阿霉素磁性明胶微球的研究

报告了阿霉素磁性明胶微球（Ａｄｒ－ＭＧ－ｍｓ）的制备与性质，研究了超细氧化铁粒子的合成和磁性明胶微球（ＭＧ－ｍｓ）在狗体内的栓塞效果。阿霉素磁性明胶微球由２％阿霉素（Ａｄｒ）、６８％明胶和３０％的磁铁粒子组成，微球的平均粒径为２２μｍ。在体外实验中，药物释放速度证明微球有缓释的性质。磁铁粒子的平均粒径约为１０ｎｍ，磁性明胶微球与￣（９９ｍ）Ｔｃ标记磁性明胶微球通过导管分别输入狗的肝动脉内进行栓塞，照相和血管造影显示在未加外磁场时磁性明胶微球在左右肝叶分布几乎相等，而在１２００高斯的外磁场作用下，靶部位肝左叶的微球分布是肝右叶的２．２５倍，而甲状腺、脑、心脏的微球很微量，结果表明磁性明胶微球在外磁场作用下是一个很好的治疗肝癌的栓塞剂。     

磁性微球的磁响应性及狗肾动脉栓塞实验研究

研究了磁性明胶微球(MG-ms)的磁响应性及狗肾动脉栓塞效果。磁响应性实验表明,介质流速越慢,磁场强度越大,磁性微球中磁铁粒子含量越高,越容易定位磁性微球。狗肾动脉灌注10～30um磁性微球,血管造影和病理切片结果表明:磁性微球在外磁场作用下可以进一步栓塞至肾小球、肾脏的微细动脉,而且栓塞均匀、完全,而不加磁场时栓塞不完全。这些结果提示磁性明胶微球可以作为治疗肾癌的栓塞剂,将有利于增强化疗效果、减少毒副反应。     

亚甲蓝磁性明胶微球的制备及特性试验

目的：制备亚甲蓝磁性明胶微球并检测其特性。方法：采用乳化-交联法制备亚甲蓝磁性明胶微球，高倍镜观察微球粒径大小及形态，紫外-可见分光光度法检测微球中亚甲蓝的含量及其体外释放规律。结果：亚甲蓝磁性明胶微球粒径38—50μm，在4000GS的磁场下动作距离为70—80mm，载药量为9．8％，180min体外累积释放量为90％。结论：亚甲蓝磁性明胶微球是一种新剂型，制备工艺简便，具有较好的磁响应性和一定缓释性。     

阿霉素磁性明胶微球的制备及特性研究

采用乳化－交联技术制备阿霉素磁性明胶微球，并用荧光分光光度法测定磁性微球中的药量。用原子吸收分光光度法测定磁性微球中磁铁粒子的含量。用振动样品磁强计测定磁性微球的磁性。同时测定了微球粒径大小与分布。     

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。     

阿霉素聚乳酸微球的含量测定

阿霉素（ADM）的含量测定方法国内已报道有很多种,如荧光分光光度法测定明胶磁性微球中阿霉素的含量,紫外分光光度法测定阿霉素磁性明胶微球的含量,反相高效液相色谱一荧光检测法测定阿霉素磁性豪微球等啊。本实验用溶解法将聚乳酸的网状结构破坏后,再采用紫外一可见分光光度法测定聚乳酸微球中阿霉素的含量。该方法快速、准确、结果满意。     

低剂量阿霉素磁性微球的体内动力学

作者将低剂量阿霉素(0.05mg/kg)包封在磁性微球中,以100倍高剂量的游离型阿霉素静脉注射(5mg/kg)作对照,用小白鼠尾为靶部位进行体内动力学研究。实验表明,在给药后60分钟,低剂量阿霉素磁性微球在靶部位保留时间约为游离型阿霉素二倍的浓度。以~(125)I标记微球,测定载体的体内分布。将鼠尾分为四段,第三段为靶部位暴露于强度为8000奥斯特(Oe)的磁场、梯度±4000 Oe。在鼠腹侧尾动脉注射微球5～60分钟内,肝、肺、脾仅有少量分布;心、肾和鼠尾1,     

