聚酯型高分子纳米载药系统研究进展

目的介绍PCL、PLGA、PLA等聚酯型高分子纳米载药系统的研究进展。方法查阅相关文献,总结归纳纳米粒的制备、性能特点、在药物输送系统DDS中的应用等。结果聚酯型高分子纳米载药系统制备简单,有靶向、缓释特征,在DDS中应用较广。结论聚酯型高分子纳米载药系统可作为有前途的新型给药系统。     

聚酯型高分子纳米载药系统研究进展

目的介绍PCL、PLGA、PLA等聚酯型高分子纳米载药系统的研究进展。方法查阅相关文献,总结归纳纳米粒的制备、性能特点、在药物输送系统DDS中的应用等。结果聚酯型高分子纳米载药系统制备简单,有靶向、缓释特征,在DDS中应用较广。结论聚酯型高分子纳米载药系统可作为有前途的新型给药系统。     

还原响应型透明质酸/聚己内酯纳米粒子的制备及其体外抗肺癌效应研究

目的： 构建一种具有良好生物安全性、肿瘤主动靶向性及能实现药物快速释放的药物纳米载体。方法： 通过点击化学反应制备由二硫键连接的两亲性透明质酸/聚己内酯接枝聚合物;采用动态光散射、透射电镜对聚合物的自组装行为进行研究;通过体外药物释放实验探究药物载体还原响应控制释放特性;通过流式细胞术、激光共聚焦显微镜等技术对A549细胞内吞噬载药纳米粒子的机制进行研究;结果： 所制备的含二硫键的接枝聚合物可自组装形成粒径大约为75 nm的球形纳米粒子;该纳米粒子在质量浓度为200 μg·mL^-1时仍具有较好的生物安全性;当纳米粒子包载阿霉素后其粒径增大至128 nm,且药物在还原性条件下可实现快速释放;载药后的纳米粒子经透明质酸/CD44受体间的相互作用快速进入肿瘤细胞内,并能显著抑制肿瘤细胞生长。结论： 本研究合成的含二硫键的透明质酸/聚己内酯接枝聚合物具有良好生物相容性、肿瘤靶向性及药物控制释放特性,作为抗肿瘤药物载体具有一定优势。     

星形聚合物胶束作为药物载体的研究进展

星形聚合物胶束是一类新型纳米药物载体,它具有独特的分枝结构,所形成的单分子胶束具有理想的粒径和稳定性,可使难溶性药物有效增溶,降低药物毒性,延长体循环时间,提高生物利用度和安全性。星形聚合物胶束作为药物载体具有良好的缓释效果,通过在聚合物表面接枝功能基团可产生靶向释放效果,聚酯结构的星形聚合物还具有良好的降解性能,不在体内蓄积产生毒副作用。本文对星形聚合物的合成及其胶束作为药物载体的理化性质、载药优势、制备方法等的研究进展进行综述。     

PLGA纳米粒抗肿瘤药物载体的研究进展

目的：阐述近年来PLGA 纳米粒作为抗肿瘤药物载体的研究进展。方法归纳国内外最新的文献报道,对PLGA纳米粒作为抗肿瘤药物载体在主动与被动靶向方面的应用研究进展进行综述。结果由于纳米材料可以增强抗肿瘤药物的靶向作用,而PLGA是经FDA认证的具有生物降解性及生物相容性的功能高分子有机聚合物,已经被广泛地应用于抗肿瘤药物的载体研究。结论 PLGA纳米粒作为抗肿瘤药物载体具有广阔的应用前景。     

影响聚酯微球中药物释放的因素

聚酯材料因其原料易得、容易加工、生物相容性好、具有可生物降解性等优点,已经成为当今药物载体材料中的一大研究热点。现综合国内外的有关报道对可生物降解聚酯材料作为药物载体制备微球制剂的研究进展进行了综述。针对目前限制聚酯材料微球制剂临床应用存在的问题,从聚合物、药物、制备工艺、附加剂、辐射灭菌5个方面对影响聚乳酸(PLA)和聚乳酸乙醇酸共聚物(PLGA)缓释微球中药物释放的因素进行了重点介绍,为研究聚酯微球中药物的释放提供思路。     

