聚乙二醇修饰的共聚物纳米粒研究进展

可生物降解的聚合物纳米粒作为药物输送载体有很多优势，如可控释，靶向等。但是，由于聚合物纳米粒经静脉经给药后，数秒或数分钟内会被皮网状系统清除而无法普遍应用，为了克服这一缺点，越来越多的研究者引入亲水性组分聚乙二醇（PEG）对聚合物进行修饰，以避免其被内皮肉状系统摄取。聚乙二醇的引入不仅会影响聚合物纳米粒的生物降解行为，而且会影响药物的释放，体内分布等行为，本文综述了聚乙二醇修饰的共聚物纳米粒的制备，稳定性，载体，体外释药，体内分布，毒性等方面的研究进展，并对其前景进行预测。     

聚乳酸/聚乙二醇琥珀酸酯-姜黄素纳米粒的制备及体外评价*

背景：聚乳酸及其共聚物是一类具有良好生物相容性的可降解高分子材料,已被广泛用于可生物降解型药物缓释或靶向给药系统中。 目的：探索载药纳米粒制备条件对包封率和载药量的影响,确定最佳制备工艺条件。 方法：以维生素E1000聚乙二醇琥珀酸酯(TPGS)为乳化剂、姜黄素为模型药物、聚乳酸为载体材料,采用O/W型乳化-溶剂挥发法制备聚乳酸-姜黄素纳米粒,以包封率和载药量为主要指标,单因素实验探索影响两指标的主要因素,再正交试验设计优化制备工艺。 结果与结论：通过正交试验设计制备聚乳酸-姜黄素纳米粒的最佳工艺为：水油相比10∶1,聚合物浓度15 g/L,药物浓度3 g/L,乳化剂TPGS浓度0.03%。以此工艺制备的载药纳米粒外形圆整光滑,粒度分布较为均匀,平均粒径为167.5 nm,包封率为89.52%,载药量为13.72%,纳米粒前期突释不明显具有良好的缓释作用。该工艺稳定、简单可行,优化制备工艺得到的聚乳酸-姜黄素纳米粒粒径适中、包封率和载药量较高。     

药物缓释体抗胶质瘤的效用分析

目的:对药物缓释系统抗胶质瘤中载体材料的类型、材料生物学特点及其应用进行了归纳总结。方法:作者应用计算机检索PubMed(http://www.ncbi.nlm.nih.gov/PubMed)及CNKI数据库(www.cnki.net/index.htm),在标题和摘要中以"聚乳酸,载体,间质内化疗"或"Polylacticacid,vector,interstitialchemotherapy"为检索词进行检索。选择文章与药物缓释体,聚乳酸,载体及其应用效果相关,同一领域文献则选择近期发表或发表在权威杂志文章。共纳入13篇文献。结果:作为药物缓释体的载体应具备良好的生物相容性、高分子聚合物和降解产物均无毒,适当的物理机械性能及可成型性,具有可以调节的降解速度。目前间质内化疗治疗胶质瘤复发,即缓释控释给药系统,不需频繁给药,能在较长时间内维持体内有效的药物浓度,从而可以显著提高药效和降低毒副作用。与静脉化疗药物治疗相比,毒副作用少且疗效好。结论:选择具有良好生物学特性的可降解高分子为载体的化疗缓释体,进行间质内化疗较静脉化疗有明显优势,极具开发潜能。     

体外研究聚合物P(DLLA-co-TMC)的降解性能与释药行为

目的 研究P(DLLA-co-TMC)聚合物的体外降解性能与释药行为,且探讨该聚合物作为长效避孕释放载体的可行性.方法 以PBS溶液为溶媒研究P(DLLA-co-TMC)的降解性能;以P(DLLA-co-TMC)聚合物为载体制备含孕二烯酮的载药片,并通过蒸馏水浸泡载药片研究载药体系的体外释药行为.结果 P(DLLA-co-TMC)聚合物前期降解较慢,第30天和第90天失重率分别为10.0%和12.3%,后期降解速率较快,第120天的失重率为59.3%;P(DLLA-co-TMC)的载药片前期释药速率较大,出现"暴释现象",后期释药速率减缓并逐渐趋于平稳,第100天时累计释放率为5.64%.结论 P(DLLA-co-TMC)聚合物降解性能良好、释药效果明显,有望通过体内研究使含孕二烯酮的P(DLLA-co-TMC)聚合物载药系统应用于长效埋植避孕.     

