正交优化聚乳酸-羟基乙酸纳米粒的制备

背景:聚乳酸-羟基乙酸纳米粒或纳米微球用于制备生物降解型缓释或定向给药体系已经研究了近30年,是国内外研究的热点。该体系能够控制粒径大小、延缓药物降解、延长药物释放时间、靶向释放、降低药物毒性和刺激性等。目的:以紫杉醇为模型药物、聚乳酸-羟基乙酸为包裹材料,探索载药纳米粒的制备条件对粒径、包封率等的影响,确定最佳制备工艺条件。方法:采用乳化-溶剂挥发法制备聚乳酸-羟基乙酸纳米粒,以粒径、包封率和载药量等为观察指标,通过正交设计法优化纳米粒制备工艺条件。结果与结论:通过正交实验设计,优化了制备工艺条件,其最佳条件是超声乳化时间为15min,乳化剂浓度为1%,油水相比为1∶25,合成温度为25℃。在此条件下进行实验,制备出的载药纳米粒粒径为217.6nm,载药量1.79%,包封率85%。该制备工艺简单、稳定,优化制备条件,可制备出包封率高、粒径适宜的紫杉醇-聚乳酸-羟基乙酸纳米粒。     

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     

美斯地浓聚乳酸载药纳米粒的制备及体外释放

背景：美斯地浓临床常用于治疗重症肌无力,但其水溶性较强,半衰期短,生物利用度低,给药频率高,患者依从性差,因此提高其缓释作用对临床应用有重要意义。 目的：制备美斯地浓聚乳酸纳米粒,并考察其体外释放性能。 方法：以聚乳酸为载药材料,采用复乳液中干燥法制备美斯地浓聚乳酸纳米粒,运用单因素实验设计优化处方,动态透析法进行体外药物释放实验。 结果与结论：确定以二氯甲烷作为油相制备纳米粒,内水相与油相的比例1∶10,聚乳酸浓度6%,外水相聚乙烯醇浓度3%,美斯地浓投药量40 mg为最佳制备工艺,此条件制备的药物纳米粒包封率和载药率分别为(67.59±1.46)%和(4.31±0.17)%。美斯地浓聚乳酸纳米粒的平均粒径为937 nm,圆球形,表面光滑,未观察到粘连现象。与美斯地浓游离药物相比,美斯地浓聚乳酸纳米粒存在突释现象,之后呈现缓慢释放特性,72 h释放量为57.03%,提示成功制备美斯地浓聚乳酸纳米粒,具有缓释效应。     

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。     

左旋多巴和姜黄素共递送protocells纳米粒的制备及体外评价

目的制备共载左旋多巴和姜黄素protocells纳米粒并进行体外评价。方法以介孔二氧化硅为内核,脂质双分子层为外膜,制备共载左旋多巴和姜黄素protocells纳米粒。使用激光粒度分析仪和透射电子显微镜对所制备纳米粒的形貌、粒径、多分散系数(PDI)和Zeta电势进行表征;采用高效液相色谱法对所制备纳米粒的载药量和包封率进行测定;采用透析袋法对所制备纳米粒的体外释放特性进行考察;应用粒径、Zeta电势、载药量等指标对所制备纳米粒的室温贮存稳定性进行评价。结果制备的载左旋多巴和姜黄素protocells纳米粒粒径分布均一性好、粒子表面呈电负性、平均粒径为(210.9±2.8)nm、PDI为(0.201±0.011)。其中左旋多巴的载药量为(20.28±0.43)%、包封率为(10.14±0.22)%;姜黄素的载药量为(1.97±0.01)%、包封率为(98.32±0.01)%。体外释放结果表明该纳米粒48 h姜黄素累计释放率为59.2%,且可有效阻止左旋多巴的泄漏,降低其在循环系统中的暴露量。稳定性结果表明左旋多巴和姜黄素在protocells纳米粒中稳定性良好。结论载左旋多巴和姜黄素的protocells纳米粒制备工艺简单,具有良好的理化性质、稳定性及所预期的释放性能。     

