微通道内载紫杉醇固体脂质纳米粒制备及工艺优化

目的:制备载紫杉醇固体脂质纳米粒。方法:微通道内采用溶剂扩散法制备脂质纳米粒,并通过正交优化制备工艺。结果:制备的纳米粒稳定性良好,平均粒径为(129.87±2.91)nm,包封率为(3.11±0.06)%,载药率为(43.67±0.24)%。结论:本研究制备的载药固体脂质纳米粒载药特性与重复性良好。     

可生物降解聚乳酸纳米粒的制备及表征

采用乳化 -溶剂蒸发法 ( O/W)制备聚乳酸 ( PLA)纳米粒 ,用透射电子显微镜和激光粒度仪对纳米粒进行了表征 ,纳米粒具有规整的球形且正态分布 ,同时从有机相和水相的体积比、聚合物的浓度、表面活性剂的选择及表面活性剂的浓度等几个因素对纳米粒粒径大小的影响作了较详细地讨论。有机相与水相的体积比从 1∶ 3减小到 1∶ 30 ,纳米粒的粒径从 ( 30 6.2 + 1 1 ) nm减小到( 1 87.1 + 2 .4) nm;聚合物在有机相的浓度从 1 %(质量分数 )增加到 5 %(质量分数 ) ,纳米粒的粒径从 1 94nm增加到 32 1 nm;随着水相中表面活性剂浓度从 0 .5 (质量体积分数 )增大到 3.5 %(质量体积分数 ) ,纳米粒粒径从 2 0 2 nm减小 1 78nm且有一个低的多分散指数。而且还比较了搅拌蒸发法和减压抽提法对纳米粒表面形态的影响     

环孢素A固体脂质纳米粒制备工艺优化

为了制备单分散性优良、形态规整且具有较高包封率的环孢素A固体脂质纳米粒,采用溶剂扩散法制备环孢素A固体脂质纳米粒。在水相中加入海藻酸钠以改善纳米粒形态和单分散性,利用Ca2+与载药纳米粒胶体溶液中海藻酸钠发生配位反应形成海藻酸钙凝胶,在低离心转速下分离纳米粒并简便准确测定药物包封率。在单因素实验基础上,采用响应面设计优化载药纳米粒的制备工艺条件。结果表明,影响包封率显著因素为水含量和制备温度,在海藻酸钠用量0.1132 g、用水量52.77 mL、制备温度34.55℃优化条件下,纳米粒形态呈规整棒状,单分散性好,平均粒径为181.3 nm,平均包封率达82.45%。     

固体纳米脂质微粒的制备及性能表征

采用EIP(相转变体积)转相法,以单甘酯为脂质原料,复配硬脂醇醚-25,制备了固体纳米脂质微粒(SLN)及其悬浮液,通过对乳化温度及固体纳米脂质微粒组成的研究,优化了制备条件,表征了固体纳米脂质微粒的形貌特征、粒径及Zeta电位分布,同时又研究了其离心、储存及稀释稳定性.结果表明,在乳化温度为60℃,脂质原料与乳化剂的质量比为1:1条件下制得的固体纳米脂质微粒平均粒径为169nm,粒子呈圆形,分布均一,Zeta电位为-6.18 mV,且具备良好的离心、储存及稀释稳定性.     

正交试验法优化白花丹醌固体脂质纳米粒的制备工艺

目的:制备白花丹醌固体脂质纳米粒,并采用正交试验法优化其处方工艺.方法:采用乳化-超声分散法制备白花丹醌固体脂质纳米粒,以包封率为评价指标,通过单因素试验,考察了乳化温度、超声功率、大豆卵磷脂和泊洛沙姆188的用量比例等因素对白花丹醌包封率的影响,并以正交试验优选最佳处方工艺.结果:通过单因素与正交试验优选的最佳处方工艺为脂质用量80 mg、乳化剂用量150 mg(比例为1︰5)、乳化温度60℃、超声功率300 W.按照最佳处方工艺制备3批白花丹醌固体脂质纳米粒,平均粒径为168.93 nm,平均包封率为59.74％.结论:最佳处方工艺制备的白花丹醌固体脂质纳米粒具有较好的包封率,工艺稳定可行.     