可降解载药原位水凝胶在眼后段药物缓释的有限元分析

目的 探究在水凝胶的降解行为下药物在眼后段的扩散过程,为评估局部药物浓度和优化可降解水凝胶的眼内释药性能提供研究基础。方法 通过有限元分析法建立可降解载药原位水凝胶在眼后段的药物传递模型。模型考虑水凝胶的降解作用、眼内压和视网膜色素上皮细胞主动吸收引起的对流作用,以及眼内吸收清除作用对药物扩散的影响,探究药物在眼后段中的浓度变化情况。结果 释药过程中,眼内药物主要向后部扩散,载药水凝胶的释药速度明显慢于溶液药物。结论 可降解水凝胶通过防止药物中心移动和限制凝胶内部药物扩散的方式延长药物在眼后段的停留时间,合理调整原位水凝胶注射位置和降解性能参数能有效提高其治疗效果。     

具有S—型降解共聚(L—丙交酯/甘油酯)的药物释放系统的体内特性

为了对药物释放系统的研究,作者曾通过羟基酸和丙交酯在无催化剂的作用下直接缩聚合成系列生物可降解聚酯,平均分子量小于10000的低分子聚合物,处理易变形,载体与药物易混合,聚合物降解易控制。目前作者研究发现L-丙交酯与甘油酯高分子共聚物可作为一种可降解性材料,平均分子量为16900～41300。通过具有催化剂存在的开环聚合作用而制备,表明体内降解产生明显的S-型降解模型,而具有高分子量的生物可降解S-型聚合     

药物控释用海藻酸钠、壳聚糖、明胶的研究进展

由于许多药物如肽或蛋白质药物,物理化学性质不稳定,在胃肠道中极易降解.因此,在口服释药设计中,pH敏感水凝胶如海藻酸钠、壳聚糖和明胶作为药物控制释放载体日益引起人们的关注.将针对三种天然高分子材料的来源、结构、性能及共混改性展开讨论.     

药物从多孔骨架聚合物系统中恒速释放的机理

以组分的连续性方程为基础 ,建立了药物从多孔骨架聚合物系统中释放的数学模型。在模型中引入相对渗透速度来刻画药物释放过程中不同机理的影响。对药物从多孔骨架聚合物系统中non -Fickian扩散现象进行了研究 ,特别对药物溶出机制控制的恒速释药现象进行了解释。     

体外研究聚合物P（DLLA—co—TMC）的降解性能与释药行为

目的 研究P（DLLA—CO-TMC）聚合物的体外降解性能与释药行为,且探讨该聚合物作为长效避孕释放载体的可行性。方法以PBS溶液为溶媒研究P（DLLA-CO-TMC）的降解性能;以P（DLLA—CO—TMC）聚合物为载体制备含孕二烯酮的载药片,并通过蒸馏水浸泡载药片研究载药体系的体外释药行为。结果P（DLLA-CO-TMc）聚合物前期降解较慢,第30天和第90天失重率分别为10．0％和12．3％,后期降解速率较快,第120天的失重率为59．3％;P（DLLA-CO-TMC）的载药片前期释药速率较大,出现“暴释现象”,后期释药速率减缓并逐渐趋于平稳,第100天时累计释放率为5．64％。结论P（DLLA-co-TMC）聚合物降解性能良好、释药效果明显,有望通过体内研究使含孕二烯酮的P（DLLA—CO—TMC）聚合物载药系统应用于长效埋植避孕。     

超声可控释药体系研究进展

超声可控释药体系是一种新兴的靶向给药及基因转运方法。以超声敏感材料作为药物或基因转送的载体,当超声辐照于靶组织或靶器官时, 靶体内载体可定向释放出包裹或附着的基因或药物, 实现对负载药物的定时定量定点释放和提高药物输送效率或基因转染率的目的。文中对超声可控释药体系的作用机制、超声敏感载体材料及生物医学应用等方面进行综述,最后对该领域目前存在的问题和今后的发展方向提出了一些看法。     

