半乳糖化阿霉素白蛋白纳米粒的制备及其质量评价

目的:制备半乳糖化阿霉素白蛋白纳米粒,并考察了其形态、粒径、载药量、包封率和体外释药特性.方法:采用相分离法制备阿霉素白蛋白纳米粒,并在其表面偶联半乳糖苷,使之成为半乳糖化白蛋白纳米粒.激光扫描电子显微镜观察纳米粒的形态,马尔文激光粒度仪测定其粒径分布.采用紫外分光光度法测定纳米粒的载药量和包封率,并初步研究其体外释药特性.结果:电镜结果显示阿霉素纳米粒呈类球型,平均粒径为316.3 nm,纳米粒载药量为3.12%,包封率达91.82%,48 h体外累积释药率为55.71%.结论:本方法制备阿霉素纳米粒工艺简单且包封率较高.体外释药结果显示半乳糖化阿霉素白蛋白纳米粒具有明显的缓释作用.     

环索奈德纳米粒制备及其性质

目的:制备环索奈德固体脂质纳米粒胶体溶液,对其理化性质进行考察。方法:经方法考察,确定采用乳化-溶剂挥发法制备环索奈德纳米粒胶体溶液。在载体材料种类及用量、表面活性剂种类及用量、水相用量等单因素考察基础上,对处方组成进行了响应面优化,确定了最佳处方组成和制备工艺。用高速冷冻离心法和紫外分光光度法测定了包封率、载药量,激光粒径仪测定了粒径、Zeta电位,扫描电镜观察了纳米粒形态,并考察了药物纳米粒胶体溶液的体外稳定性。结果:乳化-溶剂挥发法适合制备环索奈德纳米粒胶体溶液,载体材料组成、药物与载体材料质量比、表面活性剂用量对其粒径影响较大。最佳处方制备的纳米粒呈圆整球状,平均粒径为(96.6±18.4)nm,Zeta电位为(-12.7±2.2)mV,包封率为(94.3±1.4)%,载药量为(10.72±0.23)%,纳米粒溶液在室温条件下不够稳定。结论:研究中处方及制备工艺适合制备环索奈德纳米粒胶体溶液,相关理化性质检测方法可行。     

醋酸地塞米松脂质纳米粒的优化处方及制备工艺

目的:制备一种具有较高载药量,避免药物突释,达到缓释的新型醋酸地塞米松脂质纳米粒.方法:利用薄膜-超声法,使用卵磷脂和大豆油作为载体材料,制备醋酸地塞米松脂质纳米粒.以纳米粒的粒径、Zeta电位、载药量和包封率作为考察指标,对有机溶剂的种类、投药量、载体材料投料比、表面活性剂种类、表面活性剂用量和超声时间进行筛选,并进行体外释放研究.结果:最终确定最优处方及制备工艺为醋酸地塞米松15 mg,大豆油100 mg,卵磷脂100mg,二氯甲烷20 mL,4%的聚山梨酯80和4%的泊洛沙姆188各10 mL,超声时间5 min.结论:该处方制备的纳米粒不仅可提高醋酸地塞米松的载药量和包封率,且可避免药物的突释现象,为其纳米新剂型的制备提供了新方法.     

5-氟尿嘧啶共聚物纳米粒的制备及其药剂学性质

目的 以生物可降解材料Pluronic P105-PAGA共聚物制备5-氟尿嘧啶(5-FU)纳米粒,并考察纳米粒的药剂学特性.方法 采用透析法制备纳米粒,以包封率和载药量为指标,应用星点设计效应面优化法优化处方,并考察其表面特征、包封率、载药量、粒径、体外释放等性质.结果 5-FU-Pluronic P105-PAGA纳米粒为圆整的类球形实体粒子,平均粒径为175 nm,载药量为22.37%,包封率为95.26%,有突释现象,体外12 h累积释放率为80.4%.结论 所制纳米粒具有高包封率和载药量,粒径适宜,具有一定的缓控释作用.     

