蛋白质药物靶向传输的多糖载体的化学修饰

介绍了传统药物传输系统的缺陷和药物控制传输系统的特点,文中表明,控制的药物传输可以使药物通过多聚糖载体可传输到靶向位置,从而起到控制治疗的作用.多聚糖如海藻酸盐、胶质、右旋糖苷、凝胶已在制药应用中用于或正试验用于药物的靶向传输.它们稳定、无毒且可在小肠中被酶降解,利用具有特定化学和物理性质的多糖载体的微胶囊可实现蛋白质药物的靶向传输.通过几丁聚糖的化学修饰改变其性能的研究已有较多报道,包括作者提出的一种新的修饰方法.     

新型聚合物聚乙二醇-胆酸(PEG-CA)自组装为胶束负载药物的研究

设计并合成了一种具有特定结构的新型聚合物:聚乙二醇-胆酸(PEG-CA),并分别采用核磁共振、红外光谱等表征手段确定聚合物的结构,然后通过Zeta-Plus电位粒径仪测得其自组装后胶束的粒径大小及分布。最后测定了聚乙二醇-胆酸(PEG-CA)胶束负载阿霉素(DOX)的载药量。实验结果表明聚合物聚乙二醇-胆酸(PEG-CA)具有作为纳米药物载体的药物输送的潜在应用。     

血管内皮生长因子受体靶向的紫杉醇胶束的制备及其缓释效果

利用PLGA-PEG嵌段聚合物的两亲性质制备了3种不同PEG分子量的内部包载药物的血管内皮生长因子受体靶向胶束APRPG-PEG-M。通过对制剂粒径分布、zeta电位、包封率及载药量等方面的考察,确定处方和制备工艺,并考察其制剂学性质。制备的靶向胶束呈球形或类球形,粒径109.7~119.9nm、包封率89.2%~91.5%,在体外释药试验中48h累积释放量为47.8%~60.0%,表现出明显的缓释效果。制备的紫杉醇靶向胶束在体外对药物释放具有良好的缓释效果。     

羟基喜树碱半乳糖化十六酰壳聚糖胶束的制备及表征

制备羟基喜树碱半乳糖化十六酰壳聚糖胶束(HCPT-GHCM),并考察其包封情况.方法:以半乳糖化十六酰壳聚糖(GHC)为载体材料,采用乳化溶剂挥发法制备羟基喜树碱聚合物胶束,应用正交试验考察药物/载体比例、油/水相体积比、超声时间对载药聚合物胶束包封率的影响并进行优化.结果:超声时间对胶束的包封率影响最大,其次依次为药物/载体比例和油/水相体积比.最佳条件为:药物/载体比例0.2:1,油/水相体积比1:7,超声时间40min.制备的载药胶束拉径为250nm～300nm,zeta电位约为10mV,包封率为75.96%.结论:所制备的HCPT-GHCM包封率较高,粒径分布均匀,对羟基喜树碱有增溶效果.     

主-被动靶向细胞内还原引发释放的聚合物纳米胶束抗癌药物

先用开环聚合(ROP)合成大分子的RAFT试剂(PCL-SS-DMP),然后采用可逆加成-断裂链转移(RAFT)法,合成了亲水性的N-(2-羟丙基)甲基丙烯酰胺(HPMA)和主动靶向配体叶酸单体丙烯酰胺-叶酸(AA-FA),制备了具有主动靶向还原敏感性的两亲性嵌段共聚物(PCL-SS-b-PHPMA-b-PFA),用核磁共振(1 HNMR)对其结构进行表征.此共聚物在水溶液中可自组装形成聚合物胶束,由透射电子显微镜(TEM)和动态光散射(DLS)表征可知胶束为尺寸约100nm的球形颗粒,用DLS观察到胶束粒径在10mmol二硫苏糖醇作用下随时间的增加而逐渐增大.以抗癌药物阿霉素(DOX)为模型药物,研究载药胶束在模拟人体环境中的控释行为.用四氮唑盐还原法(MTT)研究不同浓度的聚合物胶束对人宫颈癌HeLa细胞的细胞毒性,并评价载药胶束在细胞中的抗癌效果.结果表明,PCL-SS-b-PHPMA-b-PFA可作为包载DOX的一种新型纳米材料,载药胶束的体外释放呈明显的还原依赖性,且具有较好的体外抗肿瘤活性,有望成为理想的抗肿瘤药物载体.     