生物可降解载药纤维的成形特性的研究

为了开发一种用于治疗肿瘤的局部定位缓释给药系统，本研究在室温条件制备了生物可降解的聚乳酸（PLLA）纤维，并且详细研究了制备过程中的处方工艺条件（聚合物分子量、聚合物浓度、注射速度、出口口径以及固化液的种类）对聚乳酸纤维的成形特性（纤维直径、纤维的表面与内部结构以及纤维的结晶度）的影响。此外，还在聚乳酸纤维上上载了一种脂溶性模型药物（尼莫地平），并对载药纤维的体外释放性质进行了研究。结果表明，这类载药纤维可以成为一种有开发前景的局部定位给药缓释系统。     

膜缓控释给药系统促进损伤组织的修复

背景：目前研究多注重缓控释给药膜的缓控释效果及其生物相容性,也有开展缓控释给药膜参与损伤组织修复的机制研究,其中干细胞是损伤组织修复的关键因素,但干细胞与缓控释给药膜之间的联系尚未得到足够关注。 目的：分析膜缓控释给药系统在组织损伤修复中的研究现状与进展。 方法：以“缓释系统,膜,药物载体,组织损伤修复,干细胞归巢;sustained-release system,membrane,drug delivery,injuries and repairs of tissue,stem cell homing”为关键词,采用计算机检索Pubmed数据库、中国知网、Elsevier数据库1992年1月至2012年12月有关膜缓控释给药系统临床应用及实验研究的文章。 结果与结论：在膜缓控释给药系统中高分子材料几乎成了药物和生长因子在传递、渗透过程中不可分割的组成部分。虽然药物缓释系统的发展与制膜技术都在不断的更新,但距离完全达到理想的应用标准还有一定的差距,如不具备主动吸引干细胞定向迁移与分布的生物学功能。近年来膜缓控释给药系统出现新的发展方向,即不仅能起到诱导干细胞定向分化的作用,也能诱导干细胞向损伤部位定向分布,从而促进损伤组织再生修复。     

口服缓释、控释制剂的常用技术及临床应用

背景：新型缓释、控释制剂加速药物制剂的研究速度,使得药物剂型及制剂质量不断提高。 目的：分析了目前临床上常用的口服缓释、控释制剂的常用技术及临床应用情况。 方法：以“缓释,控释,生物制药,药物载体,高分子材料”或“delayed release,drug delivery carrier,polymer material;controlled release”为检索词,应用计算机检索CNKI和PubMed数据库中2000-02/2011-04关于口服缓释、控释药物的相关文章。选入文章内容与高分子药用材料及缓释、控释药物制剂技术及和临床应用有关,排除重复研究。 结果与结论：理想的剂型是指药物对靶部位选择性高,且能推迟必要的药效时间,迅速而完全地排泄,尽量不对其他脏器与组织产生不良反应。在缓释制剂的设计中,需要充分考虑药物的水溶性、油水分配系数、化学稳定性以及蛋白结合率等理化性质和生物学性质对缓释制剂释药行为的控制;生理因素对缓释制剂的设计,如给药部位、胃肠蠕动、首过效应、血流供应、患者疾病状态、药物作用的靶器官等也需考虑。     

胰岛素缓释载体材料应用研究与问题

BACKGROUND: Sustained-release carriers of insulin shaped as microspheres made of different biomaterials have become an issue of concern. OBJECTIVE: To summarize the carrier materials and methods to prepare sustained-release microspheres of insulin. METHODS: Wanfang and PubMed databases were retrieved by computer for articles related to sustained-release carriers of insulin published from 1997 to 2015. The search terms were “insulin, controlled-release carrier, biomaterials” in Chinese and English, respectively. RESULTS AND CONCLUSION: Natural biodegradable polymer materials are preferred to prepare sustained-release microspheres of insulin, including gelatin, alginate, chitosan and its derivatives. These natural materials have good biocompatibility, degradability, film-forming and microsphere-forming abilities. Synthetic biodegradable polymer materials as carrier materials can promote drug stability and effective utilization, and realize targeted drug delivery. According to different physicochemical properties of materials, sustained-release carriers of insulin that meet different requirements can be prepared using emulsion-chemical crosslinking, spray drying and solvent evaporation methods. This review provides new insight into the development of stable drug carriers.     