核素标记叶酸偶联白蛋白纳米微球对人卵巢癌细胞生长的影响

目的观察核素标记叶酸靶向白蛋白纳米微球对人卵巢癌细胞生长的影响。方法将体外培养的SKOV3人卵巢癌细胞分为八组:阴性对照组(只加RPMI-1640培养液),单纯化疗组(叶酸偶联载药白蛋白磁性纳米微球,不加磁场),单纯放疗组[188铼(188 Re)标记的叶酸偶联白蛋白磁性纳米微球,不加磁场],单纯热疗组(叶酸偶联白蛋白磁性纳米微球,加磁场),化疗联合放疗组(188 Re标记的叶酸偶联载药白蛋白磁性纳米微球,不加磁场),化疗联合热疗组(叶酸偶联载药白蛋白磁性纳米微球,加磁场),放疗联合热疗组(188 Re标记的叶酸偶联白蛋白磁性纳米微球,加磁场)和热疗、化疗、放疗联合治疗组(联合治疗组,188 Re标记的叶酸偶联载药白蛋白磁性纳米微球,加磁场)。48h后MTT方法测定各组细胞增殖率,流式细胞术测定细胞凋亡率。结果阴性对照组对卵巢癌细胞增殖的抑制作用弱于其他各组,联合治疗组强于其他各组(P<0.05)。单纯热疗组、化疗联合放疗组、化疗联合热疗组、放疗联合热疗组和联合治疗组中细胞周期G1期前出现明显的亚二倍体凋亡峰;阴性对照组、单纯热疗组、化疗联合放疗组、化疗联合热疗组、放疗联合热疗组和联合治疗组的细胞凋亡率分别为0.08%、7.56%、17.14%、21.64%、33.94%和57.16%。结论磁感应热疗、化疗、核素靶向放疗的联合作用能有效抑制人卵巢癌细胞的生长。     

磁性抗癌药物载体的研制

磁性微球抗癌药物载体在体外磁场的引导下,能定向移动和固定在肿瘤部位,本文采用单凝聚冻缩法制备出了直径为3～15μm 的磁性微球载体。载体中抗癌药含量为4.5～30%.     

丝裂霉素C-磁性纳米球在小鼠体内的分布

目的研究丝裂霉素C-磁性纳米球胶体溶液剂和丝裂霉素C生理盐水溶液中丝裂霉素C(MMC)在小鼠体内的分布。方法建立生物样品中MMC的HPLC测定法,并测定了小鼠给药后的血浆及组织中药物浓度。结果小鼠尾静脉注射(1 mg.kg-1)丝裂霉素C-磁性纳米球胶体溶液剂,在外加磁场的引导下,30 m in即有82.72%的药物浓集于肝脏,是MMC生理盐水溶液34.83%分布量的2.37倍,在心、肾中的分布较MMC生理盐水溶液低。与尾静脉注射非磁丝裂霉素C纳米球胶体溶液剂的结果比较,外加磁场与磁纳米球的相互作用可大大地提高磁纳米球对肝脏的靶向率。与不施加磁场注射同剂量磁性纳米球的结果比较,说明外磁场可以非常有效地提高磁性纳米球在靶部位的浓集。结论丝裂霉素C制成磁性纳米球,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。     

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。     

99mTc标记的大肠癌单克隆抗体在小鼠体内分布特点的研究

目的：研究^99m-Tc标记的大肠癌单克隆抗体(^99mTc—ACCmAb)在正常小鼠和荷瘤裸鼠体内的分布及在荷瘤裸鼠体内SPECT成像的研究。方法：将^99m-Tc和^99mTc—ACCmAb分别注射入正常小鼠、荷L010-16人结肠癌裸鼠，按不同时间点采取小鼠的脏器进行同位素放射性活度的测定；并在不同时间测定荷L010-16人结肠癌裸鼠注射^99mTc—ACCmAb的SPECT显像。结果：注射^99mTc后正常小鼠体内6h5min血液中的放射性活度与30min相比下降了76．6％，是30min的23．4％；肝脏中6h5min的放射性活度为30min的27．2％，下降了72．8％。尾静脉注射^99mTc-ACCmAb的正常小鼠，6h5min在血液中的放射性活度与30min血液中的放射性活度比较下降了68．4％，是30min的31．6％，24h为6h5min的6．1％，下降了93．9％；荷瘤裸鼠体内^99mTc-ACCmAb在24h血液中的放射性活度是6h5min的2．1％，下降了97．9％。SPECT显像结果表明，虽然在注射^99mTc-ACCmAb20h血液与肿瘤的比值为最高，但在24h的成像结果仍然好于其他的时间点。结论：^99m-Tc标记的大肠癌单克隆抗体可特异性浓聚于荷L010-16人结肠癌裸鼠模型中，可能成为大肠癌根除手术中使用的手术导向体内诊断用药，保证手术切除肿瘤的彻底性。     

Labeling efficiency and biodistribution of Technetium-99m labeled nanoparticles: interference by colloidal tin oxide particles

The interference of colloidal tin oxides on the biodistribution of (99m)Technetium radiolabeled chitosan nanoparticles has been overcome by using sodium borohydride instead of commonly used stannous salts as reducing agent for the reduction of (99m)Tc (VII) to lower valency states. Biodistribution of radiolabeled chitosan nanoparticles prepared by using stannous chloride method revealed localization of the radioactivity mainly in the liver and spleen while that of radiolabeled chitosan nanoparticles prepared by using sodium borohydride method manifested the presence of radioactivity in blood up to an extent of 10% even after 2 h. Interestingly, the reduction of radioactivity in the latter case with the progress of time was not manifested through an increase in activity in the liver. Rather, a time dependent increased accumulation of radioactive materials was observed in the stomach. From the results it has been concluded that the biodistribution is strongly influenced by the presence of colloidal particles of tin oxides and (99m)Tc labeled chitosan nanoparticles are RES evading and long circulating in blood when Tc (VII) is reduced by sodium borohydride and not by stannous chloride during radiolabeling process.     