盐酸表阿霉素纳米靶向制剂的缓释效应

背景：盐酸表阿霉素是一种广谱抗生素,目前临床使用的不足多为药物释放快、目标组织药物浓度低,静脉给药后广泛分布于体内各种组织器官,不良反应明显。 目的：针对盐酸表阿霉素临床应用的不足,制备盐酸表阿霉素纳米靶向注射制剂。 方法：以叶酸偶联牛血清白蛋白为载体,采用乳化-高压匀质法,制备盐酸表阿霉素纳米靶向注射制剂,以激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及Zeta电位,扫描电镜观察纳米颗粒的表面形态,高效液相色谱法分析白蛋白负载盐酸表阿霉素纳米制剂的包封率、载药量和释药性能。 结果与结论：制备的盐酸表阿霉素纳米粒外观呈均匀球型,粒径分布较窄,平均粒径为(157.73±     0.40) nm,平均 Zeta 电位为(-30.85±0.43) mV,载药量 22.78%,包封率可达96.24%。体外模拟释药结果表明药物释放曲线分为两个阶段,突释阶段微球释药量在24 h内达42.6%,缓释阶段纳米粒释药持续时间长,在112 h 时释药量达 84.1%,载药纳米粒的药物释放速率持续稳定。结果表明乳化结合高压匀质法制备的盐酸表阿霉素纳米靶向制剂粒径均匀,粒径范围分布窄,载药量和包封率高,具有一定的缓释作用。     

载牛血清蛋白的PLGA纳米粒制备工艺的优化及特性研究

目的制备载牛血清蛋白(BSA)的PLGA纳米粒(NPs),采用正交试验设计对工艺进行优化筛选,并研究其特性。方法以聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]为载体,二氯甲烷(DCM)和丙酮为有机溶剂,采用复乳化溶剂挥发法制备载BSA的PLGA载药纳米粒。扫描电镜观察纳米粒形态,纳米粒度分析仪测定平均粒径和粒径分布;BCA法测定纳米粒的包封率;同时考察其体外释放特性。结果优化条件下制备的纳米粒呈大小均匀的球形粒子,平均粒径为219nm,包封率为44.7%;体外释放分初期突释和后期缓释两阶段,其2～28d的释放曲线符合Higuchi方程,28d末的累积释放量为87.37%。结论以PLGA为载体的BSA纳米粒具有较小的粒径、较高包封率和明显的缓释性能。     

姜黄素/聚(α-氰基丙烯酸异丁酯)载药微球的制备及其药物释放

以α-氰基丙烯酸异丁酯(iBCA)为原料、泊洛沙姆188为乳化剂,以捏合法制得的姜黄素(Cur)/羟丙基-β-环糊精(HP-β-CD)包合物(Cur-HP-β-CD)为负载药物,经一步乳化法制得姜黄素/聚(α-氰基丙烯酸异丁酯)载药微球(Cur-HP-β-CD-PiBCA)。考察乳化剂、负载药物的浓度对微球粒径与分布、微球载药率及包封率的影响,并对载药微球的药物释放进行了研究。结果表明:随着乳化剂浓度从0.01%增加到0.07%,载药微球粒径下降,粒径分布变宽,载药率和包封率均增加,适宜的乳化剂浓度为0.05%;随着药物浓度从0.03%增加到0.07%,微球载药率升高,包封率下降;载药微球的载药率越高,最终的药物累积释放百分率越低。姜黄素经包合和负载,不仅可以有效改善其亲水性,而且可以提高其溶出度,为提高姜黄素的生物利用度奠定了基础。     

聚乳酸-羟基乙酸纳米粒的制备*

背景：聚乳酸-羟基乙酸是一种生物相容性良好的可降解材料,确定其最佳制备工艺条件,有利于聚乳酸-羟基乙酸后续药物载体研究与工业化生产条件的确立。 目的：以聚乳酸-羟基乙酸为包裹材料,探索纳米粒的制备条件对粒径、表面形态等的影响,确定最佳制备工艺条件。 方法：采用乳化-溶剂挥发法制备聚乳酸-羟基乙酸纳米粒,以粒径为观察指标,探讨乳化剂种类、乳化剂含量、油相种类、超声时间、挥发时间、油相与水相体积比(W∶O)以及聚合物质量浓度等制备条件对纳米粒粒径的影响,确定制备聚乳酸-羟基乙酸纳米粒的最佳工艺条件。 结果与结论：优化后的制备工艺条件是在室温下,以一定的搅拌速度和滴加速度,选择常用无毒的乳化剂,浓度在0.3%~1.0%,丙酮为有机相,超声时间8~15 min、挥发时间6~10 h、水油相比(W∶O)>25∶1,聚合物质量浓度<60 g/L。提示该制备工艺简单、稳定,优化制备条件,可制备出表面形态规整、粒径适宜的聚乳酸-羟基乙酸纳米粒。     

