纳米粒作为抗肿瘤药物载体的研究进展

近年来纳米粒作为抗肿瘤药物载体的制备、作用机制及其体内外药效学评价等方面取得较大的进展.纳米粒作为抗肿瘤药物的载体具有许多优点,并可通过多种方式提高所携药物的药效学特征,显示纳米粒在肿瘤治疗领域具有广泛的应用前景.     

嵌段共聚物胶束作为抗肿瘤药物载体的研究进展

嵌段共聚物胶束作为抗肿瘤药的载体，可降低网状内皮系统对抗肿瘤药物的识别和摄取、减少药物的肾排泄及其在正常组织的积蓄；增加了药物在血中的稳定性和在肿瘤组织的积蓄量，是一种长效、高效、安全的抗肿瘤药物载体。嵌段共聚物胶束在肿瘤治疗中的应用具有广阔的发展前景，为肿瘤治疗带来了新的曙光。     

纳米立方液晶系统作为抗肿瘤药物载体的研究进展

摘 要对近年来纳米立方液晶系统作为药物载体在抗肿瘤方面的研究进展进行综述。介绍纳米液晶的结构、特点、制备方法和常用材料,及其在肿瘤方面的应用。纳米立方晶具有提高药物溶解度和稳定性的优势,并具有良好的生物相容性,作为新型纳米药物载体广泛受到人们关注。     

脂质体作为抗肿瘤药物载体的应用研究

目前，应用脂质体作为抗肿瘤药物载体已成为趋势。脂质体可明显提高抗肿瘤药物的靶向性，延长药物的作用时间，降低药物毒性。作者对国内外普通脂质体和修饰脂质体（包括长循环脂质体、免疫脂质体、温度敏感脂质体和pH敏感脂质体）的相关文献进行了综述。结果表明，脂质体是抗肿瘤药物的理想载体，在肿瘤治疗中有着广阔的应用前景。     

纳米胶束作为药物载体的研究进展

药剂学中以表面活性剂或高分子载体材料形成的胶束为载体制成的药物胶柬制剂正受到越来越多的关注,而粒径为纳米尺寸的纳米胶束作为药物的载体具有许多独特的优势,如缓控释及靶向特性、与细胞和组织的生物相容性等优点,在新型载药系统领域显示了良好的应用前景。本文简要综述了纳米胶束的性质、形成机理、载体材料、制备方法、体内外释药特性及在药物载体方面的应用研究。     

抗肿瘤药物靶向载体系统的研究与开发

综述肿瘤靶向给药的基础和抗肿瘤药物靶向载体系统的发展。分类介绍普通被动靶向载药系统（如微乳、传统脂质体、聚合物纳米粒、固体脂质纳米粒、纳米脂质载体、药-脂结合物纳米粒等）、表面修饰的被动靶向载药系统及主动靶向载药系统（如免疫脂质体、免疫聚合物纳米粒及受体-配体介导靶向纳米载体）的研究与开发。在传统药物制剂的基础上，发展抗肿瘤药物的新型靶向载体系统，改善药物在体内的代谢动力学特性，增加药物定向富集到肿瘤部位甚至肿瘤细胞内，提高疗效，降低毒副作用，是近年来备受关注的课题。     

蒽环类抗肿瘤药物不良反应发生机制及其新型药物载体系统的研究进展

蒽环类抗肿瘤药物抗肿瘤谱广、作用强大,对治疗白血病、乳腺癌、淋巴瘤等多种恶性实体瘤及血液系统恶性肿瘤时有着很好的疗效,但其临床使用中出现了很多不良反应。综述蒽环类抗肿瘤药物不良反应的临床表现和发生机制,以及其新型药物载体系统的应用文献,并对其研究进展做了分析。     

靶向抗肿瘤药物的研究进展

随着非细胞毒性靶向抗肿瘤药物的应用,肿瘤患者生存质量显著提高,甚至长期带瘤生存也成为可能.随着肿瘤发生机制的逐步揭示,细胞、分子靶向治疗在肿瘤治疗中的作用也越来越受到重视,这为肿瘤治疗开辟了一片新的前景.     

脂质体作为药物载体研究进展

脂质体是由磷脂分散在水中形成的具有双分子层的直径仅有几十纳米至数微米的超微球状粒子.1965年Bangham等[1]发现脂质体,20世纪70年代Gregoriadis等[2]首先将脂质体作为药物载体应用.由于脂质体具有独特的作用特点,而受到越来越多的关注.靶向性是脂质体作为药物载体的主要目标之一,脂质体是治疗肝寄生虫病、利什曼病等网状内皮系统疾病理想的药物载体,在肿瘤治疗方面,利用脂质体的靶向作用,将脂质体作为抗肿瘤药物的有效载体而得到广泛应用.另外,药物被包埋在脂质体中缓慢释放,在血循环中脂质体药物要比游离药物有更长的滞留时间,因而延长了药物的作用时间,起到长效作用[3].药物由于有脂质体包封将提高被包封药物的稳定性,还能保护定向至某些需治疗的靶器官或组织中释放,使这些靶器官或组织药物浓度提高,提高了药物的疗效,以此同时,另外一些器官或组织药物浓度分布很少,避免药物对这些器官或组织的影响,从而降低了药物的毒性[4].近年来脂质体用作基因转移的有效载体[5,6],较病毒类载体有更大的优势,受到广泛的关注.     

