《材料化学实验》案例之聚乳酸载药微球的制备

聚乳酸作为一种人体可降解高分子材料,适合作为载药微胶囊载体。针对材料化学实验的需求,本论文提出一个聚乳酸载药微球的制备和性能研究实验。采用乳液法制备载药聚乳酸微球,紫外可见分光光度计测量载药率和缓释效果。微球的制备过程和结果表征开展条件简单,工艺流程难度和时间适合单个综合实验,是一个适宜的材料化学综合实验,可以作为材料大类专业的实验参考。     

聚乳酸医用缝合线载药微球附载效果测试与优化

研究了单股型聚乳酸医用缝合线的制备及对其进行载药微球附载效果测试与方案优化。采用正交试验法,设计了3个因素:溶液浓度、震荡时间、浸轧次数,每个因素设定5个水平。按照试验方案对聚乳酸缝合线进行微球附载后,测试其附载后质量增加率。结果表明:当溶液质量浓度为6 g/m L、震荡时间为10 min、浸轧次数为4次时,所制备的聚乳酸医用缝合线载药微球附载增重率最大,即附载效果最好。     

载体材料与载药微粒的释放性能：介观模拟和实验分析

选用可降解聚合物PLA,PLGA和固体脂三硬脂酸甘油酯、三嵛酸甘油酯为载体,制备包载布洛芬药物的载药微粒.通过DSC、XRD等测试分析和计算机介观模拟,从载体与药物的相容性、药物在载体中的分布状态等,探讨了载体材料对药物包封率和释放性能的影响.药物与载体的相容性好有利于药物的包封;药物均匀分布在载体中,将减缓药物的释放速率.以三硬脂酸甘油酯、三嵛酸甘油酯为载体时,药物分布在载体的外层空间,以PLA,PLGA为载体时,药物分布在载体内部,结果显示,聚合物载药微粒体外释放速率小于固体脂载药微粒.因而聚合物载药微粒更适合需要长时间缓慢释放的情况.     

固体脂质微颗粒表面稳定剂的分布状况对其稳定性的影响：介观模拟与实验

用耗散粒子动力学（DPD）方法研究了稳定剂在负载布洛芬的固体脂质微颗粒（solid lipid microparticles, SLM）表面的分布状况。模拟结果表明：以卵磷脂为稳定剂，当布洛芬的摩尔分数为1%和2%时，卵磷脂较好地包覆在颗粒的表面；而当布洛芬的摩尔分数增大到3%和5%时，卵磷脂不能覆盖在布洛芬分子密集的部位。以poloxamer 407和PVA为稳定剂，随着布洛芬摩尔分数由1%增大到5%，稳定剂都能很好地包覆在颗粒的表面。实验现象较好地吻合了模拟结果。采用DPD模拟方法，可以加深了解多相复杂载药体系的微观结构并对实验现象进行分析，为SLM稳定剂的筛选提供理论指导。     

改性聚乳酸载药微球的制备及性能

以尼莫地平为模型药物,聚乳酸(PLA)为载体材料,采用溶剂蒸发萃取法制备了N-乙烯基吡咯烷酮(NVP)接枝聚乳酸共聚物(PLA-g-PVP)微球,考察了聚乳酸质量分数、乳化剂质量分数、转速和投药质量比对微球的影响。采用红外光谱、差式扫描量热分析表征药物与载体的相互作用,扫描电镜观察微球表面形态,对不同接枝率共聚物微球的粒径、载药量、包封率及体外释放性能进行研究。结果表明,当w(PLA)=4%,w(乳化剂)=3%,转速9 000 r/min,投药质量比为2∶3时,不同接枝率改性聚乳酸微球形态圆整,平均粒径小于10μm,粒径分布窄,微球可连续释放14 d以上,释放速率随着接枝率增大而增大。     

聚乳酸微球的制备

以L-乳酸为原料,锡粒为催化剂,实现了丙交酯的开环聚合反应,红外光谱结果表明,合成了分子量可控的聚乳酸。以二氯甲烷为溶剂,聚乙烯醇为表面活性剂,制备了聚乳酸微球,研究了聚乙烯醇浓度对聚乳酸微球的影响。结果表明,当聚乙烯醇浓度增加时,微球半径变小,但粒径分布均匀度下降,聚乙烯醇浓度为1%时,聚乳酸成球效果较好。     

