重组人血管内皮抑制素壳聚糖纳米粒的制备

目的:通过星点设计-效应面法优化重组人血管内皮抑制素(Endostar)壳聚糖纳米粒的制备工艺。方法:以壳聚糖浓度、三聚磷酸钠(TPP)浓度及壳聚糖溶液与TPP溶液体积比为考察因素,以载药量、包封率和粒径为指标,采用多元线性回归和多元非线性回归拟合选择合适模型,并根据最佳模型绘制效应面图,选择最佳处方,并进行预测分析,同时考察最佳处方的体外释放。结果:用多元非线性回归对实验中各因素和指标进行拟合明显优于线性拟合。最佳处方制备的Endostar载药壳聚糖纳米粒,载药量、包封率及粒径的实测值与预测值的偏差均在±7%以内,体外释放1周累积释放80%。结论:通过星点设计-效应面法可以准确快速优化处方工艺。优化后的工艺制备的纳米粒可以延缓Endostar的释放,达到了缓释效果,符合预期的试验目标。     

雌二醇鼻用壳聚糖纳米粒的制备及体外性质的考察

目的 研究雌二醇壳聚糖纳米粒的理化性质及鼻黏膜吸收动力学.方法 以三聚磷酸钠(TPP)为交联剂,用生物降解聚合物材料壳聚糖(CS)制成纳米粒,通过离子凝胶化法制备雌二醇(E2)壳聚糖纳米粒,分别用动态光散射法仪测定了纳米粒的粒径,高速离心法测定其包封率,透析袋法对其体外释放过程进行了研究,采用大鼠在体灌流模型,考察了质量浓度分别为3.86、7.20、24.75、32.74、51.62 mg·L-1的雌二醇壳聚糖纳米粒的鼻黏膜吸收动力学.结果 当m(CS):m(TPP)在3:1～7:1之间时,可以形成壳聚糖纳米粒,5:1时得到得纳米粒最佳,平均粒径为(279.1±7.2)nm.随着E2质量浓度的增加,包封率有降低的趋势;E2在前2 h内发生突释现象,12 h释放量达80%以上.在循环液体积为5 mL、流速为2.5 mL·min-1下,不同质量浓度的雌二醇壳聚糖纳米粒鼻黏膜吸收速度常数不同,且随药液质量浓度的增加而增大.结论 通过离子凝胶化法制备的壳聚糖纳米粒外观呈半透明状,粒径较为均一,有一定的缓释效果,鼻黏膜吸收具有浓度依赖性,一定质量浓度条件下的吸收动力学过程为符合零级动力学.     

用离子交联-匀化工艺制备乙肝疫苗壳聚糖纳米粒

目的：研究制备乙肝疫苗壳聚糖（chitosan，CS）纳米粒的适宜条件和影响因素。方法：以CS溶液和三聚磷酸钠溶液，采用离子交联-高压匀化工艺制备乙肝疫苗壳聚糖纳米粒，考察CS的浓度、CS与二聚磷酸钠的质量比及高压匀化对壳聚糖纳米粒粒径和多分散系数的影响，测定了载药纳米粒的包封率和载药量。结果：当CS与三聚磷酸钠的浓度都为2mg/mL，质量比为3：1～6：1，通过离子交联-高压匀化工艺可以得到稳定的纳米粒。纳米粒外观圆整，粒径分布均匀，包封率达到90％以上。结论：用离子交联－高压匀化工艺制备CS纳米粒不需要使用有机溶剂，包封率较高，可以满足给药系统应用要求。     