鱼藤酮纳米凝胶的制备与表征

目的以三嵌段聚酯聚乙二醇共聚物 （PLGA PEG PLGA）为材料制备鱼藤酮纳米凝胶。方法采用薄膜分散 水化法制备鱼藤酮纳米凝胶,并分别对其粒径分布、药物分散状态和药物释放特性等理化特性进行研究。结果鱼藤酮纳米凝胶平均粒径为120 nm,多分散系数0.190,药物主要以非晶型均匀分散在纳米凝胶中;纳米凝胶具有良好的缓释效果,10 d释放＜40%,药物的释放与释放介质和纳米凝胶中的药物含量密切相关。结论该方法成功制备了难溶性药物鱼藤酮的纳米凝胶制剂,能够显著改善其水溶性和药物释放特性。     

多功能纳米载体

目前所用药物纳米载体（如脂质体，胶束，纳米乳，聚合物纳米粒）有很多有益特性，如血液循环时间延长，使药物在痛灶聚集；靶向作用；增强细胞内渗透作用；体内载体造影；生理环境敏感的药物释放。但多功能纳米载体仍很少，如长循环免疫脂质体。多功能药物纳米载体可显著增强许多治疗和诊断试剂的效果。本文论述了多功能纳米载体的当前状况和发展方向，主要关注结合长循环性、靶向性、胞内渗透性和造影能力的多功能纳米载体。     

聚合物纳米粒子作为药物载体的研究与应用

目的:介绍聚合物纳米粒子作为药物载体的研究与应用现状。方法:参阅国内外文献,进行分析、归纳和总结。结果:聚合物纳米粒子可作为疏水药物、靶向药物和生物大分子药物的载体制备聚合物纳米粒的材料与方法具有多样性。结论:可生物降解的聚合物纳米粒载药系统具有可控释、靶向、保护生物大分子药物的活性等优势,是一个很有发展潜力的药物传递系统。     

紫杉烷衍生物/PEG-PLA胶束的制备及理化性质研究

目的采用两亲性聚合物材料聚乙二醇-聚乳酸(PEG-PLA)为载体,紫杉烷衍生物TM-2作为模型药物,制备出高载药量的胶束制剂。方法采用凝胶渗透色谱法、差示扫描量热法、核磁、红外等方法对聚合物材料性质进行表征,芘荧光探针法测定材料的临界胶束浓度,通过薄膜水化法制备聚合物胶束,并对胶束溶液进行冻干,考察胶束的粒径、电位、载药量、体外释放等理化性质。结果胶束粒径约为20 nm,载药量在10%左右,冻干后体外释放可在72 h内释放80%以上。结论以无定型形式存在的TM-2通过薄膜水化法与聚合物自组装增加其在水中的溶解度,体外释放起始可能是因附在粒子表面或近表面的药物快速释放,随后通过载体孔道扩散而缓慢释放。     

PLGA微球的修饰及其应用

微球作为新型的药物载体系统已广泛用于临床研究,高分子化合物材料聚乳酸-羟基乙酸(pdy lactic-co-glycolic acid,PLGA)因其良好的生物相容性和生物可降解性备受关注。近年来,PLGA微球的研究一直是热门,针对其释放缺陷出现了很多复合修饰方法,主要包括环糊精、壳聚糖、聚乳酸、明胶、泊洛沙姆、聚乙烯亚胺等高分子材料的联用、针对末端基团进行化学修饰以及制备成核壳型微球,在保证包封率的情况下大大降低突释,改善药物释放曲线,从而在药物传递、基因治疗、影像诊断、组织工程等领域得到了广泛的应用。     