聚乳酸-壳聚糖共聚物载药微球的制备及性能研究

为了改善聚乳酸(PLLA)的组织相容性及细胞亲和性,提高盐酸乌拉地尔生物利用率,文中在催化剂4-(二甲胺基)吡啶与N,N'-二环己基碳酰亚胺共同作用下,将含亲水基团的碱性聚电解质壳聚糖(CS)与PLLA共聚,制备了聚乳酸-壳聚糖接枝共聚物(PLCS),采用溶剂挥发法制备盐酸乌拉地尔PLCS微球并对其结构进行了表征,同时对微球的包封率和药物释放进行了测试。通过有机相加入乙醇的方法可以提高微球对药物的包封率。结果表明,当无水乙醇与三氯甲烷的体积比为1∶2时,制得的微球包封率最高,达到34.86%。体外药物释放结果表明,PLCS微球具有明显的缓释作用,其释药动力学满足Higuchi方程。     

聚乳酸微球的制备工艺研究

以聚乳酸为基础材料,选择聚乙烯醇为乳化剂,采用O/W乳化-溶剂挥发法制备形态较好的聚乳酸微球.在可确定因素固定下来后,在保证成球质量的基础上,分别通过调节乳化剂的浓度和其它因素在一定范围内来控制微球的平均粒径.单因素实验结果表明,PLA浓度、乳化剂浓度、搅拌速度、滴加速度对微球性能影响显著.通过正交实验得出制备粒径大小为100 μm左右聚乳酸微球的最佳工艺方案为:搅拌速度600 r·min-1,PLA浓度9%(g·mL-1),PVA浓度0.5%(g·mL-1),滴加速度1.5 mL·min-1.     

聚合物载药微球活性组分控释性能的动力学模拟

将聚合物载药微球的溶解扩散模型与药代动力学模型相结合,计算了载药微球的药物控释性能的浓度时间曲线.采用叠加法计算了多次投药所产生的稳态药物浓度特征,探讨了释放速率、给药时间间隔对药物浓度曲线的影响.相对于口服药物溶液,微球中的药物通过载体的控制释放,血药浓度峰值有很大的降低,多次给药时载药微球的药物浓度波动也有大幅度的减小;适当的溶解速率可减小药物浓度波动,同时也满足治疗所要求的浓度值.     

聚乳酸载萘普生微球形貌控制

用静电喷雾技术制备了聚乳酸/萘普生(PLA/NPX)复合微球,用扫描电子显微镜(SEM)观察微观形貌,研究了NPX添加量、溶剂种类、电压和针头内径对微球形貌影响。结果表明,当NPX添加量小于20%、电压为18 kV、针头直径为0.6 mm、接收距离为15 cm、溶剂为二氯甲烷时,微球的分散较为均匀,随着NPX含量的增加,导致颗粒粘附、团聚;二氯甲烷中添加乙醇导致微球表面凹陷,微球平均粒径由5.18μm降低至2.41μm;增加电压使得复合微球平均粒径减小,且电压过大增加微球形貌不规则程度;针头内径降低至0.25 mm,复合微球平均粒径由5.18μm降低至3.8μm,平均粒径显著降低。     

Understanding self-accelerated water diffusion within poly-lactic acid via molecular dynamics simulation

Poly-lactic acid(PLA) is widely used as a controlled drug release material and the diffusion property of water within the polymer matrix is closely related to the drug release profile. This paper studies the water diffusion in PLA by molecular dynamic simulations. Free volume analysis indicates that water molecules are expected to fill in the free volumes of the polymer matrix forming water clusters at low water content. Along with the increase of the water concentration, the polymer starts to swell and the density of the system starts to drop.Due to the high mobility of water within water cluster, the calculated diffusion coefficient dramatically increases along with the incensement of water content. Thus, we conclude that the diffusion of water is a self-accelerate process, with higher mobility of water in the case where more water exists.     

