丝裂霉素C及其磁性纳米球在小鼠体内相关药动学参数的比较

目的　比较丝裂霉素C磁性纳米球胶体溶液与丝裂霉素C在小鼠体内的血药浓度及相关药动学参数。方法　采用HPLC法 ,测定小鼠经尾静脉注射丝裂霉素C或丝裂霉素C磁性纳米球胶体溶液 (1mg·kg-1·d-1)后 ,在小鼠体内的血药浓度 ,从而得出药—时曲线及相关药动学参数。将血药浓度经SPSS10 .0统计软件进行配对t检验。结果　在小鼠体内 ,丝裂霉素C磁性纳米球胶体溶液的血药浓度明显高于丝裂霉素C ;胶体溶液药—时曲线下面积AUC较丝裂霉素C大 ,表观分布容积Vc较丝裂霉素C小 ,清除率Cl较丝裂霉素C慢 ;胶体溶液和丝裂霉素C在小鼠体内的血药浓度具有显著性差异 (P <0 .0 1)。结论　丝裂霉素C制成磁性纳米球胶体溶液 ,在外加磁场的作用下可延长在血浆中的停留时间 ,降低血管外分布量 ,减慢清除。可望提高药效 ,减少不良反应。     

RP-HPLC法测定5-Fu磁性微球及小鼠各组织中5-Fu的含量

目的:以反相高效液相色谱法测定5-氟尿嘧啶(5-Fu)磁性微球及小鼠各组织中5-Fu的含量,并评价5-Fu磁性微球在小鼠体内的靶向性。方法:15只小鼠尾静脉注射5-Fu及其磁性微球,采用0.5%胃蛋白酶消解磁性微球后经乙酸乙酯2次萃取后以反相高效液相色谱法测定心、肝、肾、脾、肺、脑和肌肉等组织匀浆中5-Fu含量。结果:组织匀浆中5-Fu检测浓度在0.1～25mg·L-1范围内线性关系良好,最低检测浓度为0.1mg·L-1。与注射单一5-Fu对照品比较,小鼠静脉注射5-Fu磁性微球后在肝脏分布明显增加(P<0.05),加入磁性支架和体表磁场的肌肉组织中可见5-Fu分布。结论:本方法适用于测定磁性微球及小鼠各组织中5-Fu的含量;5-Fu磁性微球具有肝靶向性和磁靶向性。     

毛菊苣总倍半萜磁性纳米脂质体在小鼠体内组织分布和靶向效果

目的研究毛菊苣总倍半萜有效部位、脂质体和磁性纳米脂质体在小鼠体内的组织分布和靶向效果。方法采用高效液相色谱法,以山莴苣素的含量为评价指标,研究毛菊苣总倍半萜有效部位溶液组、脂质体溶液组和磁性纳米脂质体溶液组(加磁场)在小鼠体内不同组织器官的药物浓度;并以AUC0-12 h、平均滞留时间(MRT)和靶向效率(TE)、相对靶向效率(RTE)、靶向指数(TI)为指标评价不同剂型的靶向作用。结果尾静脉注射给药10 min后,磁性纳米脂质体组在心、肝、脾、肺、肾脏组织中山莴苣素浓度较有效部位组、脂质体组显著提高;在动物的肝部体外施加磁场,磁性纳米脂质体组肝部位的AUC0-12 h明显高于其他部位,MRT明显的延长,差异具有显著性(P0.01);TE仅在肝部有增加,且TI大于10。结论在外加磁场的作用下,毛菊苣总倍半萜磁性纳米脂质体可改变药物在动物体内的分布,延长药物的作用时间,提高药物在肝部位的特异性和靶向性。     

甲氨蝶呤热敏磁靶向脂质体的制备和靶向性研究

采用正交设计以37℃和43℃释出的游离药物之比为评价指标优化甲氨蝶呤热敏磁靶向脂质体处方。并测定了小鼠尾静脉注射甲氨蝶呤溶液和甲氨蝶呤脂质体后,全血和肌肉中的药物浓度。结果表明,给予甲氨蝶呤脂质体后再外加磁场并置于43℃环境,脂质体靶向效率Te提高6.8倍,相对摄取量Re提高6.5倍。说明本实验制备的脂质体具有很高的靶向性。     

