d累积释放度可达90.3%。提示采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,所得载药纳米粒的粒径小且较均匀。纳米粒体外释药过程较平稳,无明显突释现象。关键词：聚乳酸;异烟肼;利福平;纳米粒;体外释药 doi:10.3969/j.issn.1673-8225.2012.16.014     

姜黄素纳米粒对人视网膜色素上皮细胞增殖的影响

背景:姜黄素具有抑制人视网膜色素上皮细胞增殖及抗新生血管的作用,在防治眼底新生血管性病变中可以发挥重要作用,但其水溶性较差、体内半衰期短,需要长期、多次注射用药,因此研制姜黄素的新剂型具有重要临床意义。目的:探讨脱氧胆酸基接枝的壳聚糖衍生物负载姜黄素纳米粒的合成方法,以及其对人视网膜色素上皮细胞增殖的影响。方法:首先制备壳聚糖-脱氧胆酸纳米粒,随后制备姜黄素/壳聚糖-脱氧胆酸纳米粒,检测姜黄素/壳聚糖-脱氧胆酸纳米粒的载药量、负载效率及体外释药性能。将人视网膜色素上皮细胞分别与姜黄素(5,10,20,40 mg/L)、壳聚糖-脱氧胆酸纳米粒(5,10,20,40 mg/L)、姜黄素/壳聚糖-脱氧胆酸纳米粒(5,10,20,40 mg/L)共培养,采用CCK-8法检测细胞增殖。结果与结论:(1)姜黄素/壳聚糖-脱氧胆酸纳米粒的载药量、负载效率分别为27.5%,55%,体外前10 h内,该纳米粒存在药物突释现象,此后缓慢释放,至96 h后达到平衡,累积释放药物量为31.6%;(2)培养24,48 h,不同质量浓度的壳聚糖-脱氧胆酸纳米粒对人视网膜色素上皮细胞的增殖无明显影响;(3)不同质量...     

乳酸-羟基乙酸共聚物载药纳米粒的制备及体外释药性

背景：医用纳米粒作为药物传递的新型载体,目前已经成为医药领域研究的重点。 目的：构建以生物可降解材料乳酸-羟基乙酸共聚物为载体,负载抗肿瘤药物5-氟尿嘧啶的载药纳米粒。 方法：利用复乳-溶剂挥发法制备乳酸-羟基乙酸共聚物载药纳米粒。场发射扫描电子显微镜观察纳米粒表面形态;激光粒度分析仪测定粒径分布并计算成球率;紫外分光光度计测定5-氟尿嘧啶载药量、包封率,并对体外释药进行评估。 结果与结论：纳米粒呈球性,平均粒径为(186±14) nm,成球率、载药量和包封率分别为70.8%、6.6%、28.1%,体外释药有突释现象,24 h内5-氟尿嘧啶累积释药量达36.2%,10 d达83.6%。提示成功制备乳酸-羟基乙酸共聚物载药纳米粒,其具有缓释效应。     

载表柔比星的壳聚糖纳米粒的制备及其特性研究

目的 制备经聚乙二醇修饰的壳聚糖纳米粒(PEG/CS NP),并负载表柔比星(EPI),研究载表柔比星的壳聚糖纳米粒(PEG/CS-EPI NP)体外释药性能.方法 应用阴离子凝聚法制备PEG/CS-EPI NP,透射电镜观察纳米粒的形态特征,激光粒度分析仪测定粒径大小,紫外分光光度法测定纳米粒的载EPI量,动态透析法考察载EPI纳米粒的体外释放特性.结果 当壳聚糖与三聚磷酸钠质量比为6∶1,壳聚糖与EPI质量比为8∶1时,制备的PEG/CS-EPI NP呈圆形或椭圆形,分散性良好,平均粒径(322.1±14.4)nm,载EPI量为(13.9±1.1)%,包封率(74.2±1.8)%,72 h累积释药率达(82.0±2.1)%.结论 采用阴离子凝聚法制备的PEG/CS-EPI NP形状规则、粒度分布均匀,具有较高包封率和较好缓释性能.     

载基因壳聚糖纳米粒的研究

RNA干扰技术已被广泛应用于心血管领域,壳聚糖纳米粒以其良好的生物特性而作为基因递送载体成为现在研究的热点.就BNA干扰技术与纳米技术在心血管领域的应用及目前常采用的制备壳聚糖纳米粒的方法、影响质粒与壳聚糖纳米粒结合效率的因素、质粒壳聚糖复合物纳米粒转染的影响因素及体外释药行为作一简单的回顾.     

