基于树状大分子材料构建的纳米载药体系用于肿瘤靶向治疗的研究进展

近年来兴起的树状大分子材料的结构可控,且其与细胞膜和各种活性药物分子具有独特的相互作用,因此成为构建纳米载药体系的优良材料,并在肿瘤靶向治疗领域得到了广泛研究。树状大分子作为具有良好生物相容性的纳米分子,可与肿瘤靶向分子偶联,从而将活性药物分子特异性递送到肿瘤组织,如此可最大限度地提高药物的靶向性,并减少其对非靶组织的毒性作用。笔者就近年来基于树状大分子材料构建的纳米载药体系用于肿瘤靶向治疗的研究进展进行综述。     

共载多柔比星与双硫仑Pluronic P123/F127胶束的工艺优化及逆转乳腺癌耐药性的初步研究

目的 制备一种具有固定药物比、可有效改善乳腺癌耐药性并抑制乳腺癌细胞活性的共载多柔比星与双硫仑(disulfiram)普朗尼克(Pluronic)P123/F127胶束.方法 采用四甲偶氮唑蓝比色法(MTT法)筛选最佳协同药物比,薄膜水化法制备形成胶束.利用星点设计?效应面法优化的处方制备胶束,对其进行表征和体外释放评...     

Bispecific antibody complex pre-targeting and targeted delivery of polymer drug conjugates for imaging and therapy in dual human mammary cancer xenografts

Introduction

Doxorubicin, a frontline chemotherapeutic agent, limited by its cardiotoxicity and other tissue toxicities, was conjugated to N-terminal DTPA-modified polyglutamic acid (D-Dox-PGA) to produce polymer pro-drug conjugates. D-Dox-PGA or Tc-99 m labeled DTPA-succinyl-polylysine polymers (DSPL) were targeted to HER2-positive human mammary carcinoma (BT-474) in a double xenografted SCID mouse model also hosting HER2-negative human mammary carcinoma (BT-20).

Methods

After pretargeting with bispecific anti-HER2-affibody-anti-DTPA-Fab complexes (BAAC), anti-DTPA-Fab or only phosphate buffered saline, D-Dox-PGA or Tc-99 m DSPL were administered. Positive therapeutic control mice were injected with Dox alone at maximum tolerated dose (MTD).

Results

Only BT-474 lesions were visualized by gamma imaging with Tc-99 m-DSPL; BT-20 lesions were not. Therapeutic efficacy was equivalent in mice pretargeted with BAAC/targeted with D-Dox-PGA to mice treated only with doxorubicin. There was no total body weight (TBW) loss at three times the doxorubicin equivalent MTD with D-Dox-PGA, whereas mice treated with doxorubicin lost 10 % of TBW at 2 weeks and 16 % after the second MTD injection leading to death of all mice.

Conclusions

Our cancer imaging and pretargeted therapeutic approaches are highly target specific, delivering very high specific activity reagents that may result in the development of a novel theranostic application. HER/2 neu specific affibody-anti-DTPA-Fab bispecific antibody pretargeting of HER2 positive human mammary xenografts enabled exquisite targeting of polymers loaded with radioisotopes for molecular imaging and doxorubicin for effective therapy without the associating non-tumor normal tissue toxicities.     

Evaluation of PLED as a chelating ligand in the preparation of gallium and indium radiopharmaceuticals

The 68Ga and 111In complexes of PLED (N,N'-dipyridoxylethylenediamine-N,N'-diacetic acid) were prepared and their biodistribution determined as a function of time following i.v. injection into rats. The 68Ga and 111In complexes behaved identically and were rapidly cleared from the blood via the kidneys into the urine. Similar rapid urinary excretion was observed in the gamma images obtained from a stump-tailed macaque injected with 111In-PLED. Paper electrophoresis at pH 7.35 showed a single radioactive peak for 111In-PLED which migrated towards the anode. PLED administered by i.p. injection was found to speed the blood pool clearance of previously administered 67Ga-citrate.     

浸涂法荷电微孔滤膜电性能的研究

以流动电位表示荷电微孔滤膜电性能的大小，研究了基膜的结构性能及浸涂工艺对浸涂法荷电微孔滤电性能的影响，为浸涂法荷电微孔滤膜的制备及应用提供了重要依据。     

Brucella epidydimo-orchitis successfully treated with dual oral drug regimen: A case report with differential diagnoses of malignancy and tuberculosis

Brucellosis is a zoonotic disease caused by Brucella spp. When complicated, Brucella may affect any organ system, including the genitourinary system in the form of epidydimo-orchitis. Brucella orchitis is the second most common form of complicated brucellosis. The present case is for an adolescent who is otherwise healthy but presented with right testicular pain. Ultrasound imaging showed heterogeneous enlarged right testis with large heterogeneous mass and central necrosis. α-fetoprotein was normal and β-human choriogonadotropin was negative. Malignancy and tuberculosis were excluded based on histopathology and microbiology of the tissue biopsy, respectively. The history of raw dairy consumption and positive serology for B. melitensis and B. abortus established the diagnosis of Brucella epidydimo-orchitis. Treatment was successful with doxycycline and rifampin for four weeks. In pediatrics, it is important to rule out malignancy and make every attempt to avoid orchidectomy by making necessary investigations and involving infectious diseases consultation.     