Poly(lactide)–vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel

Four systems of nanoparticles of biodegradable polymers were developed in this research for oral delivery of anticancer drugs with Docetaxel used as a model drug, which include the poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), the poly(lactide)–vitamin E TPGS nanoparticles (PLA–TPGS NPs), the poly(lactic-co-glycolic acid)–montmorillonite nanoparticles (PLGA/MMT NPs) and the poly(lactide)–vitamin E TPGS/montmorillonite nanoparticles (PLA–TPGS/MMT NPs). Vitamin E TPGS stands for d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), which is a water-soluble derivative of natural vitamin E formed by esterification of vitamin E succinate with polyethylene glycol (PEG) 1000. The design was made to take advantages of TPGS in nanoparticle technology such as high emulsification effects and high drug encapsulation efficiency, and those in drug formulation such as high cellular adhesion and adsorption. MMT of similar effects is also a detoxifier, which may cure some side effects caused by the formulated drug. The drug-loaded NPs were prepared by a modified solvent extraction/evaporation method and then characterized for their MMT content, size and size distribution, surface charge and morphology, physical status and encapsulation efficiency of the drug in the NPs, and in vitro drug release profile. Cellular uptake of the coumarin 6-loaded NPs was investigated. In vitro cancer cell viability experiment showed that judged by IC₅₀, the PLA–TPGS/MMT NP formulation was found 2.89, 3.98, 2.12-fold more effective and the PLA–TPGS NP formulation could be 1.774, 2.58, 1.58-fold more effective than the Taxotere^® after 24, 48, 72 h treatment, respectively. In vivo PK experiment with SD rats showed that oral administration of the PLA–TPGS/MMT NP formulation and the PLA–TPGS NP formulation could achieve 26.4 and 20.6 times longer half-life respectively than i.v. administration of Taxotere^® at the same 10 mg/kg dose. One dose oral administration of the NP formulations could realize almost 3 week sustained chemotherapy in comparison of 22 h of i.v. administration of Taxotere^®. The oral bioavailability can be enhanced from 3.59% for Taxotere^® to 78% for the PLA–TPGS/MMT NP formulation and 91% for the PLA–TPGS NP formulation respectively. Oral chemotherapy by nanoparticles of biodegradable polymers is feasible.     

The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles

Paclitaxel is one of the most effective antineoplastic drugs. Its current clinical administration is formulated in Cremophor EL, which causes serious side effects. Nanoparticle (NP) technology may provide a solution for such poisonous adjuvant problems and promote a sustained chemotherapy, in which biodegradable polymers play a key role. Our group has successfully synthesized novel poly(lactide)-tocopheryl polyethylene glycol succinate (TPGS) (PLA-TPGS) copolymers of desired hydrophobic-hydrophilic balance for NP formulation of anticancer drugs. The present work is focused on effects of the PLA:TPGS composition ratio on drug encapsulation efficiency, in vitro drug release, in vitro cellular uptake and viability of the PLA-TPGS NP formulation of paclitaxel. The PLA-TPGS copolymers of various PLA:TPGS ratios were synthesized by the ring-opening polymerization method and characterized by GPC and (1)H NMR for their molecular structure. Paclitaxel-loaded PLA-TPGS NPs were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy for surface morphology and zeta potential for surface charge. High performance liquid chromatography was used to measure the drug encapsulation efficiency and in vitro drug release profile. Cancer cell lines HT-29 and Caco-2 were used to image and measure the cellular uptake of fluorescent PLA-TPGS NPs. Cancer cell viability of the drug-loaded PLA-TPGS was measured by MTT assay. It was found that the PLA:TPGS composition ratio has little effects on the particle size and size distribution. However, the PLA-TPGS NPs of 89:11 PLA:TPGS ratio achieved the best effects on the drug encapsulation efficiency, the cellular uptake and the cancer cell mortality of the drug-loaded PLA-TPGS NPs. This research was also carried out in close comparison with the drug-loaded PLGA NPs.     

Nanoparticles of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers for protein drug delivery

Nanoparticles (NPs) of poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS) copolymers with various PLA:TPGS component ratios were prepared by the double emulsion technique for protein drug formulation with bovine serum albumin (BSA) as a model protein. Influence of the PLA:TPGS component ratio and the BSA loading level on the drug encapsulation efficiency (EE) and in vitro drug release behavior was investigated. The PLA-TPGS NPs achieved 16.7% protein drug loading and 75.6% EE, which exhibited a biphasic pattern of controlled protein release with higher initial burst for those NPs of more TPGS content. Furthermore, the released proteins retained good structural integrity for at least 35 days at 37 degrees C as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism (CD) spectroscopy. Compared with other biodegradable polymeric NPs such as poly(D,L-lactide-co-glycolide) (PLGA) NPs, PLA-TPGS NPs could provide the encapsulated proteins a milder environment. Confocal laser scanning microscopy (CLSM) observation demonstrated the intracellular uptake of the PLA-TPGS NPs by NIH-3T3 fibroblast cells and Caco-2 cancer cells. This research suggests that PLA-TPGS NPs could be of great potential for clinical formulation of proteins and peptides.     