Brain biocompatibility of a biodegradable, controlled-release polymer in rats

We report the biocompatibility in the rat brain of a controlled-release, biodegradable polymer, the polyanhydride poly-[bis(p-carboxyphenoxy)propane-sebacic acid] copolymer (PCPP-SA) in a 20:80 formulation. The biodegradable polyanhydride can be used for drug delivery directly into the brain, circumventing the difficulties posed by the blood-brain barrier and avoiding the consequences of having to administer toxic doses systematically to reach therapeutic doses in the central nervous system. The tissue reaction in the presence of PCPP-SA was compared to that seen with other standard neurosurgical implants. Fifty-six adult Sprague-Dawley rats were assigned to one of seven groups and underwent bilateral frontal lobe implantation of PCPP-SA (42 hemispheres), Surgicel (oxidized regenerated cellulose) (35 hemispheres), or Gelfoam (absorbable gelatin sponge) (35 hemispheres). None of the animals showed any behavioral changes or neurological deficits suggestive of either systemic or localized toxicity from the biodegradable polyanhydride, all surviving to the scheduled data of sacrifice. PCPP-SA evoked a well localized inflammatory reaction, comparable to that of Surgicel, which resolved as the PCPP-SA polymer degraded over five weeks. The biodegradable polyanhydride has been shown in this study to be nontoxic and biocompatible in the rat brain, when compared to standard neurosurgical implants.     

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system’s chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and ¹H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.     

A microfabrication method of a biodegradable polymer chip for a controlled release system

A simple microfabrication method for a controlled-release drug-delivery system has been designed using biodegradable polymeric microchips. Microholes were made in a poly(L-lactic acid) plate and dyes were cast in each well. After drying, the wells were sealed with polymers having different biodegradation rates using a mold that had hollows corresponding to the wells. The polymers were prepared by mixing polylactides with the co-polymers. The sealing was confirmed by ultrasonication. The plate was incubated in phosphate-buffered saline and the dye released from the plate as the degradation proceeded was detected spectrophotometrically. The higher the degradation rate of the polymer sealing, the faster the sealed dye was released. This biodegradable biochip is useful for the design of controlled-release drug-delivery systems.     

A microfabrication method of a biodegradable polymer chip for a controlled release system

A simple microfabrication method for a controlled-release drug-delivery system has been designed using biodegradable polymeric microchips. Microholes were made in a poly(L-lactic acid) plate and dyes were cast in each well. After drying, the wells were sealed with polymers having different biodegradation rates using a mold that had hollows corresponding to the wells. The polymers were prepared by mixing polylactides with the co-polymers. The sealing was confirmed by ultrasonication. The plate was incubated in phosphate-buffered saline and the dye released from the plate as the degradation proceeded was detected spectrophotometrically. The higher the degradation rate of the polymer sealing, the faster the sealed dye was released. This biodegradable biochip is useful for the design of controlled-release drug-delivery systems.     

Size and temperature effects on poly(lactic-co-glycolic acid) degradation and microreservoir device performance

The component materials of controlled-release drug delivery systems are often selected based on their degradation rates. The release time of a drug from a system will strongly depend on the degradation rates of the component polymers. We have observed that some poly(lactic-co-glycolic acid) polymers (PLGA) exhibit degradation rates that depend on the size of the polymer object and the temperature of the surrounding environment. In vitro degradation studies of four different PLGA polymers showed that 150 microm thick membranes degraded more rapidly than 50 microm thick membranes, as characterized by gel permeation chromatography and mass loss measurements. Faster degradation was observed at 37 degrees C than 25 degrees C, and when the saline media was not refreshed. A biodegradable polymeric microreservoir device that we have developed relies on the degradation of polymeric membranes to deliver pulses of molecules from reservoirs on the device. Earlier molecular release was seen from devices having thicker PLGA membranes. Comparison of an in vitro release study from these devices with the degradation study suggests that reservoir membranes rupture and drug release occurs when a membrane threshold molecular weight of 5000-15000 is reached.     

Implantable microencapsulated dopamine (DA): a new approach for slow-release DA delivery into brain tissue

Biodegradable controlled-release systems constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional and histochemical observations, indicating that implantation of DA microcapsules into striatal tissue assures a prolonged release of the transmitter in situ. This technology has considerable potential for basic and possibly also clinical research.