聚酰胺-胺树状大分子作为药物载体的体外增溶、缓释试验

目的:考察以聚酰胺-胺树状大分子(PAMAM)作为喹诺酮类药物载体在增溶、缓释方面的作用。方法:根据文献合成PAMAM,并作结构分析;以巴洛沙星为模型药物,检测不同代数不同浓度的PAMAM对巴洛沙星的增溶作用;同时用不同代数的PAMAM与巴洛沙星复合,检测PAMAM对巴洛沙星体外释放的影响,以及在水及模拟肠液中的释放情况。结果:巴洛沙星在水中溶解度约为1.5g·L-1,完全释药时间约为4h。随着PAMAM代数和浓度的增加巴洛沙星溶解度增加(2～5.25g·L-1),PAMAM与巴洛沙星复合物在水中24h释放80%,在模拟肠液中72h释放73%。结论:PAMAM对巴洛沙星具有增溶、缓释作用,有可能促进其制成具有缓释作用的溶液剂或注射剂。     

铂类抗癌药物奥沙利铂原料药的稳定性研究

目的考察铂类抗癌药物奥沙利铂原料药的稳定性。方法分别在强光(4 500 lx±500 lx)照射10 d、高温(60℃)存放10 d、高湿(25℃,相对湿度90%±5%)存放10 d、加速试验(40℃±2℃,相对湿度75%±5%)6个月、长期试验(25℃±2℃,相对湿度60%±10%)12个月后,考察奥沙利铂原料药的性状、鉴别以及溶液的外观、pH、比旋度、有关物质、杂质D、干燥失重和含量变化。结果经光照试验、高湿试验、高温试验、加速试验和长期试验后,奥沙利铂原料药的各项指标均符合质量标准要求。结论奥沙利铂原料药稳定性较好。     

PEG化聚酰胺-胺树状大分子的合成及其作为喜树碱药物载体的研究

目的 合成聚乙二醇(PEG)化3.0代聚酰胺-胺(PAMAM)树状大分子,并研究PEG-3.0PAMAM作为喜树碱载体的传递系统对喜树碱的溶解、释放性能和光敏性等方面的影响.方法 合成PEG350-3.0PAMAM树状大分子并确证结构;用HPLC检测3.0代PAMAM及PEG350-3.0PAMAM对喜树碱溶解性能的影响;分别将3.0代PAMAM和PEG350-3.0PAMAM与喜树碱复合,检测二者对喜树碱体外释放的影响;通过光照实验考查PEG350-3.0PAMAM对喜树碱的光敏作用.结果 PEG350-3.0PAMAM较之同代PAMAM对喜树碱具有更强的增溶作用和更快的释药速度,同时可改善喜树碱的光敏性,增加其稳定性.结论 PEG350-3.0PAMAM作为喜树碱载体是一种很有潜力的新型药物传递系统.     

Long-Circulating PEGylated Polycyanoacrylate Nanoparticles as New Drug Carrier for Brain Delivery

Purpose. The aim of this study was to evaluate the ability of long-circulating PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue. Methods. Biodistribution profiles and brain concentrations of [¹⁴C]-radiolabeled PEG-PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticles, and uncoated PHDCA nanoparticles were determined by radioactivity counting after intravenous administration in mice and rats. In addition, the integrity of the blood-brain barrier (BBB) after nanoparticles administration was evaluated by in vivo quantification of the diffusion of [¹⁴C]-sucrose into the brain. The location of fluorescent nanoparticles in the brain was also investigated by epi-fluorescent microscopy. Results. Based on their long-circulating characteristics, PEGylated PHDCA nanoparticles penetrated into the brain to a larger extent than all the other tested formulations. Particles were localized in the ependymal cells of the choroid plexuses, in the epithelial cells of pia mater and ventricles, and to a lower extent in the capillary endothelial cells of BBB. These phenomena occurred without any modification of BBB permeability whereas polysorbate 80-coated nanoparticles owed, in part, their efficacy to BBB permeabilization induced by the surfactant. Poloxamine 908-coated nanoparticles failed to increase brain concentration probably because of their inability to interact with cells. Conclusions. This study proposes PEGylated poly (cyanoacrylate) nanoparticles as a new brain delivery system and highlights two requirements to design adequate delivery systems for such a purpose: a) long-circulating properties of the carrier, and b) appropriate surface characteristics to allow interactions with BBB endothelial cells.     