磁性靶向药物的研究概况

磁性药物指将药物和磁性物质共同包裹于聚合物载体中制成的磁性靶向给药系统(MTDDS),利用外加磁场将药物在体内定向移动和定位集中,在磁场区内释放,从而起到靶区局部浓集作用或靶区截流作用.综述磁性靶向药物的组成及分类.对磁性靶向给药系统现存问题进行总结并对前景进行展望.     

阿霉素磁靶向药物制剂研究进展

磁靶向给药系统在肿瘤治疗方面已越来越受到关注,其先将药物负载到磁性聚合物微球上,然后通过外加磁场作用使载药微球定位至病灶部位,药物通过脱附作用或载体降解等途径在病灶部位释放产生疗效。该文在磁靶向制剂的发展背景基础上,探讨阿霉素磁性靶向制剂的发展及研究概况,并对其发展前景进行展望。     

丝裂霉素C磁性纳米微球的制备

目的:以丝裂霉素C为药物模型,研究磁性纳米抗肿瘤药物的制备工艺及方法。方法:采用正交设计优化工艺并筛选,以纳米级Fe_3O_4为磁性核心,人血清白蛋白为膜材,利用乳液固化法制备包载丝裂霉素C 的磁性纳米微球,并借助透射、扫描电镜观察微球形态,通过激光粒度分析仪作粒度分析,利用高效液相色谱(HPLC)测量载药量及包封率,以磁性测试仪进行体外磁响应性测定。结果:该优化的磁性纳米微球在电镜下呈表面光滑的核壳样球型微粒,平均粒径为217.7nm,微球载药量为7.89%,包封率为90.5%,体外饱和磁化强度为21.85emu·g~(-1)。结论:磁性纳米载药微球为肿瘤的主动靶向治疗提供了一种可能的新剂型,有较好的临床应用前景。     

靶向输运磁性载药颗粒的研究进展

介绍了目前磁性药物靶向治疗的进展,主要包括纳米磁性药物载体的性质,磁靶向系统的磁场装置,靶向性研究,动力学模拟,以及对磁性靶向治疗的前景与展望。     

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。     

齐墩果酸聚氰基丙烯酸正丁酯纳米囊在小鼠体内的肝靶向研究

目的:研究齐墩果酸聚氰基丙烯酸正丁酯纳米囊(OA-PBCA-NC)在小鼠体内的肝靶向性。方法:小鼠尾静脉注射OA-PBCA-NC试验组及齐墩果酸(OA)对照组,HPLC法测定小鼠心、肝、脾、肺、肾各脏器及血浆中OA的含量,比较两组体内分布特点,并进行靶向性评价。结果:秩和检验结果表明静脉注射OA-PBCA-NC试验组与OA对照组比较,其在肝脏的分布差异有显著性,OA-PBCA-NC静脉注射给药后能显著增加OA在肝脏的分布。试验组各肝靶向指标结果均优于对照组。结论:OA-PBCA-NC能增加OA的肝靶向性。     

丝裂霉素C磁性纳米粒Ⅱ.大鼠体内的药动学和靶向性

评价了丝裂霉素C磁性纳米粒（1-MNP）在大鼠体内的约动学和靶向性。采用HPLC法测定大鼠肝、肾和血浆中的约物浓度。采用约物的靶向效率（DTE）、相对靶向效率（RTE）、靶向性指数（DTI）和相对靶向指数（RTI）评价了磁场作用下1-MNP在大鼠体内的靶向性。结果表明，1-MNP在磁场作用下能改变大鼠体内的药物分布，并显著增大靶器官中的药物浓度。     

羟基喜树碱纳米粒在大鼠体内的药动学、组织分布及靶向性研 究

目的:研究羟基喜树碱纳米粒在大鼠体内的药动学及组织分布特征,并探讨其靶向性.方法:将雄性SD大鼠随机分为两组,每组6只,分别单剂量尾静脉注射羟基喜树碱纳米粒和市售羟喜树碱注射液(4 mg/kg,以羟基喜树碱计),在给药后5、30、60、120、240、360、480、600、720 min时于眼底静脉丛取血500μL,...     