磁性聚乳酸-羟基乙酸氧化苦参碱纳米粒的制备及其特性

目的研究磁性聚乳酸-羟基乙酸氧化苦参碱纳米粒(M-PLGA-OM-NP)的制备工艺,并对纳米粒子进行评价。方法运用复乳法制备M-PLGA-OM-NP,通过透射电子显微镜观察纳米粒形态,并对纳米粒的平均粒径、载药量、包封率、体外释药情况等进行评价。结果纳米粒外观呈规则球形,其平均粒径为146.5 nm,载药量为7.61%,包封率为44.8%。突释后至第72小时,纳米粒维持较稳定的释药速度,累积释放达52.9%。72～240 h,药物释放缓慢,累计释放约为16.6%,体外释放符合Ritger peppas方程lny=1.280 6+lnt。氧化苦参碱药性不受温度影响。结论获得了较满意的M-PLGA-OM-NP制备工艺,其过程简单,粒子性状符合要求。     

两亲性壳聚糖衍生物负载及缓释醋酸曲安奈德的性能

背景:醋酸曲安奈德是一种长效肾上腺糖皮质激素,具有较强的抗炎作用。近年来在眼内疾病的治疗中取得了较好的效果,但同时带来一些不良反应,且需多次注射,以防止疾病复发。壳聚糖经接枝改性,生成的共聚物可在水溶液中生成纳米粒,用于药物的缓释载体,延长药物作用时间,降低不良反应,提高生物利用度。目的:合成含脱氧胆酸基团的两亲性壳聚糖衍生物作为醋酸曲安奈德的载体材料,制备具有缓释功能的载药纳米胶束,研究其负载和缓释醋酸曲安奈德的性能。方法:通过酰胺化反应在壳聚糖上偶联脱氧胆酸基团,合成两亲性壳聚糖衍生物。透射电镜观察纳米粒的外观形态和粒径,Zeta电位分析仪测定纳米粒的Zeta电位,体外释放实验检测负载醋酸曲安奈德的壳聚糖-脱氧胆酸纳米粒的包封率、载药量和体外释药性能。结果与结论:合成出含脱氧胆酸基团的两亲性壳聚糖衍生物,它能与醋酸曲安奈德形成载药纳米胶束,载药量可高达82%。随着载药量的增加,载药纳米胶束的粒径逐渐增大,而Zeta电位则呈下降的趋势。体外释放的结果表明载药纳米胶束能起到72h缓释醋酸曲安奈德的作用。提示以两亲性壳聚糖衍生物为载体的载药纳米胶束显示出较好的缓释醋酸曲安奈德性能,将有希望提高醋酸曲安奈德的治疗效果。     

表柔比星壳聚糖隐形纳米粒的制备及其抗肿瘤活性的检测

目的 制备包裹抗癌药物表柔比星（EPI）的"隐形"壳聚糖纳米粒,并检测其抗肿瘤活性。方法 应用阴离子凝聚法制备负载EPI的PEG化壳聚糖纳米粒（PEG/CS-EPI NPs）和普通壳聚糖纳米粒(CS-EPI NPs),通过透射电镜和动态光散射方法表征粒子的形貌和尺寸分布,用MTT法测定鼻咽癌细胞的增殖抑制率;并通过尾静脉注射给药法对荷小鼠肉瘤细胞S-180小鼠进行体内抑瘤试验。结果 PEG/CS-EPI NPs呈圆形或椭圆形,平均粒径322nm,载药量为13%,包封率74%,抑制细胞增殖具有浓度和时间依赖性,与普通壳聚糖纳米粒相比,隐形纳米粒的体内抗肿瘤作用更明显。结论 隐形壳聚糖纳米粒较普通壳聚糖纳米粒更适合用于制备化疗药物载体。     

骨髓炎治疗用缓释制剂的制备及体外抑菌活性研究

骨髓炎的定点缓释给药治疗是重要的生物医学问题,关键是要制备高效的缓释药棒。我们采用热熔法,以聚(二聚酸(十四烷二酸)共聚物[P(DA-TA),WDA:WTA=50:50]为药物缓释材料,硫酸庆大霉素为模型药物,制备了硫酸庆大霉素-聚酸酐缓释药棒,以期最终用于骨髓炎的定点缓释给药治疗。初步的制剂稳定性研究表明,在室温干燥条件下,该缓释药棒具有良好的制剂稳定性。体外释药结果表明,37℃时,该缓释药棒在蒸馏水中、0．9％生理盐水中和0．1 mol／L pH7．4 PBS中具有明显缓释作用,其体外释药动力学均符合一级动力学方程和Peppas方程。抑菌活性实验表明,该缓释药棒对骨髓炎常见致病菌:金黄色葡萄球菌及大肠杆菌有长达60 d的抑制作用。该类硫酸庆大霉素-聚酸酐缓释药棒具有良好的制剂稳定性和长达60 d的抑菌活性,可望用于骨髓炎治疗领域。     

Electrospraying: a facile technique for synthesis of chitosan-based micro/nanospheres for drug delivery applications