The challenges of quantitative measurement of lung deposition using 99mTc-DTPA from delivery systems with very different delivery times.

In quantifying aerosol delivery, the drug is often mixed with a radiolabel such as (99m)Tc-DTPA whose deposition is used as a proxy for the drug. (99m)Tc-DTPA deposited in the lung is cleared by a combination of absorption into the pulmonary circulation and mucociliary clearance. If administration is not instantaneous, the image will not include that clearance during administration, a problem raised if comparing devices with different administration times. However, if rates of clearance are measured, it will be possible to "correct" the initial image for the clearance that occurred during administration and before counting. Five adult males inhaled a 5-mL solution containing (99m)Tc-DTPA from a breath enhanced jet nebulizer (LC Plus)over the course of 10 min and a 1.25-mL solution from a vibrating membrane device (eFlow), which was delivered in 2.5 min. Quality assurance was the radioactivity count balance (RCB) defined as the difference in the total radioactivity pre-nebulization less post, divided by pre, and expressed as a percentage. Attenuation calculations used a (57)Co flood source (Macey and Marshall). The "correction" for the clearance of (99m)Tc-DTPA was 0.91 +/- 0.04 (mean +/- SD) for the LC Plus) and 0.96 +/- 0.02 for the eFlow). RCB was -0.6 +/- 3.5% for the LC Plus and -4.7 +/- 6.4% for the eFlow, implying acceptable accuracy. For the LC Plus, lung deposition was 15.9(13.4, 18.4)% (mean and 95% CI) of the charge dose, and for the eFlow it was 32.0(29.0, 35.0)%. This technique gave an acceptable level of accuracy for quantitative planar imaging and allowed the comparison of delivery from devices with very different rates of delivery.     

磁场治疗癫痫的实验研究

利用家兔癫痫模型，把恒磁片埋入其头部有抑制癫痫发作频率的作用。在此动物实验的基础上，采用了磁发带和磁埋藏的方法，对人类癫痫患者在减少服用原来抗癫痫药物的情况下，进行追踪治疗3～12个月。结果：近期有效率为65．6％，远期有效率为66．7％；磁发带组总有效率为63．6％，磁埋藏组总有效率为70％。在给磁场治疗前后，部分患者还测定了免疫功能和头发微量元素，自身对照均未见明显影响。     

Effect of mitomycin-C on the bioavailability of the radiopharmaceutical (99m)technetium-phytic acid in mice: a model to evaluate the toxicological effect of a chemical drug.

The many desirable characteristics of technetium-99m ((99m)Tc) have stimulated the development of labelling techniques for different molecular and cellular structures. It is generally accepted that a variety of factors can alter the biodistribution of radiopharmaceuticals and one such factor is drug therapy. Because patients on chemotherapeutic treatment receive a radiopharmaceutical in a nuclear medicine procedure, we have studied in Balb/c mice the effect of mitomycin-C on the biodistribution of the radiopharmaceutical (99m)Tc-phytic acid ((99m)Tc-PHY) used in hepatic scintigraphy. Mitomycin-C is an antineoplastic agent obtained from Streptomyces caesptosus and is used on the treatment of disseminated adenocarcinoma of the stomach or pancreas. Three doses of mitomycin-C were administered via the ocular plexus into Balb/c mice. One hour after the last dose, (99m)Tc-PHY was administered and the animals were sacrificed. The organs were isolated, the radioactivity was determined in a well counter and the percentages of radioactivity in the organs were calculated. The results have shown that the percentage radioactivity has been increased in stomach, spleen, lung, thyroid and bone, decreased in pancreas and thymus and not altered in ovary, uterus, kidney, heart, liver and brain. The changes in the distribution of (99m)Tc-PHY may be the result of metabolic processes and/or therapeutic actions produced by the administration of mitomycin-C.     

Dose variance associated with calibration and administration of radiopharmaceuticals.