莪术油固体脂质纳米粒的制备

目的研究影响莪术油固体脂质纳米粒制备的主要因素。方法采用高压均质法制备莪术油固体脂质纳米粒混悬液,以单因素考察和正交设计法筛选出比较理想的处方和工艺,并考察其形态、粒径、载药量及包封率。结果所制得的固体脂质纳米粒为圆整的类球形实体粒子,表面光滑,平均粒径为80.3nm,载药量为11.82%,包封率为81.75%。结论高压均质法可用于莪术油类液体药物固体脂质纳米粒的制备。     

卡莫氟固体脂质纳米粒的制备及工艺研究

目的:制备卡莫氟固体脂质纳米粒并考察其药剂性质。方法:采用高压均质法制备卡莫氟固体脂质纳米粒混悬液,以单因素考察和正交设计法筛选处方和工艺,并考察其形态、粒径、载药量及包封率。结果:优选出的较佳处方大豆卵磷脂、泊洛沙姆188、吐温-80和硬脂酸用量分别为8.0、12.0、1.0、7.5mg·mL-1;所制得的固体脂质纳米粒为圆整的实体粒子,表面光滑,平均粒径为78.7nm,载药量为23.47%,包封率为82.33%。结论:高压均质法可用于卡莫氟类脂溶性药物固体脂质纳米粒的制备。     

人参皂苷Rd固体脂质纳米粒的制备

目的:制备人参皂苷Rd固体脂质纳米粒,并考察其理化性质。方法:从旋转薄膜-超声分散法、乳化蒸发-低温固化法、高剪切乳化超声法和高压乳匀法中优选出制备方法;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,采用正交试验设计,确定最佳处方组成和制备工艺条件;用凝胶柱色谱和HPLC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Zeta电位。结果:脂质、表面活性剂、助表面活性剂和主药的用量对Rd固体脂质纳米粒的粒径、Zeta电位和包封率均有不同程度的影响。高压乳匀法适合制备Rd固体脂质纳米粒。纳米粒表面呈圆整的球状,大小相近,分散均匀;平均粒径为(102.7±27.0)nm,Zeta电位为(-44.9±9.5)mV,包封率和载药量分别为(81.8±2.6)%和(6.37±0.21)%(n=3)。纳米粒稳定性良好,在4℃下保存4周后,粒径和包封率变化不明显。结论:高压乳匀法适合制备人参皂苷Rd固体脂质纳米粒,工艺稳定可行。     

苦参素磷脂纳米粒的研制

目的:制备稳定性好、亲和力强的苦参素大豆磷脂纳米粒(KU-PL-NP).方法:利用大豆磷脂为载体,采用薄膜-超声分散法制备了苦参素大豆磷脂纳米粒,以制剂的含量测定、载药量、包封率及粒径为主要评价指标.结果:3批制剂平均包封率为64.05%,平均载药量为21.4%,平均粒径为309.5 nm.结论:苦参素大豆磷脂纳米粒基本达到设计要求,该制剂有望成为一种新的药物靶向载体系统.     

多西紫杉醇白蛋白纳米粒的制备及体外评价

目的：制备多西紫杉醇白蛋白纳米粒，考察白蛋白和多西紫杉醇的处方量及乙醇加入量等因素对其形态、粒径、Zeta电位、收率、包封率、载药量和体外释药特性的影响，并对处方工艺进行优化。方法：采用去溶剂化-化学交联法制备多西紫杉醇白蛋白纳米粒，透射电镜观察纳米粒形态，马尔文激光粒度仪测定其粒径分布及Zeta电位，考马斯亮兰-酶标仪法测定纳米粒收率，HPLC法测定纳米粒包封率和载药量；以累积释药百分率为指标，通过方程拟合释药曲线，考察制剂的体外释药特性。处方优化采用星点设计-效应面优化法，应用SAS统计软件对数据进行处理。结果：优化处方制得的纳米粒为类球形，平均粒径65．3nm，Zeta电位-31．4mV，纳米粒收率95．0％，包封率74．3％，载药量4．65％，制剂24小时体外累积释药百分率为74．4％。结论：难溶性抗癌药物多西紫杉醇可以采用去溶剂化-化学交联法制备成白蛋白纳米粒，其粒径小，稳定性高，可显著提高多西紫杉醇在水相中的浓度。其优化处方中药物的释放显著慢于原料药磷酸盐缓冲溶液的释放，具有缓释效果。     

胰岛素纳米粒温敏凝胶的制备及体外释药性能

目的:制备胰岛素壳聚糖温度敏感型原位凝胶(INS-CS-NP-TISG)并进行体外释药动学考察。方法:采用离子凝胶化法制备胰岛素壳聚糖纳米粒;均匀设计法优化其处方及制备工艺,观察形态,测定粒径、表面电位、包封率和载药量;冷法配液的方法制备温度敏感型原位凝胶,改进透析袋-恒温水浴法研究胰岛素壳聚糖纳米粒温度敏感型原位凝胶溶液的体外释药动学。结果:优化制得的纳米粒呈类球形,均匀圆整,分散性好;平均粒径为(255.3±143.5)nm,在175.2~349.6nm范围内的纳米粒子达99.4%,大小均匀,分布较窄;高效液相色谱法(HPLC)测定胰岛素壳聚糖纳米粒平均包封率和载药量分别为75.84%与58.52%;表面电位(ζ)为+32.67;在人工鼻黏液中,胰岛素壳聚糖纳米粒温度敏感型原位凝胶的体外释药符合双相动力学方程,且持续释药24h。结论:选用合适的处方制备胰岛素壳聚糖纳米粒温度敏感型原位凝胶,方法简便,药物载药量高,具有较好的生物黏附性,并有一定的缓释作用。     

