乳化蒸发法制备固体脂质纳米粒

目的：采用乳化蒸发法制备固体脂质纳米粒,并考察其载药性能。方法：对影响固体脂质纳米粒质量的工艺因素和处方因素进行考察和优化设计,得到最优处方。选用模型药物酮洛芬制备载药固体脂质纳米粒,考察其包封率和体外释放行为。结果：所得固体脂质纳米粒平均粒径为（228.2±18.1）nm,多分散系数为（0.217±0.022）,ξ电位为-（21.4±0.6）mV。载药固体脂质纳米粒最佳包封率为（64.1±3.3）%,体外释放行为符合Weibull模型。结论：采用乳化蒸发法制备固体脂质纳米粒是可行的。     

雷公藤内酯醇固体脂质纳米粒的制备及理化性质

目的：以聚乙二醇单硬脂酸酯表面修饰材料结合到固体脂质纳米粒（solid lipid nanoparticles,SLN）,以雷公藤内酯醇（triptolide,TPL）为模型药,制备一种具有良好亲水亲脂性的雷公藤内酯醇固体脂质纳米粒。方法：采用熔融-乳化法制备固体脂质纳米粒。通过单因素考察、中心复合设计（central composite design,CCD）,考察脂质材料、聚山梨醇酯-80和PEG-stearate（PEG-SA）三个因素对TPL-SLN粒径、包封率和载药量的影响。通过透射电镜、热分析和X-射线衍射考察TPL-SLN的理化性质,并考察其固体脂质纳米粒的稳定性以及体外释放情况。用MTT法测定其对人正常肝L02细胞和肝癌细胞HepG2的增殖抑制作用并计算其IC₅₀。结果：最优的处方：脂质材料为7.5%,聚山梨醇酯80（Tween 80）为2%和PEG-SA为2%,其粒径（193.43±6.07）nm,包封率（87.63±0.09）%,载药量（0.33±0.01）%。透射电镜观察所制备的纳米粒的形态近似于球形,DSC分析和X-射线衍射证实TPL以非晶型的形式存在于固体脂质纳米粒中。稳定性考察发现纳米粒粒径在一个月的贮存期基本没有变化（P>0.05）,体外释放表明TPL-SLN具有体外缓释特性。TPL-SLN对肿瘤细胞的抑制作用强于正常肝细胞。结论：雷公藤内酯醇聚乙二醇修饰固体脂质纳米粒有望开发为临床口服用药新剂型。     

汉黄芩素固体脂质纳米粒的制备及体外释放度考察

目的:制备汉黄芩素固体脂质纳米粒并对其体外释放度进行考察.方法:采用乳化分散-超声法制备汉黄芩素固体脂质纳米粒,以包封率和载药量为评价指标,进行正交试验筛选最优处方,并对最优处方的外观、粒径和体外释放度进行考察.结果:制得的纳米粒为均一球形,平均粒径为(153 ±34)nm,其平均载药量为(60.53±2.17)％,平均包封率为(85.54±4.16)％,48 h累积释放达80％.结论:本试验获得了较理想的汉黄芩素固体脂质纳米粒,其体外释放具有缓释作用.     

超临界辅助喷雾法用于固体脂质纳米粒的制备

目的采用超临界辅助喷雾制粒法制备固体脂质纳米粒,并考察工艺与处方因素对纳米粒理化性质的影响。方法采用自制超临界喷雾制粒设备,制备硬脂酸脂质纳米粒,考察硬脂酸浓度、超临界流体CO2与载体溶液流量比、喷嘴孔径等对固体脂质纳米粒粒径的影响,筛选合适的处方工艺参数;以亲水性大分子药物胰岛素为模型药物,制备载药固体脂质纳米粒,评价纳米粒的粒径、电位、包封率、释放度等理化性质。结果制备得到的纳米粒粒径与载体浓度、超临界流体CO2与载体溶液流量比、喷嘴孔径有关,通过处方工艺的调节,可制得平均粒径〈300nm的固体脂质纳米粒;制得的胰岛素固体脂质纳米粒的平均粒径约300nm,包封率72．2％,载药量为3．44％,载药纳米粒在体外可实现12h缓慢释放;处方中加入泊洛沙姆可减小纳米粒粒径和粒度分布,但药物的包封率降低,并且突释现象更明显。结论超临界辅助喷雾制粒法可用于固体脂质纳米粒的制备,并能够对亲水性药物实现有效的包封和释放的调节。     