半乳糖化棕榈酰壳聚糖的制备

目的：制备新型的壳聚糖衍生物——半乳糖化棕榈酰壳聚糖。方法：以壳聚糖为原料,甲磺酸条件下与棕榈酰氯反应得两亲性棕榈酰壳聚糖,然后通过与活化乳糖酸反应制备半乳糖化棕榈酰壳聚糖,并应用FT-IR、H1-NMR对其结构进行表征,通过芘荧光探针法测定其临界胶束浓度。结果：半乳糖化棕榈酰壳聚糖的FT-IR及H1-NMR图谱均出现了棕榈酰基的特征峰,且棕榈酰基的取代度为1.8,其临界胶束浓度为8.96μg/mL。结论：制备了新型的半乳糖化棕榈酰壳聚糖,其具有较好的溶解性能和较低的临界胶束浓度,有望作为难溶性药物的主动靶向纳米聚合物胶束载体。     

纳米技术在药物传递方面的应用

纳米技术在生物医药方面发挥了越来越重要的作用。在药物传递方面,纳米粒子作为药物载体,可使其具有靶向性,并可控制其缓释能力、通透性及作用时间。本文对纳米粒子作为药物载体的研究进展及其应用,包括脂质体、聚合物、磁性纳米粒子、纳米金和纳米乳剂等进行了综述。     

多药传递系统在药物联合治疗中的应用

介绍聚合物/药物配合体多药物传递系统、脂质体多药物传递系统、聚合物微胶束多药物传递系统等几类典型的多药物传递系统(multi-drug delivery system,MDDS).综述上述多药物传递系统在疾病的多药联合治疗及联合诊断、成像、治疗等领域的研究进展.以期为MDDS的设计及临床药物更有效的治疗提供参考,具有重要开发应用价值.     

基于普朗尼克F127构筑纳米胶束的制备研究

聚合物胶束是一种新型的给药系统,其疏水核适用于装载各种难溶性药物,作为疏水药物的载体可以增加疏水药物的水溶性和稳定性.采用直接溶解法将阿霉素(DOX)—脱氧胆酸钠(NaDC)复合物的混悬液作为药物加入到一定浓度的普朗尼克F127胶束分散体中,磁力搅拌5h后用0.45 μm的乙酸纤维素过滤器过滤,将滤液倒入10 mL容量...     

天然药物靶向给药系统的研究进展

脂质体、微球、乳剂等新型药物载体在天然药物靶向给药系统研究中已广泛应用。靶向给药系统的研究已取得了很大的进展,但是在生产和临床上应用还存在不少问题,应遵循传统中药理论,结合现代技术进行研究。通过查阅了近年来国内外天然药物靶向给药系统的研究进展的相关资料,并对其进行分析和整理。     

Preparation and Characterization of Polymeric Micelles from Poly（D, L-lactide） and Methoxypolyethylene Glycol Block Copolymers as Potential Drug Carriers

Amphiphilic diblock copolymers composed of methoxy polyethylene glycol (MePEG) and poly(D,L- lactide) (PDLLA) were prepared for the preparation of polymeric micelles. The use of MePEG-PDLLA as drug carriers has been reported in the open literature, but there are only few data on the application of a se- ries of MePEG-PDLLA copolymers with different lengths in the medical field. The shape of the polymeric mi- celles is also important in drug delivery. Studies on in vitro drug release profiles require a good sink condi- tion. The critical micelle concentration of a series of MePEG-PDLLA has a significant role in drug release. To estimate their feasibility as a drug carrier, polymeric micelles made of MePEG-PDLLA block copolymer were prepared by the oil in water (O/W) emulsion method. From dynamic light scattering (DLS) measurements, the size of the micelle formed was less than 200 nm. The critical micelle concentration of polymeric micelles with various compositions was determined using pyrene as a fluorescence probe. The critical micelle con- centration decreased with increasing number of hydrophobic segments. MePEG-PDLLA micelles have a considerably low critical micelle concentration (0.4-0.5 μg/mL), which is apparently an advantage in utilizing these micelles as drug carriers. The morphology of the polymeric micelles was observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The micelles were found to be nearly spherical. The yield of the polymeric micelles obtained from the O/W method is as high as 85%.     