Development and Pharmacokinetics of Galactosylated Poly-L-Glutamic Acid as a Biodegradable Carrier for Liver-Specific Drug Delivery

Purpose. A biodegradable carrier for the liver-specific delivery of drugs was developed using poly-L-glutamic acid (PLGA) modified with galactose (galactosylated PLGA or Gal-PLGA), and its feasibility was investigated in mice. Methods. ¹¹¹In-PLGA and ¹¹¹In-Gal-PLGAs were injected in mice and their distribution and biodegradation properties were studied. Results. After intravenous injection, ¹¹¹In-PLGA was rapidly eliminated from the plasma and recovered mainly in the kidneys and urine. Approximately 15% of the dose was recovered in the liver, predominantly in the nonparenchymal cells. ¹¹¹In-Gal-PLGAs were taken up by the liver parenchymal cells. Derivatives having 16 or more galactose residues were taken up by the liver to a higher extent (>60% of the dose). The hepatic clearance of ¹¹¹n-Gal-PLGAs correlated with their number of galactose residues. ¹¹¹In-Gal₁₈-PLGA was degraded into low-molecular weight products in the liver. Conclusions. The advantageous in vivo properties of Gal-PLGA as a liver-specific biodegradable carrier of drugs were demonstrated in mice.     

磁靶向给药系统的研究进展

磁靶向给药系统有利于提高药物疗效,降低毒副作用,为癌症化疗开辟了新的途径,可望在不久的将来。广泛用于临床。介绍和评价了磁靶向给药系统的制备、性质和药效等,并综述该系统的研究进展。     

Macromolecular Carrier Systems for Targeted Drug Delivery: Pharmacokinetic Considerations on Biodistribution

This review article describes the current status and future perspectives of site-specific drug delivery by means of macromolecular carrier systems. Basic aspects and recent advances of targeted delivery of 1) conventional drugs, 2) protein drugs, and 3) gene medicines including antisense oligonucleotides and plasmid DNA, are reviewed from a pharmacokintic perspective. Successful in vivo application of macromolecular carrier systems requires pharmacokinetic considerations at whole body, organ, cellular and subcellular levels. The integration of simultaneous research progress in the multidisciplinary fields such as biochemistry, cell and molecular biology, pharmacology, and pharmacokinetics will accelerate the emergence of marketed drugs with macromolecular carrier systems.     

Proliferation Indices as Molecular Pharmacodynamic Endpoints in Evaluation of Anticancer Drug Effect in Human Solid Tumors

Purpose. The present study compared proliferative indices, i.e. incorporation of DNA precursor (i.e. thymidine or TdR, and bromodeoxyuridine or BrdU) and expression of proliferating cell nuclear antigen (PCNA), as molecular pharmacodynamic endpoints in evaluation of anticancer drug effect in human solid tumors. Methods. Tumor specimens obtained from patients were grown as histocultures. After treatment with doxorubicin, mitomycin C, and/or paclitaxel, cells labeled by [³H]TdR were identified using autoradiography, and cells labeled by BrdU and PCNA were identified using immunohistochemical techniques. Drug effect was measured as reduction of DNA precursor-labeled cells or PCNA-expressing cells. Results. The results indicate that (a) the two DNA precursors, TdR and BrdU, labeled the same cells and resulted in identical pharmacodynamics, (b) the pharmacodynamics established using inhibition of DNA precursor incorporation were qualitatively and quantitatively different from the pharmacodynamics established using inhibition of PCNA expression, (c) the inhibition of PCNA expression was erratic in some tumors, and (d) the differences in pharmacodynamics established using the two end points are drug-specific, with greater differences for paclitaxel than for mitomycin C. Conclusions. The erratic results measured by the PCNA labeling method suggest that this method may be less reliable than the conventional DNA precursor labeling method. The finding of identical pharmacodynamics of doxorubicin and paclitaxel established using BrdU and [³H]TdR indicates that the two precursors are interchangeable. Because the methodology for detecting BrdU incorporation requires less time and does not require the use of radioactivity, we conclude that inhibition of BrdU incorporation represents a useful endpoint for evaluating the antiproliferative activity of anticancer drugs in human solid tumors.     

474例抗肿瘤药品不良反应/事件报告分析

目的对淮安市抗肿瘤药品不良反应事件发生情况及特点进行分析,为临床合理用药提供参考。方法采用回顾性分类统计,对淮安市2004年1月至2012年12月共474例的抗肿瘤药品不良反应/事件病例报告进行综合分析。结果抗肿瘤药品不良反应涉及中老年患者最多;顺铂、紫杉醇、奥沙利铂所致药品不良反应居前3位;静脉用药不良反应发生率最高;抗肿瘤药品不良反应累及的系统-器官以血液系统损害最常见。结论临床上应加强对抗肿瘤药品不良反应的预防和监测。