Electrospraying is a novel technique for the generation of micro/nanospheres for biomedical applications. Apart from being a high yield technique; electrospraying has an added advantage of not making use of an external dispersion/emulsion phase which often involves ingredients that are undesirable for biomedical applications. In this study, we report the use of electrospraying for the synthesis of chitosan micro/nanospheres. The focus was to optimize the fabrication parameters involved in electrospraying for reproducible synthesis of chitosan based micro/nanospheres and to study their potential as delivery vehicles for bioactive agents. The influence of the following was studied (i) electrospraying voltage, (ii) needle gauge, (iii) concentration of chitosan solution, (iv) concentration of acetic acid solution, and (v) electrospraying distance. SEM analysis demonstrated that microspheres of less than 1 mum were obtained when chitosan concentration was 2% dissolved in 90% acetic acid. The working distance and needle gauge that yielded favorable results were 7 cm and 26 g, respectively. Average particle size of ampicillin loaded chitosan micro/nanospheres was 520 nm with zeta potential of +28.2 mV and encapsulation efficiency of 80.4%. The particles were characterized for drug release kinetics and results demonstrated an initial burst release followed by a sustained release over a period of 120 h. Further, antibacterial activity of drug loaded micro/nanospheres demonstrated that the encapsulated drug was in its active form postexposure to high voltage during electrospraying. This study indicates that electrospraying is a facile technique for the synthesis of chitosan micro/nanospheres for drug delivery applications.     

Paclitaxel-loaded silk fibroin nanospheres

Silk fibroin is a very promising biomedical material because of its renewability, nontoxicity, biocompatibility, and biodegradability. On the basis of a simple and mild method for the preparation of silk fibroin nanospheres with controllable size, the authors developed earlier, anti-cancer drug paclitaxel (PTX)-loaded silk fibroin nanospheres ranging from 270 to 520 nm were produced accordingly. The drug loading, encapsulation efficiency, and released property of PTX-loaded silk fibroin nanospheres are depended on the silk fibroin concentration and initial PTX-loading capacity. The maximum drug loading is about 6.9% and the release time of such a kind of nanospheres is over 9 days. The release time of PTX-loaded silk fibroin nanospheres can be as long as 2 weeks when the drug loading is about 3.0%. All these results imply that such a kind of biomacromolecule-based anti-cancer drug nanocarrier has a great potential for chemotherapy in clinical applications.     

纳米尿激酶的性状研究

背景：尿激酶半衰期短,需持续大量给药,并发症也不小,故有必要研制具有缓释作用的溶栓药物。 目的：了解包载尿激酶的水溶性壳聚糖纳米粒子的性状。 方法：将壳聚糖和三聚磷酸钠以离子凝集法制备尿激酶纳米粒子后,用透射电镜观察其形态,采用粒径仪测纳米粒子粒径,酶标仪比色法测粒子包封率,纳米粒子冻干法测其载药量,并检测体内外纳米粒子缓释特性。 结果与结论：当壳聚糖、三聚磷酸钠、尿激酶的质量比为7∶1∶1时,不仅溶液稳定,形成的纳米粒子粒径小,而且包封率和载药量均合适。制备出包封率最高达94.8%的尿激酶纳米粒子,载药量为14.5%,此时平均粒径236 nm,透射电镜观察示粒子形态较规则,呈球形;粒子具有较好的缓释性能;表明将尿激酶包被于纳米粒子中,避免了消化酶的直接作用,延长了半衰期,不仅在体内能保持较长时间的活性,而且具有明显的缓释效果。     

Protein release kinetics for core-shell hybrid nanoparticles based on the layer-by-layer assembly of alginate and chitosan on liposomes

The present work is focused on the formulation of core-shell nanoparticles via the layer-by-layer (L-b-L) self-assembly technique for delivery of biomacromolecules such as bone growth factors. The drug encapsulation efficiency of liposomes is enhanced with the increased stability of polyelectrolyte systems achieved through the alternate adsorption of several layers of natural polymers: anionic alginate and cationic chitosan on cationic nanosized phospholipid vesicles. The resulting particles were characterized for their size, surface charge, morphology, encapsulation efficiency, loading capacity and release kinetics over an extended period of 30 days. The L-b-L deposition technique succeeded in building a spherical, monodisperse and stable hybrid nanoparticulate protein delivery system with a cumulative size of 383+/-11.5 nm and zeta potential surface charge of 44.61+/-3.31 mV for five bilayered liposomes. The system offers numerous compartments for encapsulation including the aqueous core and within the polyelectrolyte shell demonstrating good entrapment and sustained linear release of a model protein, bovine serum albumin, in vitro. Our results demonstrate that this delivery system features an extended shelf life and can be loaded immediately prior to administration, thus preventing any loss of the protein.     