卡铂碳包铁纳米笼壳聚糖微球在大鼠体内的分布和药代动力学研究

目的观察卡铂碳包铁纳米笼壳聚糖微球(carbopla-tin-Fe@C-loaded chitosan nanoparticles,C-Fe@C-CN)经肝动脉注射后结合磁场在正常大鼠体内靶向分布和药动学参数。方法将C-Fe@C-CN用99Tc标记后,观察大鼠体内放射性核素分布情况。建立生物样品中卡铂的石墨炉原子分光光度计测定法,并测定大鼠给药后的血浆及组织中药物浓度。结果核素照片显示99Tc标记的C-Fe@C-CN浓集于靶区肝,其它脏器分布很少。经肝动脉注射C-Fe@C-CN在施加磁场的左肝叶各时间段组织中卡铂浓度较卡铂针剂明显增加(P<0.01),非靶向区组织中药物浓度则明显降低(P<0.01)。C-Fe@C-CN的血浆药-时曲线下面积和平均驻留时间分别是卡铂针剂的3和2.6倍,说明C-Fe@C-CN延长了卡铂在血中的存留时间,增大了血药浓度-时间曲线下面积。结论C-Fe@C-CN在外加磁场的作用下具有很好的肝靶向性及一定的缓释和减毒效果。     

丝裂霉素C在小梁切除术治疗青光眼中的应用

目的评价丝裂霉素C在复合式小梁切除术治疗青光眼中的作用。方法选择2008年1月-2010年1月在我院眼科行MMC联合小梁切除术36例45眼和小梁切除术33例40眼的两组患者,年龄和性别基本匹配,进行回顾性比较分析。结果 MMC组出院时成功率97.8%,术后3、6、12个月成功率分别为93.3%、90.5%、82.5%。对照组出院时成功率95.0%,术后3、6、12个月成功率分别为71.8%、69.2%、67.6%。经过χ2检验,两组成功率比较差异有统计学意义(P<0.05)。结论小梁切除术联合丝裂霉素C能安全、有效地治疗青光眼。     

Approaches to reducing toxicity of parenteral anticancer drug formulations using cyclodextrins

Mitomycin C (MMC) is a clinically useful anticancer drug which can cause severe dermatological problems upon injection. It can cause delayed erythema and/or ulceration occurring either at or distant from the injection site for weeks or even months after administration. In an attempt to reduce the skin necrosis, complexation of MMC with cyclodextrins was studied in order to help increase patient compliance and acceptance. The complexation of MMC with 2-Hydroxypropylbetacyclodextrin (HPBCD) in the presence and absence of mannitol was studied and it was found that the mannitol present in the commercial formulation caused an increase in the binding of MMC to HPBCD. Isotonicity adjustment of hypotonic MMC formulations by the addition of normal saline did not change the degree of complexation with MMC. The complexed formulations were then tested to determine their antitumor efficacy using the B-16 melanoma cell model. No difference in antitumor activity between the complexed and uncomplexed MMC formulations was observed. Different MMC formulations were tested for their potential to produce skin irritation and/or toxicity using intradermal injections in a BALB/c mouse model in order to find the most suitable formulation. The skin ulceration studies indicated that there were no significant differences between the isotonic MMC solution and isotonic formulations of MMC complexed with HPBCD.     

In vivo characterization of indomethacin magnetic polymethyl methacrylate nanoparticles

The in vivo magnet responsiveness and kinetics of distribution of indomethacin entrapped in a magnetic and plain carrier were characterized by rat tail model and periodic monitoring of drug concentration in various visceral organs after intraarterial and intravenous administration respectively. Up to 60 min post injection time 60-fold higher concentrations could be achieved in tail target segment which resulted in considerably reduced drug concentration in other organs as evinced by data from control rats. Following normal administration (no magnetic field applied) the drug concentration was higher in the liver and spleen where endocytosis and phagocytosis occur. The magnetic nanoparticle of indomethacin holds promise for selective targeting under magnetic field of 8000 Oe strength.     