Modeling of drug release from biodegradable polymer blends

Numerous mathematical models that predict drug release from degradable systems have been reported. Most of these models cater only to single step, diffusion-controlled release while a few attempt to describe bi-phasic release. All these models, however, are only applicable to drug release from single (unblended) degradable polymer systems.In this paper, we propose and test novel models for drug (notably paclitaxel) release from films made of neat poly (ε-caprolactone) PCL, neat poly (dl-lactide-co-glycolide) PLGA and their blends. The model developed for neat PCL consists of two terms: initial burst and diffusional release. On the other hand, a more complex model proposed for tri-phasic release from neat PLGA consists of burst release, degradative (relaxation-induced) drug dissolution release and diffusional release.Finally, this very first model to predict release from blend of PLGA and PCL was developed based on a heuristic approach. Drug distribution between PCL-rich and PLGA-rich phases is dictated by partition coefficient, and the overall fraction of drug release is a summation of drug released from the two phases. The proposed models exhibited good prediction of the experimental data.     

Formulation, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 and PLGA 85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12-15 micron and 12-22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

Formulation,Characterization, and Evaluation of Ketorolac Tromethamine-Loaded Biodegradable Microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 andPLGA85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12–15 micron and 12–22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with pluronic P105/poly(caprolactone) copolymers

A novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic/poly(caprolactone) (P105/ PCL50) has been developed with the purpose of improving in vitro release and in vivo circulating time of PTX in comparison to the current Taxol injection. This study was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of the PTX-loaded, biodegradable, polymeric, P105/PCL50 micelle system. The drug-loaded micelles were prepared by dialysis using the hydrophobic drug, PTX, and the nonionic surfactant Pluronic P105 modified with a low molecular weight PCL. The results of dynamic light scattering (DLS) experiment indicated that the PTX-loaded micelles had a mean size of approximately 150 nm with narrow size distribution (polydispersity index < 0.3). The in vitro release study showed that the release of PTX from the micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic assessment in rats, in which t1/2 beta and AUC of the PTX micelle formulation were 4.0 and 2.2-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTX micelle formulation not only decreased drug uptake by the liver, but also prolonged drug retention in the blood, and increased the distribution of drug in kidney, spleen, ovaries and uterus. These results suggested that the P105/ PCL50 polymeric micelles may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for i.v. administration of PTX.     

Comparative study of some biodegradable polymers on the entrapment efficiency and release behavior of etoposide from microspheres

Etoposide-loaded biodegradable microspheres of poly lactic-co-glycolide (PLGA) 50:50, PLGA 75:25, and polycaprolactone (PCL) were prepared by simple o/w emulsification solvent evaparation method and characterized by size analysis and microscopy. The influence of drug to polymer ratio on the entrapment of etoposide was studied. Of all the three types of microspheres, polycaprolactone microspheres (PCL MS) showed the highest entrapment efficiency (94.64%), followed by PLGA 75:25 microspheres (PLGA 75:25 MS) (88.64%) and PLGA 50:50 microspheres (PLGA 50:50 MS) (79.19%). The drug to polymer ratio of 1:20 gave the highest entrapment efficiency for all the three types of microspheres. The in vitro release of etoposide from the three microsphere formulations were studied in phosphate buffer pH 7.4 (pH 7.4 PB) containing 0.1% Tween 80. The microspheres showed an initial burst release, which was highest from the PLGA 50:50 MS and least from the PCL MS. PCL MS microspheres showed the lower and slow drug release than the remaining formulations. The release of etoposide from all the three microsphere formulations followed Higuchi's diffusion pattern. The microspheres in the dissolution medium for 28 days appeared irregular in shape and slightly fragmented.     