Synthesis and evaluation of methionine and folate co-decorated chitosan self-assembly polymeric micelles as a potential hydrophobic drug-delivery system

In this study, an amphiphilic copolymer folate-succinyl-methionine-chitosan-octyl (FSMCO) was successfully synthesized step by step for self-assembling polymeric micelles. The copolymers formed micelle-like nanoparticles by their amphiphilic characteristics and structures were examined by UV-Vis absorption and Fourier transform spectroscopy. The sizes of blank and ICG derivativeloaded micelles measured by dynamic light scattering were about 170 and 140 nm, respectively, which were spherical in shape with an average zeta potential of 10 mV. Further studies on the stability showed that the micellar solutions maintain their sizes at room temperature for 1 month without distinct aggregation or dissociation. ICG derivative was much better photostable after being entrapped by the new carrier. The prepared FSMCO micelles displayed a good drug loading content (11.7%), entrapment efficiency (66.5%) and sustained release rate for the model drug fluorescein. The copolymers demonstrated weeny cytotoxicity toward Bel-7402, L02 and A549 cells when incubated for 2 d. Ligands modified micelles endowed preferable cell targeting capability and beautiful cell inhibition of HCPT-FSMCO on Bel-7402 tumor cells. This kind of polymeric micelles may be a promising nanovehicle in delivering near-infrared dyes for tumors imaging and chemotherapeutic drugs for cancer therapeutics.     

高分子药物研究进展

综述了高分子药物的研究进展，将高分子药物分为具有药理活性的高分子聚合物、高分子络合物药物、高分子微胶囊药物以及高分子载体药物4大类，并对其在药学上的应用进行了阐述．     

羧甲基壳聚糖纳米胶束的制备与光响应性研究

智能响应性聚合物胶束作为药物控释传递系统的载体引起广泛关注,其中光刺激因为可控性高、清洁高效等优点被广泛研究.该文以丁二酸酐为连接臂将1-芘甲醇(PyM)接枝到羧甲基壳聚糖(CMCS)的氨基上制得两亲性大分子(PMS-g-CMCS),然后在水溶液中自组装成光响应纳米胶束.采用动态光散射(DLS)和透射电镜(TEM)表征胶束的大小和形态,并研究光刺激前后胶束的大小变化;通过核磁和荧光研究胶束的光响应机制.结果表明该胶束为类球形核-壳结构,粒径约200 nm,且具有较好储存稳定性;在紫外(UV)光照下,能发生结构改变,其光响应机制可归因于连接PyM的酯键断裂.胶束显示出可用作疏水性药物或农药光控释放载体的潜力.     

Self-assembly and drug delivery behaviors of a novel thermo-sensitive block glycopolymer

A novel thermo-sensitive block glycopolymer based on peracetylated maltoheptaose (AcMH) and poly(2-ethyl-2-oxazoline) (PEtOz) was synthesized for the first time and characterized by hydrogen nuclear magnetic resonance (¹H NMR) spectroscopy and gel permeation chromatograph (GPC) analyses. To obtain such a block polymer, the dihydroxyl poly(2-ethyl-2-oxazoline) homopolymer (OH-PEtOz-OH) was first synthesized by cationic ring-opening polymerization of 2-ethyl-2-oxazoline (EtOz), and then coupled with the peracetylated maltoheptaose having a free hydroxyl group at the reducing end (AcMH-OH) prepared from β-cyclodextrin. It was found that the obtained block polymer could self-assemble into nanosize spherical micelles with a distinct core-shell structure in aqueous solution triggered by its amphiphilic character without any organic solvent. The model drug indomethacin (IND) was efficiently loaded into the resultant polymeric micelles, which was confirmed by ¹H NMR spectra, transmission electron microscope (TEM) and dynamic light scattering (DLS) techniques. The release behavior of IND loaded micelles was well in response to the environmental temperature change. It is suggested that the resulting micelles might be a potential targeted carrier for drug delivery.     