In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D,L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation

This work shows a full spectrum of research on Vitamin E TPGS-emulsified Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for paclitaxel formulation to improve its therapeutic index and to reduce the adverse effects of adjuvant Cremophor EL in its current clinical formulation of Taxol. Paclitaxel-loaded PLGA NPs were prepared by a modified solvent extraction/evaporation technique with vitamin E TPGS as emulsifier. The formulated NPs were found in quite uniform size of approximately 240 nm diameter. The in vitro drug release profile exhibited a biphasic pattern with an initial burst followed by a sustained release. In vitro HT-29 cell viability experiment demonstrated that the drug formulated in the NPs was 5.64, 5.36, 2.68, and 1.45 times more effective than that formulated in the Taxol formulation after 24, 48, 72, 96 h treatment, respectively at 0.25 microg/mL drug concentration, which should be even better with the sustainable release feature of the NPs formulation considered. In vivo PK measurement confirmed the advantages of the NP formulation versus Taxol. The area-under-the-curve (AUC) for 48 h for Vitamin E TPGS emulsified PLGA NP formulation of paclitaxel were found 3.0 times larger than that for the Taxol formulation. The sustainable therapeutic time, at which the drug concentration drops below the minimum effective value, for the NP formulation could be 1.67 times longer than that for the Taxol formulation.     

Fabrication and statistical optimization of surface engineered PLGA nanoparticles for naso-brain delivery of ropinirole hydrochloride: in-vitro–ex-vivo studies

Ropinirole hydrochloride (RPN), a nonergot dopamine D₂-agonist used in the management of Parkinson’s disease, has poor oral bioavailability (52%) due to extensive hepatic metabolism. The intent of present research work was aimed at design and statistical optimization of RPN-loaded poly (lactic-co-glycolic acid) (PLGA)-based biodegradable nanoparticles (NPs) surface modified using natural emulsifier, vitamin E (d-α-tocopheryl polyethylene glycol 1000 succinate [TPGS]) for direct nose-to-brain delivery in order to avoid hepatic first-pass metabolism, and improve therapeutic efficacy with sustained drug release. RPN-NPs were prepared by modified nanoprecipitation technique and optimized using 2³ factorial design of experiment. The effect of polymer and emulsifier concentration was evaluated on particle size and entrapment efficiency (EE%). Formulation PL₆ was considered as desirable with highest EE% (72.3?±?6.1%), PS (279.4?±?1.8?nm), zeta potential (?29.4?±?2.6?mV), and cumulative drug diffusion of 96.43?±?3.1% in 24?h. The ANOVA results for the dependent variables demonstrated that the model was significant (p value?<?0.05) for response variables. Histopathological study of optimized batch (PL₆) demonstrated good retention of NPs with no severe signs of damage on the integrity of nasal mucosa. Differential scanning calorimetry revealed the absence of any chemical interaction between RPN, PLGA, and TPGS while SEM study confirmed spherical shape of optimized NPs. Accelerated stability studies of freeze-dried optimized batch demonstrated negligible change in the average PS and EE% after storage at 25?±?2?°C/60?±?5% (relative humidity (RH) for the period of three months. The promising results of optimized batch suggested practicability of investigated system for enhancement of bioavailability and brain targeting of CNS acting drugs like RPN.     

聚乳酸载药纳米微粒的表面修饰及体外评价

本研究的目的是用O 羧甲基壳聚糖作乳化剂和表面修饰剂 ,采用超声乳化法制备聚乳酸载药纳米微粒 ,并对聚乳酸载药纳米微粒进行表面修饰 ,然后分别对载药纳米微粒的表面形貌、粒径分布、微粒结构、表面元素、体外释放和肿瘤细胞抑制率等微粒性能进行考察与评价。实验证明 ,O 羧甲基壳聚糖可用于制备纳米药物载体系统 ,对聚乳酸载药纳米微粒的制备起到很好的乳化性能和表面修饰作用。采用复乳法制备包载 5 Fu的PLA/O CMC纳米微粒的平均粒径在 5 0nm ,在PBS缓冲溶液中释放时间可达 12d。在对胃癌、乳腺癌和大肠癌三种肿瘤细胞的抑制率测定实验中 ,PLA/O CMC纳米微粒的肿瘤细胞抑制率分别可以达到 72 .8%、77.3%和 75 .6 % ,接近或等同于游离 5 Fu药物的抑制率。在作用时间上 ,PLA/O CMC载药纳米微粒也显示出良好的缓释效应。     