全反式维甲酸-聚酸酐长效缓释剂研制及其可行性

背景：如何提高全反式维甲酸疗效、稳定性和降低毒副作用是临床治疗所面临的最大问题。近年来用可生物降解的聚合物为材料,通过乳化包囊等分散技术将药物制备成微粒分散体系,用作缓释、控释注射剂的研究日益增多。 目的：研制全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,观察其体内外全反式维甲酸经时缓释变化规律。 方法：采用乳剂-扩散溶剂挥发法制备全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,扫描电镜检测微球外观及微球粒径,高效液相色谱法检测微球载药量、包封率及体内外释药量。 结果与结论：所制微球治疗剂光滑圆整,大小均一,平均粒径(154.42±26.76) nm,载药率(16.5±1.45)%,包封率(87.84±4.79)%;体外释放实验证明该微球治疗剂可持续释放全反式维甲酸约50 d,将其肌肉注射到大耳白兔体内,可稳定缓释全反式维甲酸近45 d。结果表明该微球治疗剂载药量及包封率均较高,体内外释药平稳并且具有明显的长效缓释作用。     

9-硝基喜树碱叶酸聚合物胶束肿瘤靶向给药系统的表征及体外药效评价

背景：近年来,两亲性聚合物胶束作为难溶性药物载体和叶酸介导的肿瘤细胞靶向给药系统在药剂学研究领域受到极大的关注。 目的：制备包载9-硝基喜树碱的叶酸聚合物胶束并进行理化表征及体外药效评价。 方法：采用薄膜-水化法制得载药胶束,利用激光粒度分析仪检测胶束粒径大小,反相高效液相层析法检测载药量,透析法进行体外释放试验;利用肿瘤细胞摄取及体外生长抑制试验,对叶酸聚合物胶束作体外药效评价。 结果与结论：制得的9-硝基喜树碱叶酸聚合物胶束粒径为24~26 nm,载药量为3.24%,24 h累积释放百分率约90%。叶酸修饰的聚合物胶束对肿瘤细胞的亲和性及抗肿瘤活性显著高于普通胶束。提示叶酸修饰的聚合物胶束可为难溶性药物提供一种具有良好应用前景的肿瘤主动靶向纳米载药系统。     

5-氟尿嘧啶缓释剂制备及体外释药性能比较*

背景：5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释微球在青光眼滤过术后抑制滤过泡的瘢痕化具有潜在应用价值,但微球制备程序复杂,微球载药量一般较低,且药物突释现象明显。 目的：比较乳化溶剂挥发法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球和喷雾成膜法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜两种缓释剂的形态、载药量、体外释放规律,以探讨获得缓释效果较佳的5-氟尿嘧啶缓释剂制备方法。 方法：以聚乳酸-乙醇酸共聚物为载体,采用乳化溶剂挥发法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球;用喷雾成膜法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜。 结果与结论：用乳化溶剂挥发法制备的微球外观圆整,粒径为(4 447.4±359.8) nm,载药量(8.67±0.37)%,包封率为(86.68± 1.92)%;用喷雾成膜法制备的缓释膜表面光滑平整,质量为(13.76±0.26) mg ,直径为6 mm ,厚度为(0.24±0.005) mm,载药量(23.76±0.37)%,包封率为(95.04±1.36)%。缓释剂制备过程未影响5-氟尿嘧啶的药物性能。微球体外释放突释明显,缓释膜的体外释放平稳持久,释放曲线符合Higuchi方程。结果表明缓释膜制备方法更简单易行,且能明显提高缓释剂的载药量,降低突释现象,同时延长药物的缓释时间。 关键词：聚乳酸-聚乙醇酸;5-氟尿嘧啶;微球;缓释膜;体外释放 doi:10.3969/j.issn.1673-8225.2012.08.022     

Poly(methyl methacrylate)-grafted chitosan microspheres for controlled release of ampicillin

Microspheres of 50-500 microm diameter were prepared from a blend of chitosan and chitosan-g-PMMA. Environmental scanning electron microscopic and SEM studies revealed that the microspheres are porous and the pores extend toward the inner core of the microspheres. The microspheres were also found to be hemocompatible and cytocompatible. A model drug ampicillin was used to evaluate the drug loading capacity and the controlled release properties of the microspheres. The system maintained a sustained release of ampicillin for a period of more than 8 days. The drug-loaded chitosan/chitosan-g-PMMA microspheres exhibited higher antibacterial activity for both the gram positive (ATCC 25923 S. aureus) and gram negative (ATCC 25922 E. coli) bacteria than the drug-loaded virgin chitosan microspheres. The percentage release and bioactivity of ampicillin was found to be higher for the chitosan/chitosan-g-PMMA microspheres than the virgin chitosan microspheres. Potential applications such as oral drug delivery, wound dressings, tissue engineering, and so forth, are envisaged from these microspheres.