Effect of solvent quality on Poiseuille flow of polymer solutions in microchannels: A dissipative particle dynamics study

The Poiseuille flows of polymer solutions for varying quality solvents in microchannels have been simulated using dissipative particle dynamics. In particular, the velocity distributions and the polymer migration across the channel have been investigated for good, athermal, and poor solvents. The velocity profiles for all three kinds of solvent deviate from the parabolic profile, and the velocity profile of the athermal solvent falls in between the good solvent and the poor solvent. For the athermal solvent, a migration away from the wall due to the hydrodynamic interactions between the chains and the wall is observed, and a migration away from the channel center due to the different chain Brownian diffusivities is also observed. For the good solvent, because of the more stretched polymer chains, the migration away from the wall is stronger than that for the athermal solvent. However, the migration away from the channel center is not observed for good solvents. For the poor solvent, the hydrodynamic interaction within the chains is screened, and the polymer chains migrate toward the wall and appear to be absorbed by the wall. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47345.     

重质油稳定性的耗散粒子动力学模拟

重质油的稳定性关乎其开采、储运及加工过程安全。准确的重质油稳定性判定方法对重质油生产及加工过程具有重要指导意义,然而重质油稳定性的经验判定法存在一定的局限性。从理论层面建立重质油稳定性的判定方法将提高重质油稳定性的预测准确度,本文基于耗散粒子动力学方法（DPD）模拟了不同重质油体系分子的微观聚集态。模拟结果表明,重质油体系的沥青质聚集率与胶体不稳定指数（C.I.I.）及稳定性判定图的判定结果吻合,验证了模拟体系的准确性。在此基础上,基于DPD模拟结果对C.I.I.及稳定性判定图的局限性进行了讨论,提出了改进的稳定性判定图用于重油稳定的快速判定。提出的重质油稳定性判定方法有望用于实际工业过程。     

重质油稳定性的耗散粒子动力学模拟

重质油的稳定性关乎其开采、储运及加工过程安全。准确的重质油稳定性判定方法对重质油生产及加工过程具有重要指导意义,然而重质油稳定性的经验判定法存在一定的局限性。从理论层面建立重质油稳定性的判定方法将提高重质油稳定性的预测准确度,本文基于耗散粒子动力学方法（DPD）模拟了不同重质油体系分子的微观聚集态。模拟结果表明,重质油体系的沥青质聚集率与胶体不稳定指数（C.I.I.）及稳定性判定图的判定结果吻合,验证了模拟体系的准确性。在此基础上,基于DPD模拟结果对C.I.I.及稳定性判定图的局限性进行了讨论,提出了改进的稳定性判定图用于重油稳定的快速判定。提出的重质油稳定性判定方法有望用于实际工业过程。     

Effect of molecular architecture on the morphology diversity of the multicompartment micelles: A dissipative particle dynamics simulation study

Dissipative particle dynamics simulation is performed to study the sensitive influence of the molecular architecture and/or segment sequence on the morphology diversity of the multicompartment micelles. The multicompartment micelle morphologies formed by ABC triblock copolymers with various molecular architectures, such as the linear, the pentalinear, the cyclic, the star-like, the tetra-arm, and the π-shape are investigated, and different morphologies of the multicompartment micelles, for example, worm-like, “hamburger”, sheet-like with pores, “sweet potato” with alternating layers, sheet-like with cylinder-inclusion, and three-dimensional network are observed in this work. The density profiles and the radial distribution functions are calculated to characterize the structures of the multicompartment micelles. The preparation of complex multicompartment micelles can be fulfilled by simply changing the segment sequence and molecular architecture such as adding new bonds and grafting points.     

Dissipative particle dynamics studies on the interface of incompatible A/B homopolymer blends in the presence of nanorods

Dissipative particle dynamics (DPD) simulations are used to investigate the effect of nanorods on the interface of immiscible A/B homopolymer blends. The nanorods are constructed by a string of beads connected through the spring forces, and then their rigidity is achieved depending on the angle forces. For the low volume fraction and/or aspect ratio, nanorods lead to broaden the interfacial width, D and decrease the interfacial tension, γ_S with the increase of the volume fraction. There is also a pronounced linear relationship. For the high volume fraction and/or aspect ratio, the variation of D and γ_S is found to depend on Onsager’s dimensionless parameter ψν, where ψ and ν are the volume fraction and aspect ratio of nanorods in the systems, respectively. Two scaling D ∼ (ψν)³ and γ_S ∼ (ψν)² are constructed. These results indicate that nanorods can indeed be used as a compatibilizing agent of immiscible blends as mentioned in reference [J. Chem. Phys. 2008, 128, 054901] and improve the interfacial characteristics, only when the parameters (ψν) in the correct range are chosen.     