Peer review and the process of publishing of adverse drug event reports

Most doctors finish their careers without ever having published a scientific paper. The small percent that do mostly end up writing "case reports". But, unless the report describes some truly extraordinary event, very little ever comes of it, and their publication may do more harm than good. The problem is particularly acute in cases of alleged drug toxicity. Case reports are incomplete, uncontrolled, retrospective, lack operational criteria for identifying when an adverse event has actually occurred, and resemble nothing so much as hearsay evidence, a type of evidence that is prohibited in all courts in all of industrialized societies. When a journal, even a highly respected one, decides to publish hearsay, readers are utterly reliant on the integrity of the journal, the author, and the peer review process; such reliance may not always be warranted. Some recent examples of process failure are provided, as well as some suggestions about possible remedies, including the use of pharmaco-vigilance algorithms.     

胃肠镜洗消过程中溶剂的选择

胃肠镜是一种常见的消化内镜诊疗手段,目前已经成为胃肠疾病临床诊断和治疗的可靠方法之一。由于胃肠镜的构造较为复杂,细菌生物膜易产生并附着于管道壁上,需要对胃肠镜及其管道进行清洗与消毒,选择消毒溶剂非常重要。作者通过对胃肠镜污染以及洗消方法的分析,对胃肠镜洗消过程中溶剂选择问题进行综述。     

Honey with Psilocybe mushrooms: a revival of a very old preparation on the drug market?

In 1996 samples of suspicious honey preparations were confiscated at the Dutch-German border. The labels on the 50 ml jars indicated that the honey contained Stropharia cubensis (better known as Psilocybe cubensis). The jars were filled with honey with a ca. 1 cm layer of fine particles on the top. The particles were collected and subjected to microscopic and chemical analysis. By microscopy mushroom tissue (plectenchym) and spores typical for the genus Psilocybe were identified in all samples. The HPLC analysis with atmospheric pressure mass spectrometry and diode array detection revealed psilocine but psilocybine was not found. The quantitative analysis was very difficult due to the matrix problems. A search showed that the honey with Psilocybe can be purchased in Dutch coffee shops without any limitations although psilocine and psilocybine belong to listed substances according to Dutch law. Received: 1 July 1997 / Received in revised form: 27 August 1997     

聚合物涂层改性对药物洗脱支架植入后血管内膜修复的作用

目的研究雷帕霉素洗脱支架聚合物涂层改性促进血管内皮化及抑制内膜增殖的作用。方法选择32只小型猪,在冠状动脉内随机植入裸支架(BMS)15枚、新型聚合物涂层支架(Polymer)17枚、FireBird2雷帕霉素洗脱支架(SES-FB2)17枚和新型聚合物涂层的雷帕霉素洗脱支架(SES-Plus)15枚,分别于植入后7、28 d取材,用扫描电镜分析内皮化程度,并分别于28、180 d取材,病理分析内膜增生程度。结果扫描电镜分析显示,与SES-FB2组相比,支架植入后7 d和28 d,SES-Plus组内皮覆盖率显著增加(分别为23%±11%比47%±21%和84±21%比100%,P<0.05),而BMS、Polymer和SES-Plus三组之间差异无统计学意义(P>0.05)。病理分析显示,支架植入后28 d和180 d,SES-Plus组和SES-FB2组间的新生内膜面积差异无统计学意义[分别为(2.28±0.84)mm~2比(2.08±0.76)mm~2和(3.19±0.63)mm~2比(3.06±1.33)mm~2,P>0.05]。结论 SES-Plus能有效抑制内膜增生,具有明显的促进内皮化作用。     

盐酸表柔比星长循环热敏冻干脂质体的处方工艺研究与体外释药机制探讨

目的研究盐酸表柔比星长循环热敏冻干脂质体（EPI-LTSL）的处方工艺,并探讨其体外释药机制。方法pH梯度法制备EPI-LTSL并进行冷冻干燥,正交试验优化处方,单因素试验优化工艺。通过观察不同温度下EPI在不同介质中形成沉淀的性状,探索EPI-LTSL的体外释药机制。结果最佳处方及工艺为药脂比1∶10,DPPC/MSPC为82∶8,水化介质为250mmol/L柠檬酸盐（pH4.0）。空白脂质体经15000psi（103MPa）高压均质循环5～6次,100nm聚碳酸酯膜挤压过膜3次;调节脂质体外相pH后,35℃水浴20min载药。冻干脂质体内外相乳糖浓度为9%,采用中速预冻（-65℃）及缓慢的解吸干燥可以制备较好的冻干品。EPI与柠檬酸盐形成的沉淀在42℃可以完全溶解,而在25℃成絮状或片状沉淀。结论制备的EPI-LTSL载药量和包封率较高,粒径较小。冻干脂质体外观平整,内部疏松多孔,色泽鲜亮,复水迅速且粒径变化较小。以柠檬酸盐为水化介质制备的EPI-LTSL,在25℃时包载于脂质体内相的EPI以沉淀稳定存在,而在42℃时可完全溶解释放出来。