Potential use of cholecalciferol polyethylene glycol succinate as a novel pharmaceutical additive

D-alpha-tocopheryl polyethylene glycol succinate (TPGS) has been utilized in numerous drug delivery formulations in recent years. Because of its amphiphilic structure, it can be used as emulsifier and vehicle for lipid-based drug delivery formulations. It is also an effective P-glycoprotein (P-gp) inhibitor. However, TPGS represents only one of the surfactants in the class of "Vitamin-PEG" conjugated surfactants. To design a new adjuvant or additive, a conjugate made of vitamin D (cholecalciferol) and PEG-cholecalciferol polyethylene glycol succinate (CPGS) was synthesized via a two-step reaction. We hypothesized that CPGS may exhibit similar characteristics to TPGS, and thus the physicochemical properties as well as the anticancer properties of CPGS were studied. The results demonstrated that CPGS reduced the particle size and increased the encapsulation efficiency of the PLGA nanoparticles, indicating that CPGS may also have the emulsifier function similar to TPGS. The drug release profiles showed that the nanoparticles with CPGS additive had a lower initial burst and more sustained release pattern. In vitro testing with Caco-2 cells showed that CPGS could increase the cytotoxicity of DOX-loaded PLGA nanoparticles. Based on the rhodamine accumulation study, the increased cytotoxicity is possibly due to the P-gp inhibition by CPGS. From current results, the use of CPGS as an adjuvant is promising and may enhance the efficacy of the overall drug delivery system.     

反相微乳液法制备麦醇蛋白纳米颗粒的初步研究

目的 常规去溶剂法制备的麦醇蛋白颗粒因粒径偏大（400 ～ 500 nm）易被网状内皮系统捕获。采用反相微乳液法制备粒径 〈 100 nm的麦醇蛋白纳米颗粒。方法 用反相微乳法,以液体石蜡为油相,二硫苏糖醇（DTT）还原的麦醇蛋白乙醇溶液为水相,Tween80-Span80为复合乳化剂。按质量比1/7 ~ 1/3称取Tween80和Span80,按质量比1/6 ~ 1/2与石蜡混合均匀,配制复合乳化剂和油相的混合溶液。在水相液滴中,麦醇蛋白被加入的H2O2氧化形成二硫键而交联固化,形成纳米颗粒。结果 乳液制备工艺与复合乳化剂配比、复合乳化剂与油相质量比、搅拌速度有关,得到最佳制备工艺为：以液体石蜡为油相,5.0 mg/mL麦醇蛋白乙醇/水（70 %,v/v）溶液为水相,Tween80-Span80（1/7,w/w）为复合乳化剂,乙醇为助乳化剂,水相/油相比例 2/30（v/w）,复合乳化剂/油相比例 1/3（w/w） ,搅拌速度1 000 r/min。得到麦醇蛋白纳米颗粒粒径为20 ～ 100 nm,颗粒中不含DTT、复合乳化剂和H2O2,纳米颗粒的热稳定性优于麦醇蛋白原料,并且纳米颗粒无细胞毒性,且细胞毒性评级均为0级。结论 用反相微乳法可以获得用作为药物载体的麦醇蛋白纳米颗粒。 更多     

Preparation and Evaluation in Vitro of BCNU-Loaded PLA Nanoparticles

In this study, using a spontaneous emulsification/solvent extraction method, BCNU-Ioaded PLA nanoparticles (NPs) with small particle size and narrow size distribution have been acquired. The particle size of the NPs ranged from 40-60 nm and 100-200 nm according to different requirements. SEM and TEM showed that the particle size considerably decreases with increasing emulsification concentration and decreasing PLA concentration and ratio of oil to water. The highest drug loading ratio and drug encapsulation efficiency of NPs were 5. 63% and 33.45%. The results demonstrated that decrease of initial BCNU content resuited in a noticeably increased encapsulation yield. A thorough study in vitro showed that the drug could be steadily released from NPs for one week. In addition, drug-loaded NPs had higher antitumor activity, compared with free BCNU,and sustained drug release characteristics as well.