乙酰半胱氨酸纳米粒的制备及体外释放研究

目的制备乙酰半胱氨酸纳米粒,并对其进行体外释放的研究。方法溶剂扩散法制备乙酰半胱氨酸纳米粒,单因素考察了壳聚糖浓度、油相中乙醇浓度、油水相比例对乙酰半胱氨酸纳米粒形态、大小、包封率的影响,通过透析袋法研究乙酰半胱氨酸纳米粒体外释药过程。结果经筛选得到形成纳米粒的最佳工艺为壳聚糖浓度2mg.min-1、乙醇浓度25%、油水相比为10∶1。该工艺制备纳米粒大小圆整,粒径为163±12.8nm,包封率达81%。体外释放结果表明,乙酰半胱氨酸纳米粒具有一定的缓释作用,药物在24h累积释放74.5%。结论溶剂扩散法制备乙酰半胱氨酸纳米粒方法简便、药物包封率高,该纳米粒是一种比较理想的乙酰半胱氨酸新剂型。     

壳聚糖-三聚磷酸酸钠包载促红细胞生成素对大鼠外伤性脑损伤的作用

目的 研究壳聚糖和三聚磷酸钠(TPP)包载EPO的纳米粒对受伤性脑损伤(TBI)大鼠的作用.方法 用离子交联法,制备壳聚糖(chitosan,CS)-三聚磷酸钠(TPP)/EPO纳米粒,对纳米粒进行表征.TBI大鼠分成4组(每组8只),用PBS、1 mg·mL-1壳聚糖(CS)-TPP 300 μL、200 U·mL-1EPO 300 μL和CS-TPP/EPO 300 μL分别皮下注射,用水迷宫法评价其对脑损伤的作用.结果 壳聚糖-三聚磷酸钠/EPO纳米粒的粒径(348-±8)nm,EPO的包封率为75.16％,在pH 7.4的释放曲线成典型的双相释放.载EPO纳米粒对TBI大鼠作用明显优于对照组.结论 壳聚糖-三聚磷酸钠/EPO纳米粒能显著改善TBI的损伤.     

阿霉素磁纳米脂质体的制备研究

目的采用超小超顺磁纳米粒(USPIOs)作为内部磁性物质,制备阿霉素磁纳米脂质体,并探讨如何得到高效磁包封和药物包封的阿霉素磁纳米脂质体。方法采用逆相蒸发法,以USPIOs为磁核,制备阿霉素磁纳米脂质体,以透射电镜观察到的形态、磁纳米脂质体的粒径、其中包裹的铁含量、药物包封率为指标,考察阿霉素磁纳米脂质体制备时最佳的脂质和磁纳米粒比例。结果当USPIOs用量为1 mg·m L-1时,磷脂用量在6.5 mg·m L-1时,可形成包裹较完全的磁纳米脂质体。得到的磁纳米脂质体粒径为274.3 nm,包裹的铁含量可达(51.43±2.69)%,药物包封率可达(63.38±15.29)%。在4℃条件下放置1个月以内,形态仍较稳定。结论阿霉素磁纳米脂质体的形成与脂质体浓度和磁纳米粒浓度有很大关系,通过摸索条件,可得到最佳磁纳米粒包封率和药物包封率的磁纳米脂质体,这为下一步阿霉素磁纳米脂质体的性质考察奠定基础。     

卵清蛋白壳聚糖纳米粒的制备及其体外性质

目的 制备包载卵清蛋白(OVA)的壳聚糖(CS)纳米粒,考察影响其粒径的因素并进行体外释放及细胞摄取效率的研究.方法 采用离子交联法,以三聚磷酸钠(TPP)为交联剂制备包载OVA的CS纳米粒,以粒径为考察指标,采用单因素实验法,对CS溶液浓度、pH、TPP浓度、CS与OVA质量比、CS与TPP质量比进行考察,确定最佳处...     

