抗癌药物多相脂质体研制及抗癌活性初步筛选

本文报道一些抗癌药物多脂质体的制备,如苦杏仁苷、氟糖啶、β—谷甾醇、顺氯氨铂(Ⅱ)等,其制务方法采用注入一超声法。对六种抗癌药物多相脂质体都进行抑癌?,其抑瘤作用显著,毒性降低,具有一定靶向性。并且药物的稳定性增加。     

紫杉醇脂质体致过敏性休克患者的用药分析

紫杉醇脂质体是用卵磷脂等将紫杉醇进行包裹,脂质体包裹的抗癌药物进入临床始于20世纪80年代末期。脂质体作为抗癌药物的载体,具有制作简单、对机体无毒,能显著降低药物毒副作用及容易实现肿瘤靶向等优点。经过脂质体包裹后的药物,其溶解性增加,避免和极大的减少了溶媒引起的变态反应。     

由空白前体脂质体制备抗癌药物脂质体

以空白前体脂质体作为药物载体,将药物溶液分散在载体中,制成药物脂质体.空白前体脂质体对5Fu等几种抗癌药物均可达到一定的包裹率,阿霉素在一定条件下可达到85%以上,并与传统薄膜法进行了比较.抑瘤活性及毒性实验结果表明:与游离药物相比,5Fu、阿霉素等药物的抑瘤活性都有不同程度的提高.急性毒性实验表明:除AraC外,几种药物的毒性均有所降低,以顺铂最明显.     

注射用奥沙利铂对比奥沙利铂脂质体Beagle犬的解剖病理学评价

目的:比较注射用奥沙利铂和奥沙利铂脂质体对Beagle犬毒性作用的解剖病理学改变,为抗癌药物脂质体制剂的临床前安全性评价提供重要的形态学参考数据。方法:Beagle犬分为阴性对照组、空载体脂质体组、注射用奥沙利铂组、奥沙利铂脂质体低、高剂量组。静脉滴注每2周给药1次,共4次,恢复期1个月。解剖动物进行组织病理学检查。结果:与脂质体、注射用奥沙利铂和奥沙利铂脂质体相关的组织病理学变化分别为多组织器官的泡沫细胞聚集;睾丸生精细胞数量减少,附睾精子减少症和胸腺、脾脏萎缩;肝脏小肉芽肿,胸腺、脾脏萎缩。结论:通过以上同一抗癌药物不同剂型对Beagle犬的解剖病理学评价比较,为抗癌药物脂质体剂型临床前安全性评价提供了重要的形态学参考数据。     

脂质体药剂及其临床应用

脂质体药剂主要作抗癌药物及抗寄生虫药的载体、控制药物释放、提高生物利用度、增强疗效、增加稳定性等。由于其与生物膜的特殊关系，对淋巴系统的定向性和与癌细胞的亲和性，故而作为重要的一类靶向载体制剂。     

铂类抗肿瘤药物的研究现状

自从顺铂作为第一代抗肿瘤药物被开发利用以来，人们一直在寻找广谱、高活性、低毒性和无交叉耐药性的铂类抗肿瘤药物，合成和筛选出各种铂络合物。分别介绍根据不同设计思路合成的四价铂络合物、具有活性配体的铂络合物、生物载体为配体的靶向铂络合物、反式铂络合物和具有立体位阻效应的铂络合物及其抗肿瘤活性，综述当前铂类抗肿瘤药物的研究现状。     

铂类抗癌药物市场分析

目的 :了解铂类抗癌药物市场的现状及发展趋势。方法 :对顺铂、卡铂等几种铂类抗癌药物的市场状况分别加以分析。结果与结论 :铂类抗癌药物市场今后将进一步扩大 ,前景看好。     

磁性药物载体在抗肿瘤方面的研究进展

通过外加磁场的引导作用,使负载抗癌药物的磁性载体靶向定位于靶区,提高靶组织的药物浓度,有效降低药物对正常组织或细胞的毒副作用及其他不良反应。磁性药物载体还具有靶向性、缓释、控释等优点,已成为了肿瘤靶向治疗常用的新型载体系统。本文综述了磁性药物载体磁性纳米颗粒、磁性脂质体、磁性微球在肿瘤治疗与诊断中的应用进展。     

顺铂的应用及铂族金属抗癌药物的研究进展

综述了顺铂和卡铂的特点及其应用情况,对近３０年来铂类抗癌药物的研究进行了介绍和评价。它们包括顺铂类药物,卡铂类药物,环己二胺药物和四价铂类药物。     

栀子提取物类脂质体在大鼠体内的分布及靶向性研究

目的:研究栀子提取物类脂质体在大鼠体内的药物分布特点及靶向性。方法:采用改良薄膜分散法制备栀子提取物类脂质体。将30只大鼠按体质量随机均分为空白组、栀子提取物(57 mg/kg)组和栀子提取物类脂质体(131 mg/kg)组,ig相应药物,空白组ig等体积蒸馏水,每天1次,连续7 d。末次给药1 h后,取大鼠心、肝、脾、肺、肾组织,采用高效液相色谱法检测其中栀子提取物有效成分栀子苷的含量,通过药物靶向指数(DTI)定量评价栀子提取物类脂质体的体内靶向性。结果:与栀子提取物组比较,栀子提取物类脂质体组大鼠心、脾、脑组织中栀子苷含量明显增加(P<0.01),DTI分别为1.718、1.972、13.071;肝、肾组织中栀子苷含量明显降低(P<0.01),DTI分别为0.431、0.467。结论:栀子提取物类脂质体改变了栀子苷在大鼠体内的组织分布,可靶向作用于脑组织,减少了肝的首关效应。     