Paclitaxel-loaded polyester nanoparticles prepared by spray-drying technology: in vitro bioactivity evaluation

Paclitaxel (PTX), an antimicrotubular agent used in the treatment of ovarian and breast cancer, was encapsulated in nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL) polymers using the spray-drying technique. Morphology, size distribution, drug encapsulation efficiency, thermal degradation and drug release were characterized. MCF7 cells were employed to evaluate the efficacy of the systems on cell cycle and cytotoxicity. The particle size was in the range 0.8–1?µm. The incorporation efficiency of PTX was more than 80% in all NPs obtained. In vitro drug release took place during 35 days, and drug release rates were in the order PCL?>?PLGA 50:50?>?PLGA 75:25. Unloaded NPs showed to be cytocompatible at MCF7 cells. PTX-loaded NPs demonstrated the release of the drug block cells in the G2/M phase. All PTX-loaded formulations showed their efficacy in killing MCF7 cells, mainly PTX-loaded PLGA 50:50 and PLGA 75:25 that cause a decrease in cell viability lower than 20%.     

Paclitaxel-loaded polyester nanoparticles prepared by spray-drying technology: in vitro bioactivity evaluation

Paclitaxel (PTX), an antimicrotubular agent used in the treatment of ovarian and breast cancer, was encapsulated in nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL) polymers using the spray-drying technique. Morphology, size distribution, drug encapsulation efficiency, thermal degradation and drug release were characterized. MCF7 cells were employed to evaluate the efficacy of the systems on cell cycle and cytotoxicity. The particle size was in the range 0.8-1?μm. The incorporation efficiency of PTX was more than 80% in all NPs obtained. In?vitro drug release took place during 35 days, and drug release rates were in the order PCL?>?PLGA 50:50?>?PLGA 75:25. Unloaded NPs showed to be cytocompatible at MCF7 cells. PTX-loaded NPs demonstrated the release of the drug block cells in the G2/M phase. All PTX-loaded formulations showed their efficacy in killing MCF7 cells, mainly PTX-loaded PLGA 50:50 and PLGA 75:25 that cause a decrease in cell viability lower than 20%.     

PCL/PEG core/sheath fibers with controlled drug release rate fabricated on the basis of a novel combined technique

A novel core/sheath fiber preparation method, which included the processes of blend electrospinning to produce the core fiber and UV-induced graft polymerization to fabricate the outer polymeric shell, was presented to provide designated fibers with different shell thicknesses. A hydrophilic drug, salicylic acid (SA), was loaded in the representative poly(?-caprolactone) (PCL)/polyethylene glycol (PEG) core/sheath fibers, performed according to this combined technique. FTIR analysis indicated that the existence of hydrogen bonds between SA and the PCL matrix improved drug compatibility. Field emission scanning electron microscopy (FESEM) images indicated that the morphology and the diameter distribution of fibers changed significantly after the graft polymerization procedure. All the core/sheath fibers became more flexible and thicker compared with the core fiber. The water contact angle (WCA) test also noted the differences of these two fibers: PCL/PEG core/sheath fibers with cross-linked PEG surface exhibited more hydrophilic property. Moreover, in vitro SA release tests were conducted to explore the relationship between the PEG shell thickness and the drug release rate. A typical biphasic release mechanism was observed for the PCL/PEG core/sheath fibers, and their sustained release rates were controlled by the PEG shell thickness in a linear correlation.     

New approach to treating spinal cord injury using PEG-TAT-modified,cyclosporine-A-loaded PLGA/polymeric liposomes

Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT)-modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co-glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI. The PLGA/CsA NPs were successfully constructed. In vitro drug release studies have demonstrated that the sustained release of CsA from PLGA/CsA NPs occurs over ～25?h. The in vivo study presented here showed that injured animals that received PLGA/CsA NPs through the tail vein, exhibited a significant up-regulation of growth-associated protein-43 (GAP-43) expression and an increased number of GAP-43-stained neurons compared with animals that received CsA or the vehicle alone. The improvement in neurological function was also evaluated by the Basso–Beattie–Bresnahan (BBB) open-field test. Moreover, fluorescein isothiocyanate (FITC)-attached PLGA/CsA NPs were successfully aggregated in the intact spinal cord 4?h after injection. Our data suggest that PLGA/CsA NPs have the potential for use as a new treatment method for SCI.