T型微通道装置制备尺寸均一壳聚糖微球

采用T型微通道装置制备尺寸均一的壳聚糖微球. 研究了乳化剂用量、油水两相流速比和流速等条件对乳液粒径的影响,尝试制备了不同分子量的壳聚糖乳液,并确定了交联固化方式. T型微通道装置的油相通道直径350 mm,水相通道直径65 mm,两通道接口处直径16 mm. 以1.5%(w)的壳聚糖醋酸水溶液为水相,以液体石蜡/石油醚(7/5, j)的混合物作为油相,水相流速20 mL/min,油水两相流速比为15:1,4%(w)的PO-500作为油相乳化剂,制备得到的壳聚糖乳液粒径分布系数<10%. 以戊二醛的甲苯溶液作为交联剂,当戊二醛所含醛基与壳聚糖所含氨基的摩尔比为1:1时,交联时间选择2 h.     

微通道内PCL-PEG-PCL载姜黄素纳米粒的制备及体外释药评价

目的:制备姜黄素载药纳米粒。方法:开环聚合法制备PCL-PEG-PCL三嵌段聚合物,微通道界面沉淀法制备姜黄素载药纳米粒,透射电镜观察纳米粒子形貌特征,动态光散射(DLS)测定粒径及其分布,HPLC测定纳米粒子的包封率和载药量,同时考察其体外释药性能。结论:姜黄素纳米粒平均粒径200 nm左右,粒径分布较窄,平均包封率(92.76±0.58)%,载药量(10.76±1.17)%,TEM观察纳米粒呈规则球形,10 d体外累积释药量76%。     

聚哌嗪酰胺-SiO_2/聚砜中空纤维纳滤膜的制备及表征

以聚砜(PSf)为基膜,哌嗪(PIP)为水相单体、均苯三甲酰氯(TMC)为油相单体,采用界面聚合的方法制备了聚哌嗪酰胺-SiO_2/PSf中空纤维纳滤膜,通过在水相或者油相中添加SiO_2纳米粒子,使膜在维持较高截留率的情况下提高膜通量,讨论了界面聚合时间、SiO_2在水相或油相中的含量对膜性能的影响。结果表明,当水相PIP的质量浓度为10 g/L、SiO_2、PIP的质量比为0.05,油相TMC的质量浓度为1.5 g/L、界面聚合时间10 s,并在60℃下热处理15 min时,所得纳滤膜具有良好的分离性能,对于无机盐的截留率大小为Na_2SO_4MgSO_4NaClMgCl_2,表明纳滤膜表面带负电;对活性艳蓝溶液的截留率可达90%以上。     

HCFC-141b制冷剂气体水合物生长过程的形态

通过实验观测了HCFC - 141b制冷剂气体水合物的生成过程 ,认为水相和制冷剂相在过冷的条件下在界面上局部成核 ,成核扩展至两相接触的整个界面 ,水合物的进一步生成是由于制冷剂相通过水合物层扩散到水相中形成的 .利用显微实验的生成图像计算了水合物晶体的生长速率 ,并与外冷实验中的晶体生长速率比较 ,认为扰动增大了制冷剂相和水相的两相相界面的接触维数 .     

不同T型微通道内弹状流相分离规律的实验研究

为获得不同形式顺流T型、冲击T型跨尺度通道对两相流流型的不同调控作用,设计跨尺度-并行多T型管-单晶硅方形通道,增大分液量的同时获得更接近实际应用的多分支口最长气弹伸缩长度;利用高速压力监测系统及高速摄像监测系统分别监测T型分支通道的压力及两相流界面运动,获得不同形式微通道相分离弹状流的压力波动及分液规律,建立微通道内气液界面运动与宏观调控参数两相流流速、压差之间的相关性,同时证明冲击型跨尺度微通道具有更高分液能力。     

Formation of solid lipid nanoparticles in a microchannel system with a cross-shaped junction

This work presents a novel method for generating solid lipid nanoparticles (SLNs) in a microchannel system with a cross-shaped junction formed by a main microchannel and two branches. A lipid solution by dissolving the lipid in a water-miscible organic solvent was passed through the main channel, while an aqueous surfactant solution was introduced into the branches simultaneously. These two liquids met together at the cross-shaped junction and passed along the main channel. The solvent diffused from the lipid solution stream into the aqueous phase, which resulted in the local supersaturation of lipid and thus led to the formation of SLNs. The flow behaviors of lipid and aqueous phase zones were measured by a digital inversion microscope system. The mean particle diameter and the particle size distribution of the obtained SLNs were measured by dynamic light scattering (DLS) method and the particle morphology was examined by transmission electron microscopy (TEM). The effects of liquid flow velocity and lipid concentration on the properties of SLNs were investigated experimentally. The formation mechanism of SLNs in the present microchannel system was discussed and analyzed.     