Drug discovery research on in vivo antitumor-active azolato-bridged dinuclear Pt(II) complexes

Cis-diamminedichloridoplatinum(II) (cisplatin), which was first introduced as a clinical anticancer agent in the 1970s, is still among the most-utilized agents in current cancer chemotherapy. The discovery of cisplatin antitumor activity has catalyzed drug discovery research on antitumor platinum coordination compounds with improved efficacy. Some of new compounds show fewer side effects or expanded clinical applications. Apart from some clinical inconveniences, such as side effects, the high therapeutic efficacy of platinum-based agents implies that further modifications may lead to more effective anticancer platinum drugs which are effective against cancers that are typically resistant to chemotherapy, such as pancreatic cancer, and platinum-refractory cancer. Most of the cisplatin analogs cause cross-resistance to cisplatin, probably because of the similar biological consequences. It is suggested that platinum complexes which interact with DNA; the most probable target molecule, through a mechanism different from that of cisplatin can provide unique anticancer spectra required for next-generation anticancer drugs. Therefore, we synthesized a series of azolato-bridged dinuclear Pt(II) complexes with a general formula, [{cis-Pt(NH(3))(2)}(2)(μ-OH)(μ-azolato)](2+), which can form 1,2-intrastrand crosslinks with a minimal DNA distortion, whereas clinical platinum-based drugs provide 1,2-intrastrand crosslink with severe DNA distortion. Indeed, they exhibit much higher in vitro cytotoxicity than cisplatin, and we have recently found one of the dinuclear Pt(II) complexes exhibits markedly high in vivo antitumor efficacy against pancreatic cancer. Here, I update our drug-discovery research on the series of azolato-bridged dinuclear Pt(II) complexes that may be more effective and safer than current anticancer chemotherapeutic agents.     

铂类抗肿瘤药物的研发进展及市场情况

近年来,铂类抗肿瘤药物的临床研究进展较快,其抗肿瘤谱广,抗肿瘤活性增强,不良反应降低,已成为目前有关抗肿瘤药物研发的重要领域。新的铂类抗肿瘤药物将从那些在临床研究中显示出低毒性、抗肿瘤谱广、与现有药物无交叉耐药性的化合物中产生。本文就其作用机制、国内外上市开发现状、国内外销售情况及国内研究开发进展等进行综述。     

Liposomal delivery of camptothecins

The use of liposomal drug delivery systems to improve the therapeutic index of pharmaceutical agents is exemplified by camptothecin-based drugs. This highly active class of anticancer agents possesses a unique mechanism of action with some inherent shortcomings, which might have been solved by liposomal formulation. Recent studies have revealed the protective action, increased tumor delivery and prolonged plasma exposure of these liposomal formulated drugs. These advances in pharmaceutical development could increase the levels of activity of these agents, as well as increase their clinical utility as new emerging anticancer therapies.     

Lanthanides as anticancer agents

The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metals and metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. A lot of metal-based drugs are widely used in the treatment of cancer. The clinical success of cisplatin and other platinum complexes is limited by significant side effects acquired or intrinsic resistance. Therefore, much attention has focused on designing new coordination compounds with improved pharmacological properties and a broader range of antitumor activity. Strategies for developing new anticancer agents include the incorporation of carrier groups that can target tumor cells with high specificity. Also of interest is to develop complexes that bind to DNA in a fundamentally different manner than cisplatin, in an attempt to overcome the resistance pathways that have evolved to eliminate the drug. This review focuses on recent advances in developing lanthanide anticancer agents with an emphasis on lanthanide coordination complexes. These complexes may provide a broader spectrum of antitumor activity. They were compared with classical platinum anticancer drugs. Lanthanides are also of interest because of their therapeutic radioisotopes. The dominant pharmacological applications of lanthanides are as agents in radioimmunotherapy and photodynamic therapy.     