In Vivo Characterization of Indomethacin Magnetic Polymethyl Methacrylate Nanoparticles

Abstract

The in vivo magnet responsiveness and kinetics of distribution of indomethacin entrapped in a magnetic and plain carrier were characterized by rat tail model and periodic monitoring of drug concentration in various visceral organs after intraarterial and intravenous administration respectively. Up to 60 min post injection time 60-fold higher concentrations could be achieved in tail target segment which resulted in considerably reduced drug concentration in other organs as evinced by data from control rats. Following normal administration (no magnetic field applied) the drug concentration was higher in the liver and spleen where cndocytosis and phagocytosis occur. The magnetic nanoparticle of indomethacin holds promise for selective targeting under magnetic field of 8000 Oe strength.     

Multifunctional magnetic nanoparticles for targeted delivery

A major problem associated with drug therapy is the inability to deliver pharmaceuticals to a specific site of the body without causing nonspecific toxicity. Development of magnetic nanoparticles and techniques for their safe transport and concentration in specific sites in the body would constitute a powerful tool for gene/drug therapy in vivo. Furthermore, drug delivery in vitro could improve further if the drugs were modified with antibodies, proteins, or ligands. For in vivo experiments, magnetic nanoparticles were conjugated with plasmid DNA expressing enhanced green fluorescent protein (EGFP) and then coated with chitosan. These particles were injected into mice through the tail vein and directed to the heart and kidneys by means of external magnets of 25 gauss or 2kA–kA/m. These particles were concentrated in the lungs, heart, and kidneys of mice, and the expression of EGFP in these sites were monitored. The expression of EGFP in specific locations was visualized by whole-body fluorescent imaging, and the concentration of these particles in the designated body locations was confirmed by transmission electron microscopy. In another model system, we used atrial natriuretic peptide and carcinoembryonic antigen antibodies coupled to the chitosan-coated magnetic nanoparticles to target cells in vitro. The present work demonstrates that a simple external magnetic field is all that is necessary to target a drug to a specific site inside the body without the need to functionalize the nanoparticles. However, the option to use magnetic targeting with external magnets on functionalized nanoparticles could prove as a more efficient means of drug delivery.From the Clinical EditorThis paper addresses targeted drug delivery with magnetic nanoparticles. The authors demonstrate that a simple external magnetic field is sufficient to target a drug to specific sites in the body without the need for functionalized nanoparticles, at least in selected organs and diseases.     

In vitro and in vivo evaluation of targeting efficiency of Adriamycin hydrochloride magnetic microspheres

The objective of this study was to prepare magnetic microspheres as a targeting drug delivery system and to specifically evaluate its targeting efficiency. The magnetic microspheres were prepared by emulsion cross-linking techniques. Targeting efficiency was specifically investigated by experiments of biodistribution on rats and histological study. Adriamycin hydrochloride (ADR)-loaded magnetic microspheres were successfully prepared with the mean diameter of 3.853 μm (± 1.484 μm), and had its speciality of superparamagnetism. The results of the targeting efficiency study showed that application of the external magnetic field significantly increased the ADR concentration from 40.28 μg/ml to 100.70 μg/ml at 10?min, 36.99 μg/ml to 91.16 μg/ml at 60?min, and 13.71 μg/ml to 28.30 μg/ml at 180?min in liver as the targeting tissue. The relative uptake efficiencies in liver by injection treatment of ADR magnetic microspheres with external magnetic field were 3.87, 5.59, and 3.34 at 10?min, 60?min, and 180?min after administration, respectively. In conclusion, distinguished targeting efficiency was displayed, which indicated that the magnetic microspheres could be applied as a novel targeting drug delivery system.