雌二醇鼻用壳聚糖纳米粒的制备及体外性质的考察

目的 研究雌二醇壳聚糖纳米粒的理化性质及鼻黏膜吸收动力学。方法 以三聚磷酸钠( TPP) 为交联剂,用生物降解聚合物材料壳聚糖(CS) 制成纳米粒,通过离子凝胶化法制备雌二醇（E2）壳聚糖纳米粒,分别用动态光散射法仪测定了纳米粒的粒径,高速离心法测定其包封率,透析袋法对其体外释放过程进行了研究,采用大鼠在体灌流模型,考察了质量浓度分别为3.86、7.20、24.75、32.74、51.62 mg&;#8226;L^-1的雌二醇壳聚糖纳米粒的鼻黏膜吸收动力学。结果 当m (CS) : m (TPP)在3:1～7:1之间时,可以形成壳聚糖纳米粒,5:1时得到得纳米粒最佳,平均粒径为(279.1±7.2) nm。随着E2质量浓度的增加,包封率有降低的趋势;E2在前2 h内发生突释现象,12 h释放量达80%以上。在循环液体积为5 mL、流速为2.5 mL&;#8226;min^-1下,不同质量浓度的雌二醇壳聚糖纳米粒鼻黏膜吸收速度常数不同,且随药液质量浓度的增加而增大。结论 通过离子凝胶化法制备的壳聚糖纳米粒外观呈半透明状,粒径较为均一,有一定的缓释效果,鼻黏膜吸收具有浓度依赖性,一定质量浓度条件下的吸收动力学过程为符合零级动力学。     

单油酸甘油酯/TPGS/壳聚糖脂质纳米粒提高姜黄素稳定性的研究

目的制备载有姜黄素的单油酸甘油酯(GMO)/聚乙二醇1000维生素E琥珀酸酯(TPGS)/壳聚糖(CS)脂质纳米粒,考察该脂质纳米粒在提高药物稳定性方面的潜能。方法采用乳化-高压均质法制备载有姜黄素的GMO/TPGS/CS脂质纳米粒,对该纳米粒进行粒径及分布、zeta电位、微观形态、物理稳定性、UV-Vis光谱学及体外释放动力学等表征。并以姜黄素水溶液为对照,测定该脂质纳米粒在高温、光照、强碱等条件下的稳定性。结果该纳米粒为球形或类球形,平均粒径为(93.8±2.80)nm,多分散系数为(0.156±0.063),zeta电位为+(16.76±1.52)mV;有良好的物理稳定性;UV-Vis光谱显示,姜黄素可能通过疏水作用结合在纳米粒上,这使得药物产生缓释效果,符合Weibull方程。相比姜黄素水溶液,在高温、光照及强碱等强条件下,包封在纳米粒中的姜黄素降解程度显著减小。结论本试验证明了结合使用GMO/TPGS/CS制备姜黄素脂质纳米粒,可显著提高姜黄素的稳定性。     

利福布汀-PLGA纳米粒的制备

目的:制备利福布汀(RB)-聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,并对制备工艺进行优化。方法:采用改良的自乳化溶剂挥发法制备;通过单因素法考察对包封率影响较大的因素,在此基础上以包封率为指标采用正交设计优化纳米粒的制备工艺并进行验证。结果:对纳米粒包封率影响较大的因素是RB与PLGA投药比、PLGA浓度、混合有机相中丙酮比例及油水相比;上述各因素的最佳水平分别是1:2、40mg·mL-1、70%、1:5。验证试验中所制纳米粒平均粒径为(201±19)nm、包封率为(59.1±5)%、载药量为(15.1±2.4)%。结论:本文的制备方法简单,所得纳米粒粒径小、质量稳定。     

Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles

Chitosan nanoparticles (CS NP) with various formations were produced based on ionic gelation process of tripolyphosphate (TPP) and chitosan. They were examined with diameter 20-200 nm and spherical shape using TEM. FTIR confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. Factors affecting delivery properties of bovine serum albumin (BSA) as model protein have been tested, they included molecular weight (Mw) and deacetylation degree (DD) of chitosan, the concentration of chitosan and initial BSA, and the presence of polyethylene glycol (PEG) in encapsulation medium. Increasing Mws of chitosan from 10 to 210 kDa, BSA encapsulation efficiency was enhanced about two times, BSA total release in PBS (phosphate buffer saline) pH 7.4 in 8 days was reduced from 73.9 to 17.6%. Increasing DD from 75.5 to 92% promoted slightly the encapsulation efficiency and decelerated the release rate. The encapsulation efficiency was highly decreased by increase of initial BSA and chitosan concentration; higher loading capacity of BSA speeded the BSA release from the nanoparticles. Adding PEG hindered the BSA encapsulation and accelerated the release rate.     