Bubble splitting under gas–liquid–liquid three‐phase flow in a double T‐junction microchannel

Gas–aqueous liquid–oil three‐phase flow was generated in a microchannel with a double T‐junction. Under the squeezing of the dispersed aqueous phase at the second T‐junction (T2), the splitting of bubbles generated from the first T‐junction (T1) was investigated. During the bubble splitting process, the upstream gas–oil two‐phase flow and the aqueous phase flow at T2 fluctuate in opposite phases, resulting in either independent or synchronous relationship between the instantaneous downstream and upstream bubble velocities depending on the operating conditions. Compared with two‐phase flow, the modified capillary number and the ratio of the upstream velocity to the aqueous phase velocity were introduced to predict the bubble breakup time. The critical bubble breakup length and size laws of daughter bubbles/slugs were thereby proposed. These results provide an important guideline for designing microchannel structures for a precise manipulation of gas–liquid–liquid three‐phase flow which finds potential applications among others in chemical synthesis. © 2017 American Institute of Chemical Engineers AIChE J, 63: 376–388, 2018     

Continuous production of solid lipid nanoparticles by liquid flow-focusing and gas displacing method in microchannels

The liquid flow-focusing and gas displacing method is developed to produce solid lipid nanoparticles (SLNs) continuously in a microchannel, which has a cross-junction for the focus of lipid and aqueous solutions and a T-junction for the injection of gas bubbles. The liquid flow-focusing was achieved by introducing a lipid solution with a water-miscible organic solvent and an aqueous surfactant solution simultaneously through the two branches of the cross-junction into the main channel, while the gas displacing was accomplished by injecting an inert gas (N₂) through the T-junction at the downstream of the cross-junction into the main flow streams upward to form gas-liquid slug flow. Solid lipid nanoparticles were formed due to the local supersaturation of lipid induced by the diffusion of the solvent from the lipid solution stream into the aqueous phase. The liquid suspension containing solid lipid nanoparticles then passed freely through the microchannel without any blockage by the contribution of gas slug flow. The flow behaviors were observed by a digital inversion microscope system and the hydrodynamics of the liquid flow-focusing streams and the gas slug flow were investigated. Particle size distributions of the solid lipid nanoparticles obtained under various conditions were measured by dynamic light scattering and the particle morphology was examined by transmission electron microscopy. The influences of liquid velocity and lipid concentration under the gas displacing condition on the properties of solid lipid nanoparticles were studied experimentally. The solid lipid nanoparticles with small size (the mean size in the range of 120-200 nm) and narrow particle size distribution (with values of polydispersity index in the range of 0.14-0.19) had been produced by this method. The crucial roles of Taylor bubbles and liquid slugs in the formation of solid lipid nanoparticles were considered and the transfer mechanism of slug flow on the formation and passage of solid lipid nanoparticles in the microchannel were also discussed. Compared with other production methods for SLNs (e.g., hot homogenization, warm microemulsions and supercritical fluid technique), the proposed method in this work is simple and no overcritical operations are needed during the preparing process. Therefore, it can be employed to prepare SLNs with small sizes and a narrow diameter distribution.     

Preparation and Characterization of Catalase-Loaded Solid Lipid Nanoparticles Protecting Enzyme against Proteolysis

Catalase-loaded solid lipid nanoparticles (SLNs) were prepared by the double emulsion method (w/o/w) and solvent evaporation techniques, using acetone/methylene chloride (1:1) as an organic solvent, lecithin and triglyceride as oil phase and Poloxmer 188 as a surfactant. The optimized SLN was prepared by lecithin: triglyceride ratio (5%), 20-second + 30-second sonication, and 2% Poloxmer 188. The mean particle size of SLN was 296.0 ± 7.0 nm, polydispersity index range and zeta potential were 0.322-0.354 and -36.4 ± 0.6, respectively, and the encapsulation efficiency reached its maximum of 77.9 ± 1.56. Catalase distributed between the solid lipid and inner aqueous phase and gradually released from Poloxmer coated SLNs up to 20% within 20 h. Catalase-loaded SLN remained at 30% of H(2)O(2)-degrading activity after being incubated with Proteinase K for 24 h, while free catalase lost activity within 1 h.     