吡喹酮固体脂质纳米粒的制备及其理化性质研究

目的:制备吡喹酮固体脂质纳米粒(PZQ-SLN),并考察其理化性质。方法:以山嵛酸甘油酯和乙酸丁酯为脂质材料,超声分散法制备PZQ-SLN,透射电镜观察纳米粒形态,测定其粒径、Zeta电位和药物包封率,并进行体外释放试验及考察样品的稳定性。结果:所得脂质纳米粒为类圆球状,粒径分布较均匀。样品粒径为(100±21)nm,包封率为(79.3±0.69)%,平均Zeta电位值为—66.3mV。药物体外释放符合Weibull方程。4℃放置3mo后粒径、包封率和Zeta电位均无明显变化。结论:制备的PZQ-SLN理化性质较为理想,能使药物缓慢释放。4℃条件下贮存比较稳定。     

薄膜-超声法制备芦丁固体脂质纳米粒的研究

目的优化薄膜-超声法制备芦丁固体脂质纳米粒的处方。方法以包封率为指标,采用正交设计优化法考察硬脂酸和大豆卵磷脂的用量、吐温-80和聚乙二醇-400的体积分数对包封率的影响,优选最佳处方。用透射电镜观察外观形态,用电位/纳米粒度分析仪分析纳米粒的粒径及Zeta电位,用透析法评价体外释药特征。结果以最佳处方制备的芦丁固体脂质纳米粒呈类球形,平均粒径为195.8±11nm,Zeta电位为-20.65±0.6mV,平均包封率为86.31%,72h体外累积释放87.32%。结论按最佳处方工艺制备的芦丁固体脂质纳米粒具有较高的包封率和较好的缓释效果。     

大黄素固体脂质纳米粒的制备及理化性质研究

目的：制备大黄素固体脂质纳米粒,并对其理化性质进行研究。方法：用乳化一溶剂挥发法制得大黄素素固体脂质纳米粒,并对其粒径、形态、表面电位、包封率、体外释药性质等进行研究。采用全体液平衡反向透析法研究体外释药性质。结果：所制固体脂质纳米粒外观形态圆整,粒度分布均匀,平均粒径为253nm,电位为一25．4mV,包封率为（56．31±2．06）％。药物体外释放符合Weibull线性方程。结论：固体脂质纳米粒可作为大黄素新型缓释给药系统。     

吡喹酮固体脂质纳米粒的研制

目的采用超声分散法制备吡喹酮固体脂质纳米粒,并考察制备过程中的主要影响因素。方法首先通过试验确定制备工艺参数,然后考察各处方因素对粒径大小和稳定性的影响,最后以包封率为评价指标,采用正交实验设计法确定最优处方。结果透射电镜测得纳米粒为类圆球状,粒径分布较均匀。动态光散射法测得样品的粒径为(100±21)nm,包封率为(79.3±0.69)%,平均zeta电位值为-66.3 mV。结论以山嵛酸甘油酯和乙酸丁酯为脂质材料,豆磷脂、泊洛沙姆188和硬脂酸钠为复配乳化剂,采用超声分散法可以简便、快速制得吡喹酮固体脂质纳米粒。     

正交设计优化伊曲康唑固体脂质纳米粒的处方组成与制备工艺

目的:制备伊曲康唑固体脂质纳米粒(itraconazole solid lipid nanoparticles,ITZ-SLNs)并对其进行物相分析以确定纳米粒的形成。方法:以伊曲康唑(ITZ)为模型药物,硬脂酸为载体材料,采用乳化-低温固化法制备伊曲康唑固体脂质纳米粒(ITZ-SLN),正交试验设计优化处方组成和制备工艺,并对纳米粒的结构形态、粒径、表面电位、包封率、体外释药特性等进行了研究。结果: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,Zeta电位为-(37.06±0.53)mV,包封率为(92.11±1.60)%,药物体外释放符合Higuchi方程,经DSC分析证明纳米粒确已形成。结论:伊曲康唑固体脂质纳米粒有望成为新型缓释纳米给药系统。     

蓝萼甲素固体脂质纳米粒的制备及理化性质研究

目的:制备蓝萼甲素固体脂质纳米粒,并对其理化性质进行研究。方法:用乳化-溶剂挥发法制得蓝萼甲素固体脂质纳米粒,并对其粒径、形态、表面电位、包封率、体外释药性质等进行研究。结果:所得蓝萼甲素固体脂质纳米粒的粒径分布均匀,平均粒径为(190±10·3)nm,Zeta电位为—31·2mV,平均包封率为(50·45±0·804)%;药物体外释放符合Higuchi线性方程,具有显著缓释作用。结论:固体脂质纳米粒可作为蓝萼甲素新型缓释给药系统。     