Chitosan nanoparticles for plasmid DNA delivery: effect of chitosan molecular structure on formulation and release characteristics

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450-820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential approximately +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation technique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure (p > .05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.     

Design and evaluation of a nanoparticulate system prepared by biodegradable polymers for oral administration of protein drugs

The present work was about the preparation of nanoparticles by a complex coacervation process using the biodegradable polymers Chitosan and sodium alginate and to evaluate their suitability for oral administration of proteins. Bovine serum albumin (BSA) was used as a model protein for incorporation into the nanoparticulate system. The prepared BSA-loaded nanoparticles were characterized for size, morphology, zeta potential, BSA encapsulation efficiency and subsequent release kinetics. The physicochemical characters of the prepared nanoparticles depend mostly on polymers mass ratio, pH of the reaction medium and BSA loading concentration. The minimum average size of empty nanoparticles were found to be 339.80 +/- 02.20 nm and the BSA loaded nanoparticles prepared under varying conditions had average sizes in the range of 473.67 +/- 18.75 nm to 751.33 +/- 6.81 nm, and exhibit a high positive zeta potential. The SEM image showed spherical shaped nanoparticles. By increasing the concentration of BSA from 0.1 mg/ml to 2.8 mg/ml the loading capacity of the nanoparticulate system was increased whereas the encapsulation efficiency was decreased. The results suggest that the nanoparticulate system is a potential carrier for delivering protein drugs.     

川芎嗪壳聚糖纳米粒的制备及体外靶向分布研究

目的：制备川芎嗪壳聚糖纳米粒,考察纳米粒在人癌细胞的靶向分布。方法：以壳聚糖为载体,用离子交联法制备川芎嗪纳米粒。用激光粒度分析仪检测粒径,用透射电镜观察纳米粒的形态。用HPLC法测定纳米粒的包封率、载药量和体外释放度。以川芎嗪溶液为对照,测定纳米粒在人乳腺癌MCF-7细胞株、人肺腺癌A549细胞株和人白血病K562细胞株中的浓度,评价其靶向性。结果：制备的川芎嗪壳聚糖纳米粒为圆球形,平均粒径为（118.6±2.2） nm,分散系数（0.117±0.016）（n=3）,包封率（79.7±0.4）%,载药量（24.3±0.2）%,缓慢释药96 h累积释药率达75%。纳米粒在人乳腺癌MCF-7细胞株、人肺腺癌A549细胞株和人白血病K562细胞株中的浓度显著高于川芎嗪溶液（P＜0.05）。结论：制备的川芎嗪壳聚糖纳米粒对人癌细胞有靶向浓集作用。     

Chitosan Nanoparticles for Plasmid DNA Delivery: Effect of Chitosan Molecular Structure on Formulation and Release Characteristics