Preparation and characterization of sodium ferulate entrapped bovine serum albumin nanoparticles for liver targeting

Sodium ferulate (SF) loaded nanoparticles were prepared by desolvation procedure and subsequent cross-linking of the wall material of bovine serum albumin (BSA). Several factors in the nanoencapsulation process, such as the addition rate of the desolvation agent, composition of BSA and SF solution, amount of the cross-linker glutaraldehyde, were investigated to elucidate their influences on the particle size, zeta potential, drug loading and encapsulation efficiency of the resulted nanoparticles. The obtained spherical nanoparticles were negative charged with zeta potential from -20 to -40 mV, and characterized between 100 and 200 nm with a narrow size distribution. In the condition of introducing 1.0 mL 8% glutareldehyde per mg of BSA, the drug entrapment efficiency (EE) of 80% (w/w) and loading capacity of about 16% (w/w) could be achieved for the cross-linked BSA nanoparticles with SF encapsulated (SF-BSA-NP). And the drug EE was decreased along with the increasing amount of glutareldehyde used for cross-linking. The in vitro drug release properties of SF-BSA-NP behaved with an initial burst effect and then sustained-release stage. To some extent, the drug release rate could be adjusted by cross-linking with different amount of glutaraldehyde. Compared with SF solution, SF-BSA-NP showed a much higher drug distribution into liver and a lower drug concentration in other tissues, after intravenously injected to mice. So, BSA based nanoparticles might be a suitable controlled released carrier for the freely water-soluble drug SF and further hepatic targeted drug delivery.     

制备工艺对多柔比星白蛋白纳米粒理化性质、体外释放及药动学的影响

分别采用去溶剂化法和乳化交联法制备多柔比星牛血清白蛋白(BSA)纳米粒,以BSA收率、包封率、载药量和粒径等为评价指标,优选处方工艺,并比较两种制备工艺所得制品的差异.结果表明,去溶剂化法和乳化交联法所得纳米粒外观均呈球形,差异不大,BSA收率、包封率、载药量、粒径及ζ电位分别为96.5％、92.9％,98.5％、97.4％,4.3％、3.6％,132.4、172.9 nm,-27.7、-19.9 mV.但制备工艺对体外释放行为和大鼠体内药动学行为影响较大,去溶剂化法和乳化交联法制备的多柔比星BSA纳米粒在生理盐水中48 h累积释放率分别为44.2％、63.8％;大鼠尾静脉给药后,去溶剂化法和乳化交联法所得制品的AUC分别是原药的1.5倍(P＜0.05)和1.1倍(P＞0.05),前法所得纳米粒在大鼠体内具有一定的缓释效果,而后法所得制品没有.     

Mannose 6‐phosphate‐modified bovine serum albumin nanoparticles for controlled and targeted delivery of sodium ferulate for treatment of hepatic fibrosis

Objectives The aim was to prepare neoglycoprotein‐based nanoparticles for targeted drug delivery to hepatic stellate cells, and to evaluate their characteristics in vitro and in vivo. Methods The neoglycoprotein of bovine serum albumin modified with mannose 6‐phosphate was synthesised from mannose, and used as wall material to nanoencapsulate the model natural antifibrotic substance sodium ferulate using a desolvation method. The morphology, drug loading capacity, release in vitro and biodistribution in vivo of the nanoparticles were studied. Selectivity of the nanoparticles for hepatic stellate cells was evaluated by immunohistochemical analysis of fibrotic rat liver sections. Key findings The spherical nanoparticles were negatively charged with zeta potential ranging from ?2.73 to ?35.85 mV, and sizes between 100 and 200 nm with a narrow size distribution. Drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) could be achieved. In vitro, the nanoparticles showed an initial rapid continuous release followed by a slower sustained release. After intravenous injection into mice, the nanoparticles showed a slower elimination rate and a much higher drug concentration in liver compared with the sodium ferrate solution, and less distribution to the kidneys and other tissues. Immunohistochemistry indicated that the neoglycoprotein‐based nano‐particles were taken up specifically by hepatic stellate cells. Conclusions The nanoparticles may be an efficient drug carrier targeting hepatic stellate cells.     