p-Hydroxybenzoic acid (p-HA) modified polymeric micelles for brain-targeted docetaxel delivery

Chemotherapies for brain diseases have been hampered due to the inability of transport of drug across the blood-brain barrier (BBB). In order to overcome the barrier, p-hydroxybenzoic acid (p-HA), a small molecule of benzamide analogue, was used as a ligand for brain-targeted drug delivery. The p-HA was conjugated to PEG-DSPE to form p-HA-PEG-DSPE. Docetaxel-loaded polymeric micelles were prepared by a thin-film hydration method using methoxy-poly(ethylene glycol)-distearoylphosphatidyl- ethanolamine (mPEG 2000 -DSPE) as a carrier and the p-HA-PEG-DSPE as a brain targeted material. The prepared micelles showed spherical with a mean diameter of (18±3) nm. Encapsulation efficiency and drug loading were (83.49±1.3)%, (7.7±1.2)% for un- modified micelles and (80.65±1.6)%, (7.47±1.8)% for p-HA-modified micelles, respectively. In vitro cellular uptake experiments showed that the p-HA-modified micelles increased BCECs cellular uptake by 1.2 times compared to the unmodified micelles. Ex vivo near-infrared fluorescence imaging showed that brain uptake of the p-HA-modified micelles was 1.3-1.8 times higher than that of the unmodified micelles. In vitro cytotoxicity assay against glioblastoma cell U87 MG showed that inhibition rate of the p-HA-modified micelles increased by 1.2 times compared to that of the unmodified micelles and 1.7 times compared to that of DTX. Survival time of nude mice bearing intracranial glioblastoma showed that the lifetime of saline group, Taxotere group, mPEG-DSPE/DTX micelles group and p-HA-PEG-DSPE/DTX micelles group was 22, 27, 32 and 45.8 d, representively, which indicated that anti-glioblastoma activity of DTX could be significantly enhanced by the p-HA-modified polymeric micelles. These results demonstrated that the p-HA-modified micelles could be a promising brain-targeted drug delivery system for hydrophobic drugs against glioblastoma.     

表面活性剂在微胶囊表面吸附的动力学模拟

采用耗散粒子动力学(Dissipative Particle Dynamics,DPD)方法,模拟了表面活性剂在接枝型两亲性共聚物形成的微胶囊表面的吸附情况。对亲水性聚合物的接枝密度和长度对表面活性剂吸附的影响进行了研究。结果表明,接枝亲水性聚合物能有效的阻止表面活性剂在微胶囊表面的吸附,当接枝长度不变时,接枝密度在2~5根枝时既能有效的阻止表面活性剂的吸附,又能保持微胶囊的形状,此时,亲水部分与憎水部分的体积比在0.1667~0.4167之间;当接枝密度固定时,接枝长度大于4个珠子时就能有效的阻止表面活性剂的吸附。     

多糖类微凝胶的制备及其在缓控释给药系统中的应用

文章综述了淀粉、纤维素及右旋糖苷等3类多糖类微凝胶的制备方法及其在缓控释给药系统中的应用研究进展.多糖类微凝胶的制备方法主要有:物理法、化学共沉淀法、反相微乳液法、微乳-溶剂挥发法及全水相法等,其中不使用有害溶剂的全水相法最具发展潜力.多糖类微凝胶在药物缓控释、降低药物毒害性、提高药物的生物利用度等方面均显示出优势,已成功应用于胰岛素、布洛芬等多种药物的包载与缓控释.     

雷帕霉素缓释胶束的制备及其释放行为

以生物可降解的树状高分子材料作为药物载体,采用透析的方法制备了雷帕霉素缓释胶束。通过扫描电镜、动态光散射仪及紫外分光光度计对载药胶束的形貌、粒径及体外释放行为进行了表征及研究。结果表明:载药胶束为中空结构的囊泡,载药后粒径明显增大,载药量和包封率分别提高到40%和91%,体外释放结果显示其缓释作用明显,Gompertz一级函数模型较为真实地反应其释放行为。