聚合物胶束作为肿瘤靶向给药载体的研究

聚合物胶束是近年来出现的一种新型胶态药物载体,具有很多优良的性能,如体内外稳定性高、良好的生物相容性、难溶性药物的增溶作用等.它可以作为靶向肿瘤的给药载体,通过多种机制,如环境响应的聚合物胶束、特异性配基耦合的聚合物胶束、免疫聚合物胶束、通透性增强与滞留(EPR)效应、肿瘤的血管系统等途径来实现药物靶向给药.现主要讨论肿瘤给药的靶向策略和聚合物胶束作为靶向肿瘤给药载体的研究进展.     

聚合物胶束在肿瘤靶向给药系统中的研究进展

摘 要 聚合物胶束作为一种有效的药物运送载体已经受到广泛关注,其在肿瘤治疗方面具有高效,长效和高载药量等优势。本文综述了聚合物胶束的类型,制备材料,载药方法,主要讨论了肿瘤靶向载药系统中的靶向策略和应用实例。     

载药聚合物胶束的制备和肿瘤靶向性研究进展

聚合物胶束具有增溶难溶性药物、选择性靶向、P-gp抑制以及改变药物摄取途径等特点,作为药物传递系统具有广泛的应用前景。本文着重综述载药聚合物胶束的制备方法与肿瘤靶向策略的研究现状及进展。     

聚合物胶束用于口服给药的研究进展

聚合物胶束是由两亲性聚合物自发形成的热力学稳定体系,它对难溶性药物具有良好的增溶效果。许多具有良好活性的药物由于溶解性差,其口服给药受到限制。将聚合物胶束作为口服给药的载体可以显著改善药物的溶解性,增加透过生物膜的药量,进而提高药效。此外,聚合物组成和性质具有多样性,利用聚合物的这一特性可以制备出对pH值、温度敏感或者具有黏膜黏附性的胶束。在提高药物溶解度的同时,通过改变药物在胃肠道中的释放过程,进一步提高其生物利用度。本文主要介绍聚合物胶束在口服给药方面的研究进展,分析并总结其作为口服给药载体应用的特点和前景。     

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。     

聚合物胶束在肿瘤治疗中的研究进展

聚合物胶束在肿瘤治疗方面具有高效、长效及高载药量等优势.本文简单比较了聚合物胶束与其它纳米级药物载体(如高分子直接键合药物、树枝状聚合物、脂质体)在临床应用上的优缺点.综述了聚合物胶束在肿瘤主动靶向性、环境刺激响应释药及医学成像等方面的研究进展.     

多功能聚合物胶束的最新研究进展

由两亲性聚合物形成的胶束是一种很有发展前景的纳米级药物载体。聚合物胶束作为药物载体具有许多优势,如载药能力强、粒径小、体内循环时间长、具有主动和被动靶向性等特点。聚合物胶束的最新研究主要集中在使其功能更加完善方面,即多功能聚合物胶束的研究。现按照多功能聚合物胶束到达目标部位后发挥效用的方式对其进行分类,并对其最新研究进展和应用进行综述。     

天然高分子聚合物胶束的研究进展

聚合物胶束作为药物载体,具有稳定性好,增加难溶性药物溶解度,使药物靶向肿瘤部位并缓慢释放,降低不良反应,提高药物生物利用度等优点,是一种优良的载药系统。天然高分子材料由于来源丰富,生物相容性好,降解产物对人体无毒而备受重视。通过查阅文献,笔者综述了天然高分子材料聚合物胶束的研究进展。     

聚合物胶束在经皮给药系统中的应用

摘 要 目的：综述聚合物胶束作为药物载体在经皮传递系统中的应用进展。方法: 根据国内外发表的最新文献,对聚合物胶束的制备方法、促进皮肤渗透的机制、释药过程及其在经皮给药系统中的应用进行分析与讨论。结果: 聚合物胶束具有增加难溶性药物的溶解度,促进药物的经皮吸收等作用,作为药物载体在经皮传递系统的应用越来越广泛。结论:聚合物胶束可作为药物载体被广泛用于经皮给药系统的研究中,具有较好的发展前景。     