Preparation and characterization of galactosylated bovine serum albumin nanoparticles for liver-targeted delivery of oridonin

In this study, galactosylated bovine serum albumin (GB), which could be developed for a liver targeting carrier was synthetized and it was identified by Fourier transform infrared (FT-IR) spectrometer. Oridonin loaded bovine serum albumin nanoparticle (ORI-BSA-NP) and oridonin loaded GB nanoparticle (ORI-GB-NP) were prepared and optimized by the desolvation technique. During the preparation of ORI-GB-NP, galactosamine was introduced to end-cap the free aldehyde groups on nanoparticles. The characteristics of ORI-GB-NP such as particle size, zeta potential, particle morphologie, entrapment efficiency and drug loading were evaluated. The nearly spherical nanoparticles, with a narrow size distribution below 200 nm, were negatively charged with zeta potential of about −30 mV. Meanwhile, differential scanning calorimetry (DSC) and X-ray diffraction confirmed the amorphous state of ORI in ORI-GB-NP. The in vitro drug release of ORI from ORI-GB-NP presented a biphasic pattern with an initial burst effect and consequently sustained release. These results implied that the nanoparticles possessed fine physicochemical characteristics and seemed to be a stable delivery system for poorly soluble oridonin.     

Effect of surfactant on fabrication and characterization of paclitaxel-loaded polybutylcyanoacrylate nanoparticulate delivery systems

The feasibility of applying biodegradable polybutylcyanoacrylate (PBCA) nanoparticulate delivery systems (NDSs) for the controlled release of paclitaxel was investigated. Paclitaxel-loaded and unloaded PBCA-NDSs containing various surfactants (dextran 70, cholesterol, polyvinyl alcohol and lecithin) were prepared by anionic polymerization. The effects of surfactant (1% w/v), surfactant combination (1% w/v each), and surfactant concentration (0.05, 1.0 and 2.5% w/v) on PBCA-NDSs were evaluated and characterized by particle size, zeta potential, entrapment efficiency, and in-vitro paclitaxel release kinetics. The physicochemical characteristics of PBCA-NDSs incorporated with various surfactants were significantly improved compared with PBCA-NDS without any surfactant, by decreasing particle size at least 3-fold as well as by increasing the zeta potential up to 18-fold to minimize the agglomeration of nanoparticles. Moreover, PBCA-NDSs incorporated with various surfactants demonstrated higher entrapment efficiency of paclitaxel. Results from the in-vitro release kinetic studies indicated that a more controlled biphasic zero-order release pattern of paclitaxel was observed for PBCA-NDSs incorporated with various surfactants. Compared with dextran 70 and polyvinyl alcohol, the naturally occurring lipids, lecithin and cholesterol, indicated greater advantages in improving the physicochemical properties of PBCA-NDSs, in terms of smaller particle size, higher zeta potential and better drug entrapment efficiency, and better controlled release of paclitaxel, in terms of lower release rate and prolonged action from PBCA-NDSs.     

采用星点设计-效应面法优化及制备阿霉素白蛋白纳米粒

目的采用星点设计-效应面法优化阿霉素白蛋白纳米粒的制备工艺。方法采用去溶剂化-固化交联法制备阿霉素白蛋白纳米粒。以白蛋白质量浓度(X1:1ρ,g.L-1)、阿霉素的质量浓度(X2:2ρ,g.L-1)、pH值(X3)及白蛋白理论交联度(X4,%)为考察对象,以纳米粒平均粒径(Y1:d,nm)、zeta电位(Y2:V,mV)、载药量(Y3:w1,%)和包封率(Y4:w2,%)为评价指标,以四因素五水平的星点设计-效应面法筛选出最佳制备工艺;并采用透射电镜观察制得纳米粒的形态。结果优化后的处方工艺为:白蛋白质量浓度为17 g.L-1、阿霉素质量浓度为2 g.L-1、pH值为9、白蛋白理论交联度为125%。以此条件制得的纳米粒平均粒径为(151±0.43)nm,zeta电位为-(18.8±0.21)mV,载药量为(21.4±0.70)%,包封率为(76.9±0.21)%,均与预测值偏差较小。结论阿霉素白蛋白纳米粒的制备采用星点设计-效应面法设计并优化是可行的。     