PAMAM树状大分子负载和释放阿霉素的耗散粒子动力学模拟

采用耗散粒子动力学模拟方法研究了药物输送载体聚酰胺-胺（PAMAM）树状大分子对抗癌药物阿霉素（DOX）的负载和释放行为。构建了PAMAM树状大分子的粗粒化模型,该模型能准确地重现树状大分子的构象性质。考察了PAMAM树状大分子代数（G）对DOX负载以及pH环境对DOX释放的影响。模拟结果表明,PAMAM树状大分子主要通过疏水作用将DOX包封于内部空腔,G6和G7 PAMAM树状大分子的负载能力较强,因为其孔隙率较高,内部有更多的疏水空腔。在低pH环境下,PAMAM树状大分子结构发生变化,DOX分子能快速地从其中释放,主要原因是PAMAM的伯胺、叔胺和DOX伯胺发生质子化,质子化基团间的静电排斥作用使得PAMAM树状大分子发生溶胀,导致其内部空腔暴露,促进了DOX的释放。本工作可以为基于树状大分子的药物输送体系的设计和优化提供参考。     

Multicompartment micelles formed from star-dendritic triblock copolymers in selective solvents: A dissipative particle dynamics study

Dissipative particle dynamics method was used to study the multicompartment micelles formed from star-dendritic triblock copolymers in selective solvents, in which particular attention was paid to the effects of dendritic structure. The simulations show that the dendritic structure not only influences the morphology and the formation process of multicompartment micelles formed, but also the response of the micelle structure to solvent quality. The information obtained is useful for the future design of multicompartment micelles for practical applications, especially in the field of drug delivery.     

Mechanism analysis of poly(lactic acid) particles formation by mesoscale simulation

In this work, the mechanism analysis of Poly(DL ‐lactic acid) (PLA) particles formation is investigated by dissipative particle dynamics (DPD) simulations. The polymer PLA is usually as a carrier at the drug deliver system (DDS), first, the mechanism analysis of PLA particles formation was preceded on the basis of the blank PLA particles. At the same time, the formation of PLA particles for drug delivery systems has been investigated. The results of DPD simulations indicate that the formation of PLA particles with drug or not, consists of three steps: (1) aggregation‐individual PLA chains got aggregated with each other in solution; (2) formation and disruption of PLA particles; (3) solidification of PLA particles. At the same time, the effects of PLA, drug content on the aggregation morphology are investigated, which indicates the PLA particles with drug or not aggregated and formed is spherical particles, drug molecules are amorphously and homogeneously distributed inside the PLA matrix, the size of PLA particles increases with increasing the initial PLA content and drug content in the solution. The content of DMF is gotten when PLA chains and drug molecules begin to aggregate and form the particles. These could be used to guide the experimental preparation of PLA blank particles and DDS with desired properties. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

SBA-15介观相形成过程的耗散粒子动力学模拟

采用耗散粒子动力学方法（dissipative particle dynamics,DPD）,以介孔分子筛SBA-15的合成原料P123/TEOS/H₂O为研究体系,模拟了P123/TEOS超分子自组装行为,及剪切力作用下介孔分子筛SBA-15六角介观相的形成过程。结果表明：在水溶液中,P123与TEOS两相能够发生协同作用自组装形成超分子聚集体（胶束）,该胶束由疏水的PPO球核、亲水的PEO球壳以及聚集包裹在P123外部的TEOS组成;引入稳恒剪切力后,P123/TEOS超分子聚集体则会逐渐转变成规整的六角结构,并最终形成SBA-15六角介观相,这与实际材料的TEM电镜图片相吻合。可以说,DPD模拟方法是一个研究有序介孔分子筛SBA-15形成机理的有效手段,可为实验合成提供介观层面上的重要信息。此外,还拓展了DPD模拟在超分子自组装介观尺度研究方面的新应用。