药物纳米载体——聚合物胶束的研究进展

目的对目前聚合物胶束作为药物纳米载体的国内外研究进展进行综述。方法参考近年来国内外文献50篇,从聚合物胶束的类别和构成,药物的包载方法,药物从聚合物胶束中的释放,聚合物胶束的稳定性,聚合物胶束的表征,聚合物胶束对药物的药动学和体内分布的影响以及聚合物胶束作为药物载体的应用等几个方面系统地介绍了其研究进展。结果聚合物胶束包括自聚集胶束,单分子胶束和交联的胶束,可采用化学结合法、物理包载和聚离子复合法包载药物;药物分子在聚合物胶束中的分布以及聚合物的降解行为决定了药物的释放速度;聚合物胶束的热力学和动力学稳定性与其结构组成密切相关;载药聚合物胶束可改变药物的药动学和体内分布;目前聚合物胶束已被用于作为肿瘤药物、难溶性药物的载体,也可作为药物药物经皮传递载体和药物的缓释载体,发展前景较好,但同时也面临挑战。结论聚合物胶束作为药物的纳米载体具有广泛的应用前景。     

Synthesis and evaluation of biotin-conjugated pH-responsive polymeric micelles as drug carriers

pH-Responsive polymeric micelles have been investigated as drug carriers for chemotherapy. Ligand-mediated polymeric micelles, which can penetrate the target tumors due to their high binding affinity to a specific receptor on the surface of tumors, were developed to achieve targeted drug delivery. In this study, biotin-conjugated methoxypoly(ethylene glycol)-grafted-poly(β-amino ester) was prepared for active and pH-sensitive tumor targeting. These polymers were modified by cholesteryl chloroformate to improve the hydrophobicity of the micelle core. The structure of the biotin-conjugated polymer was confirmed by (1)H NMR spectroscopy, and the existence of biotin at the surface of the polymeric micelles was evaluated by an 4'-hydroxyazobenzene-2-carboxylic acid/avidin (HABA/avidin) binding assay at different pHs. The micelle properties were determined by dynamic light scattering and the result showed that the mean size of the polymeric micelles was approximately 20 nm. For cancer therapy, doxorubicin (DOX) was loaded into the polymeric micelles with a high loading efficiency. From the in vitro cellular uptake results, the biotin-conjugated polymeric micelles can effectively release doxorubicin at acidic tumor cells compared to the micelles without biotin. Overall, biotin-conjugated pH-responsive polymeric micelles have great potential to be used as drug carriers.     

pH响应性聚合物胶束及其在抗癌药物给药系统中的研究进展

 聚合物纳米粒作为一种有效的药物运送载体已经受到广泛的关注,具有环境响应性的聚合物胶束的制备及应用是目前引人瞩目的研究方向。最近,pH响应性聚合物胶束已被用作抗癌药物的运送载体,其显著的优势就是能够靶向给药于病灶部位,从而降低不良反应,提高抗癌药物的化疗指数。文中综述了pH值响应性的聚合物胶束的两种主要制备策略,即依赖于共聚物骨架中的“可滴定”基团;引入可被酸降解的连接臂,还介绍了pH值响应性聚合物胶束在抗癌药物给药系统中的应用。     

Enhanced tumor-targeted delivery of anticancer drugs by folic acid-conjugated pH-sensitive polymeric micelles

In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid (FA), the ligand of folate receptor (FR) over-expressed in the most cancer cells, modified pH-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin (DOX) by combination of pH-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and pH-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified pH-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and pH-triggered drug release. In conclusion, the designed FR-targeted pH-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs.     