叶酸介导表没食子儿茶素没食子酸白蛋白纳米粒的制备及其体外靶向性与活性评价

研究能主动靶向于前列腺癌细胞PC-3的表没食子儿茶素没食子酸 (EGCG) 白蛋白 (BSA) 纳米粒的制备工艺与体外靶向性和活性评价。去溶剂法制备叶酸介导EGCG白蛋白纳米粒 (FA-EGCG-BSANP), 采用原子力显微镜 (AFM) 观察纳米粒形状和粒径, HPLC测定EGCG的载药量和包封率, 紫外分光光度法测定叶酸偶联量, 以激光共聚焦和荧光分光光度计测定FA-EGCG-BSANP对PC-3细胞的靶向性, 用MTT法测定其体外活性。所得FA-EGCG-BSANP的平均粒径为200 nm左右, 分布均匀; EGCG的包封率可达 (81.5 ± 1.8) %, 载药量为 (29.3 ± 0.6) %, 叶酸偶联量为18.363 μg·mg⁻¹ BSA;PC-3细胞对FA-EGCG-BSANP的摄取量为EGCG-BSANP的23.65倍, 并且呈现较强的浓度依赖性; 同等浓度下FA-EGCG-BSANP对PC-3细胞的抑制率为82.8%, 而EGCG溶液和EGCG-BSANP分别为58.6%和55.1%, 并且抑制率与PC-3细胞对这些纳米粒的摄取能力呈正相关。FA-EGCG-BSANP能明显提高EGCG对PC-3细胞的靶向效果,并提高了对细胞的致死作用,从而提高了EGCG作为一种潜在抗癌药物的治疗效果,为进一步探索该纳米粒在体内的靶向性、活性和代谢规律提供了实验基础。     

星点设计-效应面法优化穿心莲内酯固体脂质纳米粒处方

以高压均质法制备穿心莲内酯固体脂质纳米粒。采用星点设计考察药物与脂质材料(即单硬脂酸甘油酯与山嵛酸甘油酯的1∶1混合物)比例、卵磷脂与脂质材料比值及表面活性剂(吐温-80)浓度对包封率和载药量的影响,并对结果进行多元线性和二项式方程拟合,用效应面法预测最佳处方。结果表明,载药量的多元线性回归拟合方程具有良好的相关性,而包封率的二项式拟合方程优于多元线性回归拟合方程。优化处方为药脂比9%、卵磷脂与脂质材料比值为1.6、吐温-80浓度为3%。优化后固体脂质纳米粒的包封率和载药量分别为(91.0±0.9)%和(3.49±0.03)%,粒径为(286.3±8.0)nm,电位为(-20.6±0.2)mV。     

HPLC法测定马钱子碱固脂纳米粒冻干粉的包封率和载药量

目的：测定马钱子碱固脂纳米粒冻干粉的包封率和载药量。方法：采用SephadexG-50凝胶柱分离固脂纳米粒和游离马钱子碱,高效液相色谱法测定包封率和载药量,并进行方法学考察。结果：葡聚糖凝胶柱能有效分离固脂纳米粒与游离马钱子碱,平均柱回收率和平均柱加样回收率分别为97．2％和96．4％。马钱子碱固脂纳米粒冻干粉的平均包封率为50．18％,平均载药量为2．11％。结论：该方法简便易行,准确可靠,重复性好,可用于马钱子碱田脂纳米粒冻千粉的载药量和包封率的测定。     

Poly(D,L-lactide-co-glycolide) protein-loaded nanoparticles prepared by the double emulsion method--processing and formulation issues for enhanced entrapment efficiency

Although extensive research in the field of biodegradable microparticles containing peptide or protein drugs has greatly advanced production know-how, the effects of critical parameters influencing successful drug entrapment have not yet been sufficiently investigated with nano-scaled carriers. This paper deals with the formulation and processing parameters of the w(1)/o/w(2) double emulsion method that can affect nanoparticle size and loading. Fluorescein isothiocyanate-labelled bovine serum albumin (FITC-BSA) was used as a model protein. Results showed that high FITC-BSA entrapment efficiencies were reached (>80%) when sonication was used for the two emulsification steps of the nanoparticle formation, independently of the mixing durations and intensities. By comparison, the use of a vortex mixer for obtaining the primary w(1)/o emulsion led to a rather poor entrapment efficiency (approximately 25%). Some inherent properties of the poly(D,L-lactic-co-glycolic acid) polymer, such as, for example, high molecular weight, high hydrophilicity or the presence of free carboxylic end groups, enhanced the drug entrapment efficiency. It was also demonstrated that a low nominal drug loading, a large volume of the inner w1 phase or the choice of methylene chloride instead of ethyl acetate as organic solvent favoured the drug entrapment, with entrapment efficiency values often reaching 100%. However, when using methylene chloride, the mean particle size was substantially increased, due to the presence of larger particles. Mean particle size increased also when the polymer concentration in the organic phase was increased.