Preparation and characterization of solid lipid nanoparticles containing peptide

Solid lipid nanoparticles (SLN) are an alternative colloidal carrier system for controlled drug delivery. However, only a few have been studied regarding the incorporation of peptides into SLN, due to the hydrophilic peptide not easy to enter the lipophilic matrix of SLN. In the present report, peptide-loaded solid lipid nanoparticles were prepared by a novel solvent diffusion method in an aqueous system. The model peptide gonadorelin was incorporated to study the entrapment efficiency, size, zeta potential (charge) and drug delivery characterization. Gonadorelin and monostearin were dissolved in acetone and ethanol at 50 degrees C in water bath, the resultant organic solution was poured into an aqueous containing 1% polyvinyl alcohol (PVA) under mechanical agitation. The peptide-loaded solid lipid nanoparticles were quickly produced and separated by centrifugation. The average volume diameter of gonadorelin-loaded SLN is 421.7 nm and the zeta potential of SLN is -21.1 mV dispersed in distilled water. Up to 69.4% of gonadorelin can be incorporated. In vitro release of gonadorelin from SLN is slow. In the test solution of a 0.1N hydrochloric acid for 2h and then transferred in a pH 6.8 phosphate buffer (simulative gastrointestinal fluid), the drug-release behavior from SLN suspension exhibited a biphasic pattern. After burst drug-release at the first 6h at a percentage of 24.4% of loaded gonadorelin, a distinctly prolonged release over a monitored period of 12 days was observed and nearly 3.81% of drug was released in each day. In the test solution of a pH 6.8 phosphate buffer (simulative intestinal fluid), the drug-release rate from SLN was similar to that in the simulative gastrointestinal fluid. Further, a novel preparation method in the present research for peptide-loaded SLN was established. These results also demonstrate the principle suitability of SLN as a prolonged release formulation for hydrophilic peptide drugs.     

Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers

Background and the purpose of the study

Domperidone (DOM) is a dopamine- receptor (D₂) antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN) and Nanostructured Lipide Carrier (NLC). The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN) and DOM loaded nanostructured lipid carriers (DOM-NLC).

Methods

DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99%) and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM). SLN and NLC formulations were subjected to stability study over a period of 40 days.

Results

The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1) and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84% and 32.23 nm, 0.160, 10.47 mV, 90.49% respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P<0.05) change in particle size, zeta potential, PDI and entrapment efficiency indicating the developed SLN and NLC were fairly stable.

Conclusion

Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could be prepared by hot homogenization followed by ultrasonication technique.     

Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles

A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(?)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25°C and 4°C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.     

香叶木素固体脂质纳米粒的制备及质量评价

目的 制备香叶木素固体脂质纳米粒并对其进行质量评价。方法 采用溶剂注入法制备香叶木素固体脂质纳米粒,用 Box-Benhnken效应面法优化处方,并通过包封率、微观形态、粒径分布和Zeta电位对香叶木素固体脂质纳米粒的质量进行评价。 结果 香叶木素固体脂质纳米粒最优处方组成：表面活性剂浓度3.39%,棕榈酸浓度0.116%,脂药质比为21:100,制备的香叶木素 固体脂质纳米粒外观澄清透明,带淡蓝色乳光;平均粒径为(91.73±3.18)nm(n=3),PDI为0.228,电位为(-11.46±0.74)mV(n=3);包 封率为95.13%,载药量为9.04%;透射电镜照片显示纳米粒大小均一,呈球形或类球形。 结论 该处方可用于香叶木素固体脂 质纳米粒的制备,工艺简单,稳定可行。     

Hydrophilic coating of mitotane-loaded lipid nanoparticles: Preliminary studies for mucosal adhesion

The aim of the present work was to load mitotane, an effective drug for adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The SLN and NLC were successfully prepared by high shear homogenization followed by hot high pressure homogenization. Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas for NLC PEGylated stearic acid was selected as solid lipid and medium chain triacylglycerols as the liquid lipid. Tween® 80 and Span® 85 were used as surfactants for all formulations. The particle size, zeta potential, polydispersity index (PI), encapsulation efficiency (EE), and loading capacity (LC) were evaluated. The SLN showed a mean particle size of 150?nm, PI of 0.20, and surface charge ?10 mV, and the EE and LC could reach up to 92.26% and 0.92%, respectively. The NLC were obtained with a mean particle size of 250?nm, PI of 0.30, zeta potential ?15 mV and 84.50% EE, and 0.84% LC, respectively. Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective in changing zeta potential from negative to positive values. The results suggest that mitotane was efficiently loaded in SLN and in NLC, being potential delivery systems for improving mitotane LC and controlled drug release.