微通道中钒的液-液流型和萃取传质动力学研究

采用伯胺N1923萃取剂在微通道中研究V(V)的液-液流型和萃取传质动力学,以15vol% N1923作为连续相、钒氧酸根水溶液作为分散相,研究不同流速下两不混溶相的流型变化规律及两相停留时间和微通道管径作为流速的函数对传质的影响。随两相流速增大,段塞流长度和比界面面积基本不变,且两相流体由Raydrop微通道流入外接毛细管微通道时由于微通道的扩张会改变两相流动方式,使同一实验条件下在微通道中同时出现多种流型,与此同时两相流速和总体积传质系数(kLa)呈正相关,表明流型在本研究体系中对传质的影响可忽略。在相同管径通道内,停留时间与总体积传质系数呈负相关,表明在两相接触通道入口处发生了显著传质。在相同的两相混合速度和相比下,254 μm的管径传质效果是750 μm的9倍,表明小管径内传质效果更加,循环强度更大。最后将实验总体积传质系数结果与总体积传质系数的经验式进行了关联,有望为实现将微通道放大的绿色冶金技术提供理论基础。     

正弦型微通道内液-液两相流型及流动特性实验研究

采用实验的方法对不混溶的液液两相流体在不同入口结构下的正弦微通道(直通道正弦、波峰正弦和波中正弦)内液滴的流动特性进行了分析。硅油作为离散相,含有0.5% SDS的蒸馏水作为连续相,观测到弹状流、滴状流和射状流。分析了两相流动参数及不同的微通道入口结构对流型和液滴长度的影响。流型受微通道入口结构影响较大,波峰正弦微通道能够生成最大范围的稳定的流型。液滴长度随离散相体积流量和离散相与连续相体积流量之比的增大而增大,随连续相的体积流量和毛细数的增大而降低。微通道入口结构对液滴长度有影响,直通道的正弦微通道内液滴长度最短,更有利于液滴的形成。三种通道生成的液滴中,最大的液滴尺寸是最小的液滴尺寸的1.15~1.39倍,但正弦流动段对液滴速度几乎没有影响。     

单分散性PLGA磁性微球制备及其缓释性研究

为获得单分散性PLGA磁性微球,文中以纳米四氧化三铁明胶分散液作为内水相(W1),PLGA（聚乳酸羟基乙酸共聚物）的二氯甲烷溶液作为油相(O),PVA（聚乙烯醇）水溶液作为外水相(W2),利用T型微通道并采用复合乳液法制备PLGA磁性微球,考察流速比和油相与内水相体积比对微球制备的影响。借助FTIR、SEM及VSM（振动样品磁强计）对磁性微球组分、形貌、粒径分布和磁学性能进行表征;并以阿司匹林作为药物模型进行缓释性测试。结果表明：流速比v(W2):v(W1/O)=120:1且体积比V(O):V(W1)=2:1时可均匀成球,其粒径分布系数CV值仅为4.66%,表现出良好单分散性;此时比饱和磁化强度可达1.52emu/g,兼具优异顺磁性。制得的载药微球在60h内表现出阶段性匀速释放,且有较好磁响应性,有望用于磁响应性药物载体。     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres featuring monodispersity and controllable particle size using a microchannel device

Poly(lactic‐co‐glycolic acid) (PLGA) microspheres prepared using a traditional solvent evaporation or double emulsification method are usually polydisperse with an uncontrollable particle size distribution, which brings about poor application performance. In our research, monodisperse magnetic PLGA microspheres were prepared using a microchannel device based on a water‐in‐oil‐in‐water composite emulsion. The composite emulsion was formed by injecting a dichloromethane–gelatin water‐in‐oil emulsion into a microchannel together with an external water phase, i.e. poly(vinyl alcohol) (PVA) aqueous solution. Mean particle size control of the microspheres was executed using the osmotic pressure difference between internal and external aqueous phases caused by regulating NaCl concentration in PVA aqueous phase. It is found that monodisperse magnetic PLGA microspheres with high magnetic responsiveness can be successfully prepared combining the microchannel device with composite emulsion method. Mean particle size of the microspheres with coefficient of variation value below 4.72% is controllable from 123 to 203 µm depending on the osmotic pressure. The resulting samples have pyknotic and smooth surfaces, as well as spherical appearance. These monodisperse magnetic PLGA microspheres with good superparamagnetism and magnetic mobility have potential use as drug carriers for uniform release and magnetic targeting hyperthermia in biological fields. © 2015 Society of Chemical Industry     

T形微通道中互不相溶两相流数值模拟

采用摄动有限体积（PFV）算法和水平集（level set）技术对T形微通道内互不相溶两相流动进行了数值模拟研究。考察了两相界面张力和微通道壁面润湿性对流动的影响,精确地捕捉到了油水两相流动的界面。对一些典型的T形微通道油水两相流动进行了数值计算,模拟结果和实验结果吻合较好。分析总结出了微通道内两相流动过程中的一些基本规律,为微通道内的液液两相流动实验设计和工业应用提供了新的数值预测手段。