抗肿瘤药与消化道肿瘤化疗患者感染风险的Logistic回归分析

目的：研究抗肿瘤药与消化道恶性肿瘤化疗患者感染发生风险的关系。方法：收集符合条件的消化道肿瘤化疗患者2384例，用Logistic回归分析不同种类化疗药物等因素对患者发生感染的风险性的相关性。结果：年龄、住院天数、费别、烷化剂、金属络合物、其他抗肿瘤药的回归系数分别为0．010，0．147，-0．361，-、930，-0。390，-1．306。结论：年龄和住院天数都对感染发生产生正相关作用，参加医保可以降低感染的发生风险，抗肿瘤抗生素、植物来源抗肿瘤药物、抗代谢抗肿瘤药物比金属络合物抗肿瘤药物、烷化剂和其他类抗肿瘤药物在化疗期间具有较高的感染发生风险比。     

铂类抗肿瘤药的进展与临床评价

目的:探讨铂类抗肿瘤药的临床特点及其研究进展,为临床应用提供参考。方法:通过查阅国内外相关文献,系统地了解铂类抗肿瘤药的临床作用及相关不良反应;并检索近年上市、未获批准及正在进行临床研究的铂类药物,以分析其临床发展趋势。结果与结论:在过去的10年间,药物研发转向注重药物运输靶向介质,这些新药在保留传统铂类化合物的活性的同时,在很大程度上减少了传统铂类药物的不良反应。     

Synthesis and characterization of platinum(II) oxadiazoline complexes and their in vitro antitumor activity in platinum-sensitive and -resistant cancer cell lines

A series of platinum(II) complexes bearing Delta (4)-1,2,4-oxadiazoline ligands have been synthesized and characterized. Their in vitro antitumor activity has been assessed in platinum-sensitive and -resistant human ovarian cancer cell lines (PEO1, PEOCisR, PEOCarboR, and SK-OV3), as well as in colon cancer (SW948) and testicular cancer cell lines (N-TERA). All compounds tested showed potent cytotoxicity in the platinum-sensitive cell lines and retained activity in the cisplatin- and carboplatin-resistant lines, with IC 50 values similar to the parental drug sensitive counterpart. We propose, therefore, that platinum(II) oxadiazoline complexes may possess a novel mechanism of action, which render them active in tumor cells, with resistance to currently used platinum anticancer agents.     

Preparation and in vivo evaluation of liposomal everolimus for lung carcinoma and thyroid carcinoma

Everolimus has demonstrated antitumor efficacy for various cancers as a result of its inhibition of the mammalian target of rapamycin (mTOR) signaling cascade, which activates cell growth and cell proliferation. However, the low water solubility and low bioavailability of everolimus have prevented its clinical development as an anticancer drug. Therefore, to address the unsuitable characteristic of everolimus, we attempted to prepare liposomal everolimus as a viable drug delivery system, and then evaluated the anticancer efficacy of this system against a medullary thyroid carcinoma cell line (TT cells), a breast cancer cell line (MCF-7 cells) and a small lung carcinoma cell line (NCI-H446 cells). The particle size and entrapment efficacy of liposomal everolimus was ca. 80 nm and more than 90%, respectively. Liposomal everolimus showed higher cytotoxicity against NCI-H446 cells compared with TT cells. Against NCI-H446 tumors, significant suppression of the tumor volume was observed in liposomal everolimus-treated mice by intravenous injection, compared with free everolimus-treated mice by intraperitoneal injection, at a dose of 5 mg/kg without body weight loss. This study showed that liposomal everolimus could be a powerful formulation with anticancer efficacy for some cancers.     

铂类抗肿瘤药物及其临床研究进展

铂类药物是一类细胞周期非特异性抗肿瘤药物，抗瘤谱广，DNA是其作用靶点。药物进入体内后，以水合阳离子形式与DNA等生物大分子结合形成共价键。使DNA链局部扭结或解旋，致使DNA复制、转录失败，从而造成肿瘤细胞死亡。以铂为中心的结构变化衍生出了多种新型铂类药物。该文介绍了铂类药物及其临床研究的进展。     

New generation of liposomal drugs for cancer

This review is focused on liposomes as a delivery system for anticancer agents and more specifically on the advantages of using liposomes as drug nanocarrier in cancer chemotherapy. The main advantages of liposomal drugs over the non-encapsulated drugs include: (1) improved pharmacokinetics and drug release, (2) enhanced intracellular penetration, (3) tumor targeting and preventing adverse side effects and (4) ability to include several active ingredients in one complex liposomal drug delivery system (DDS). The review also includes our recent data on advanced liposomal anticancer drug delivery systems. As a conclusion we propose a novel liposomal DDS which includes inhibitors of pump resistance combined in one liposomal drug delivery system with an inhibitor of antiapoptotic cellular defense, an apoptosis inducer (a traditional anticancer drug) and a targeting moiety. The proposed drug delivery system utilizes a novel three tier approach, simultaneously targeting three molecular targets: (1) extracellular receptors or antigen expressed on the surface of plasma membrane of cancer cells in order to direct the whole system specifically to the tumor, preventing adverse side effects on healthy tissues; (2) drug efflux pumps in order to inhibit them and enhance drug retention by cancer cells, increasing intracellular drug accumulation and thereby limiting the need for prescribed high drug doses that cause adverse drug side effects; and (3) intracellular controlling mechanisms of apoptosis in order to suppress cellular antiapoptotic defense.