新型多功能可生物降解PEG-PLA/PLGA/PCL聚合物纳米抗肿瘤药物载体的研究进展

PEG-PLA/PLGA/PCL聚合物药物载体因具备可生物降解性、高包封率、靶向运输、可控释放及可修饰的特性,在癌症治疗的应用中得到越来越广泛的关注。然而,PEG-PLA/PLGA/PCL聚合物材料作为抗癌药物的递送载体仍然面临诸多的挑战：1）聚合物药物载体结构的不稳定性;2）靶向运输的效果不明显;3）药物在肿瘤组织释放不完全等。因此,设计出新型的PEG-聚酯类聚合物药物载体成为研究的前沿和热点。本文综述了近年来国内外研究学者在构建多功能性的PEG-聚酯类聚合物纳米抗癌药物载体的研究成果,从提高结构稳定、增强靶向能力以及刺激响应释放三种设计理念对不同的纳米载药体系进行讨论、分析和总结。     

Amphiphilic polysaccharide-hydrophobicized graft polymeric micelles for drug delivery nanosystems

Self-assembled amphiphilic graft copolymers in aqueous solution to form polymeric micelles, have received growing scientific attention over the years. Among the polymeric micelles, hydrophobicized polysaccharides have currently become one of the hottest researches in the field of drug delivery nanosystems. It is attributable to such appealing properties as small particle size and narrow size distribution, distinctive core-shell structure, high solubilization capacity and structural stability, tumor passive localization by enhanced permeability and retention (EPR) effect, active targeting ability via tailored targeting promoiety, long-circulation property and facile preparation. The polymeric micelles self-assembled by hydrophobicized polysaccharides can be employed as targeted drug delivery nanosystem by including thermo- or pH-sensitive components or by attaching specific targeted moieties to the outer hydrophilic surface. Beside encapsulation of water-insoluble drugs, hydrophobicized polysaccharide polymeric micelles can complex with charged proteins or peptide drugs through electrostatic force or hydrogen bond, and serve as an effective non-viral vector for gene delivery. In the latter case, polymeric micelles can not only markedly protect these macromolecules from degradation by protease or ribozymes, but also increase the gene transfection efficiency. This review will highlight the state of the art self-assembled mechanism, characterization, preparation methods and surface modification of hydrophobicized polysaccharide polymeric micelles and their recent rapid applications as drug delivery nanosystems.     

Dendrimeric micelles for controlled drug release and targeted delivery

This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery.     

Advances in polymeric micelles for drug delivery and tumor targeting

A plethora of formulation techniques have been reported in the literature for targeting drugs to specific sites. Polymeric micelles (PMs) can be targeted to tumor sites by passive as well as active mechanisms. Some inherent properties of PMs, including size in the nanorange, stability in plasma, longevity in vivo, and pathological characteristics of tumor allow PMs to be targeted to the tumor site by a passive mechanism called the enhanced permeability and retention effect. PMs formed from an amphiphilic block copolymer are suitable for encapsulation of poorly water-soluble, hydrophobic anticancer drugs. Other characteristics of PMs such as separate functionality at the outer shell are useful for targeting the anticancer drug to tumor by active mechanisms. PMs can be conjugated with many ligands such as antibody fragments, epidermal growth factors, α₂-glycoprotein, transferrin, and folate to target micelles to cancer cells. Application of heat or ultrasound are the alternative methods to enhance drug accumulation in tumoral cells. Targeting using micelles can also be directed toward tumor angiogenesis, which is a potentially promising target for anticancer drugs. PMs have been used for the delivery of many anticancer agents in preclinical and clinical studies. This review summarizes recently available information regarding targeting of anticancer drugs to the tumor site using PMs.From the Clinical EditorThis review summarizes recent developments related to targeted anticancer drug delivery to tumor sites using polymeric micelles via active and passive mechanisms. Polymeric micelles can be conjugated with diverse ligands such as antibodies fragments, epidermal growth factors, α2-glycoprotein, transferrin, folate to target micelles to cancer cells.