Chitosan can be useful as a nonviral vector for gene delivery. Although there are several reports to form chitosan-pDNA particles, the optimization and effect on transfection remain insufficient. The chitosan-pDNA nanoparticles were formulated using complex coacervation and solvent evaporation techniques. The important parameters for the encapsulation efficiency were investigated, including molecular weight and deacetylation degree of chitosan. We found that encapsulation efficiency of pDNA is directly proportional with deacetylation degree, but there is an inverse proportion with molecular weight of chitosan. DNA-nanoparticles in the size range of 450–820 nm depend on the formulation process. The surface charge of the nanoparticles prepared with complex coacervation method was slightly positive with a zeta potential of +9 to +18 mV; nevertheless, nanoparticles prepared with solvent evaporation method had a zeta potential ～ +30 mV. The pDNA-chitosan nanoparticles prepared by using high deacetylation degree chitosan having 92.7%, 98.0%, and 90.4% encapsulation efficiency protect the encapsulated pDNA from nuclease degradation as shown by electrophoretic mobility analysis. The release of pDNA from the formulation prepared by complex coacervation was completed in 24 hr whereas the formulation prepared by evaporation tecnique released pDNA in 96 hr, but these release profiles are not statistically significant compared with formulations with similar structure p >. 05). According to the results, we suggest nanoparticles have the potential to be used as a transfer vector in further studies.     

黄芩素固体脂质纳米粒包封率测定及体外释放度考察

目的测定黄芩素固体脂质纳米粒的包封率,并考察其体外释放规律。方法溶剂扩散法制备脂质纳米粒,高速离心法分离纳米粒和游离药物,HPLC法测定包封率并考察其体外释放规律。结果测得纳米粒的平均包封率为60.73%,其体外释放规律符合H iguch i动力学方程。结论黄芩素固体脂质纳米粒有较高的包封率,在体外具有良好的缓释作用。     

Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods

The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also measured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle surfaces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus.     

Encapsulation and controlled release of recombinant human erythropoietin from chitosan-carrageenan nanoparticles

Novel chitosan-carrageenan nanoparticles were produced through the process of ionotropic gelation for the encapsulation and controlled release of recombinant human erythropoietin (rHu-EPO). The effects of chitosan concentration, chitosan to carrageenan mass ratio and solution pH on the nanoparticle diameter, polydispersity and surface charge were explored through both screening and response surface modeling (RSM) methods. The chitosan-carrageenan nanoparticles created had particle diameters between 200 and 1000nm, surfaces charges between 40 and 55mV, and polydispersity between 0.2 and 0.35. RSM optimized chitosan-carrageenan nanoparticles demonstrated an increased rHu-EPO encapsulation efficiency of 47.97?4.10% and a more sustained in vitro release of ~50% over a 2 week period when compared to previous nano/microparticle delivery systems. Studies on the effect of surface charge and chitosan molecular weight on the encapsulation and controlled release of rHu-EPO revealed that increasing either led to improved encapsulation efficiency and reduced release rate.     

Microencapsulation of hemoglobin in chitosan-coated alginate microspheres prepared by emulsification/internal gelation

Chitosan-coated alginate microspheres prepared by emulsification/internal gelation were chosen as carriers for a model protein, hemoglobin (Hb), owing to nontoxicity of the polymers and mild conditions of the method. The influence of process variables related to the emulsification step and microsphere recovering and formulation variables, such as alginate gelation and chitosan coating, on the size distribution and encapsulation efficiency was studied. The effect of microsphere coating as well its drying procedure on the Hb release profile was also evaluated. Chitosan coating was applied by either a continuous microencapsulation procedure or a 2-stage coating process. Microspheres with a mean diameter of less than 30 microm and an encapsulation efficiency above 90% were obtained. Calcium alginate cross-linking was optimized by using an acid/CaCO(3) molar ratio of 2.5, and microsphere-recovery with acetate buffer led to higher encapsulation efficiency. Hb release in gastric fluid was minimal for air-dried microspheres. Coating effect revealed a total release of 27% for 2-stage coated wet microspheres, while other formulations showed an Hb release above 50%. Lyophilized microspheres behaved similar to wet microspheres, although a higher total protein release was obtained with 2-stage coating. At pH 6.8, uncoated microspheres dissolved in less than 1 hour; however, Hb release from air-dried microspheres was incomplete. Chitosan coating decreased the release rate of Hb, but an incomplete release was obtained. The 2-stage coated microspheres showed no burst effect, whereas the 1-stage coated microspheres permitted a higher protein release.