Variation in the amounts of radioactivity that is associated with dose calibration and administration of gamma-emitting radioactive drugs was studied. Health systems use radionuclide dose calibrators when they need to assay drugs for radioactivity. However, the radioactive drugs commonly used for therapeutic or diagnostic purposes are compounded and assayed in or administered from containers that differ from those containing the standard reference materials (SRMs). SRMs for four radionuclides--technetium 99m, indium 111, thallium 201, and iodine 131--were drawn up into vials and syringe-needle assemblies of volumes and sizes represented in clinical practice. In each sample, the amount of radioactivity was calculated and compared with values obtained from three dose calibrators. In addition, over a four-month period, 101 samples of technetium Tc 99m medronate injection with a desired activity of 20 mCi were prepared in syringes; the radioactive dose in each syringe was calibrated for administration to a patient at a specific time that day. The amounts of radioactivity at the time of preparation and the time of administration, the amount remaining in the syringe and needle after administration, and the amount reported as administered were recorded. Measurement with the dose calibrators of the SRMs in containers supplied by the National Institute of Standards and Technology showed radioactivity within 10% of the labeled amount, the percentage of variation regulations allow. Measurements of the SRMs in syringe-needle assemblies were within 10% for technetium 99m and thallium 201, 9-16% for iodine 131, and 15-26% for indium 111. The individual doses of technetium 99m medronate injection were, on average, administered on time, but doses were administered up to 75 minutes before and 107 minutes after the calibration time. The mean +/- S.D. amount administered was 19.0 +/- 1.34 mCi. The mean +/- S.D. amount reported administered was 20 +/- 0.24 mCi. How radiopharmaceuticals were dose calibrated and administered influenced the actual dose available to patients.     

Site of deposition and absorption of an inhaled hydrophilic solute

AIMS: To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. METHODS: Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid ((99m)Tc-DTPA) in an open and crossover fashion. Pulmonary doses were administered as nebulized large and fine droplet-sized aerosols by Pari and UltraVent nebulizers at fairly rapid and slow inhalation flows, respectively. Plasma concentration-time profiles and 24 h urinary excretion of radioactivity were determined. One dose of (99m)Tc-labelled Nanocoll, as a marker of mucociliary clearance (MCC), was also administered by Pari for similar lung deposition as the (99m)Tc-DTPA and followed by repeated chest gamma-imaging. RESULTS: Intrapulmonary deposition patterns of (99m)Tc-DTPA differed significantly (the mean ratio of penetration index (Pari : UltraVent) was 76% with 95% CI 63%, 91%). However, no differences in rate or extent of (99m)Tc-DTPA absorption were detected. Mean absorption time was 1.8 h (mean difference (Pari-UltraVent): -0.1 h with 95% CI -0.6 h, 0.3 h) and the bioavailability was 70% (mean ratio (Pari : UltraVent): 101% with 95% CI 90%, 115%). The pulmonary elimination half-life of (99m)Tc-Nanocoll (8 h and 45 min) was significantly longer than that of (99m)Tc-DTPA (less than 2 h). The oral bioavailability of (99m)Tc-DTPA was estimated to be 3.1%. CONCLUSIONS: The main elimination pathway of the inhaled hydrophilic solute (99m)Tc-DTPA from the lungs is trans-epithelial absorption. Despite different intrapulmonary radioaerosol deposition patterns, as verified by gamma scintigraphy, no differences in (99m)Tc-DTPA absorption kinetics or bioavailability were detected.     

Absorption and mass balance of piperonyl butoxide following an 8-h dermal exposure in human volunteers.

Dermal absorption, metabolism and excretion of piperonyl butoxide (PBO) was studied using 14C-PBO either by itself as a 3% (w/w) solution in isopropyl alcohol or as a 4% (w/w) solution in an aqueous end-use formulation. Each of these two formulations were tested on four young, healthy male volunteers, using a single topical application on the ventral forearm under non-occlusive conditions for an 8-h period. The application sites were thoroughly cleaned with cotton swabs moistened with isopropyl alcohol, then rinsed with isopropyl alcohol. Blood from the ipsilateral and contralateral arms, urine and feces were collected at selected intervals during the 8-h application and through a 120-h post-application period. The application area was also tape-stripped to determine if any of the test material accumulated in the stratum corneum. These samples provided data which permitted insight into the kinetics of penetration and elimination processes of PBO. The absorption of PBO either by itself or formulated was very poor, as demonstrated by the radioactivity excreted in the urine, and radioactivity in the ipsilateral plasma. When dosed by itself, approximately 1.78% of the dose was excreted in the urine. In contrast, only 0.47% of the formulated PBO was excreted in the urine. Trace radioactivity was detected in the feces from both formulations. The absorbed radioactivity was rapidly eliminated in the urine. There was no evidence of accumulation of PBO in the skin as evidenced by low amounts of radioactivity in the tape-strippings. The majority of the applied radioactivity was recovered from the skin surface. Total recovery of the applied radioactivity was 100.86 and 104.22% for PBO and the formulated product respectively. Absorbed PBO was completely metabolized to at least three major metabolites prior to its excretion in the urine. The three metabolites represented over 70% of the excreted radioactivity for PBO. The HPLC retention times for these metabolites are different than that seen in rats. The structures of these metabolites have not been elucidated.