Improved solubility and in vitro dissolution of Ibuprofen from poloxamer gel using eutectic mixture with menthol

To improve the solubility and in vitro dissolution of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6, followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without poloxamer and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.     

^188Re标记单克隆抗体BAC5及对鼻咽癌细胞的抑制实验研究

目的 探讨放射性核素^188Re标记抗鼻咽癌（NPC）单抗BAC5的方法及^188Re-BAC5对鼻咽癌进行免疫导向治疗的可行性。方法 ^188Re-BAC5的制备采用直接标记法，采用MTT法观察^188Re-BAC5对体外单层培养的鼻咽癌细胞（CNE－2）的抑制作用，对照组为^188Re-BSA、^188ReO4^-。结果 ^188Re-BAC5的标记率在80％以上，MTT法结果表明^188Re-BAC5组的抑瘤率比对照组明显提高（P＜0．05）。结论 提示^188Re-BAC5有可能在对人鼻咽癌的放免导向治疗中起到良好的作用。     

188Re-CEA人/鼠嵌合抗体在裸鼠人结肠癌模型中的定位研究

目的 :评价1 88Re标记抗CEA人 鼠嵌合抗体在人结肠癌裸鼠模型中的肿瘤靶向性。方法 :于裸鼠尾静脉注入1 88Re CEA人 鼠嵌合抗体后 2 4、4 8、72、96h分别测定荷瘤小鼠体内组织放射性分布 ,于不同时相分别对尾静脉注射1 88Re CEA嵌合抗体及1 88Re C5 0鼠单抗的裸鼠行放免显像。结果 :1 88Re CEA嵌合抗体注射后 9 5h ,肿瘤部位开始有放射性浓聚。以后随时间的增加 ,肿瘤部位放射性持续存在并维持较高水平 ,而周围组织放射性逐渐清除。1 88Re CEA人 鼠嵌合抗体与1 88Re C5 0抗体一样在肿瘤中有很高的摄取。肿瘤组织在注射1 88Re CEA人 鼠嵌合抗体 2 4h后 ,摄取放射性占总注入量的百分比为11 0 5 % ,随时间的延长稍有增加。 96h时所有脏器T NT比均大于 2 0。结论 :1 88Re CEA人 鼠嵌合抗体可特异地浓聚于结肠癌组织 ,有望用于临床诊断和治疗。     

β射线诱导人肝癌细胞凋亡

0　引言　凋亡或细胞程序性死亡是一种不同于细胞坏死的死亡方式 ,是在基因控制下的有序死亡 ,是一个主动性自杀过程 ,常伴有特征性形态学和生化变化 .临床上放射线治疗肿瘤主要应用射线诱导细胞凋亡这一机制 .1 88Re发射 2 110Ke V的 β射线 ,15 5 Ke Vγ射线 ,半衰期 17h,具有良好的核物理性质 .国外 1 88Re的研究主要在 1 88Re标记单克隆抗体对肿瘤的放射免疫治疗 ,并显示具有一定的疗效 ,而国内关于 1 88Re的研究较少 ,经文献检索未见有关于 1 88Re诱导细胞凋亡的报道 .本实验旨在研究 1 88Re-β射线诱导人肝癌细胞系 h HCC(human…     

Dose evaluation and measurement of the Re liquid-filled balloon in intravascular brachytherapy

We compared the Monte Carlo evaluation and GafChromic MD-55 film experimental measurement of ¹⁸⁸Re liquid-filled balloons in intravascular brachytherapy using two phantoms of 6 mm vascular diameter, a phantom of 4 mm vascular diameter and a phantom of 3 mm vascular diameter. A dose-evaluation interface program was developed and was shown to be capable of quickly providing information such as the necessary ¹⁸⁸Re source irradiation time to deliver a prescribed dose.     

The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain

Purpose The surface bone-seeking radiopharmaceuticals rhenium-188-HEDP (¹⁸⁸Re-HEDP) and samarium-153-EDTMP (¹⁵³Sm-EDTMP) were investigated to determine the efficacy and toxicity in pain palliation in bone metastases.Method The effect of treatment with ¹⁸⁸Re-HEDP and ¹⁵³Sm-EDTMP on pain symptoms, life quality, and bone marrow function were obtained in 46 patients with prostate and breast cancer. There were 31 patients treated with ¹⁸⁸Re-HEDP (3194±387 MBq) and 15 patients with ¹⁵³Sm-EDTMP (2940±545 MBq). The ¹⁸⁸Re-HEDP group included 6 patients and 25 patients, and the ¹⁵³Sm-EDTMP group 6 patients and 9 patients with breast and prostate cancer, respectively. All patients had an interview using standardized sets of questions before and after therapy for 12 weeks. Blood counts were taken weekly for 6 weeks and after 12 weeks.Results After treatment with ¹⁸⁸Re-HEDP, 77% of patients reported pain relief and 73% after ¹⁵³Sm-EDTMP. Sixteen percent of the patients treated with ¹⁸⁸Re-HEDP and 13% of those given ¹⁵³Sm-EDTMP could discontinue their analgesics and were pain free. Patients described an improvement on the Karnofsky performance scale from 73±7 to 85±8% 12 weeks after ¹⁸⁸Re-HEDP (p<0.05) and from 68±9 to 74±9% after ¹⁵³Sm-EDTMP (p=0.217). Only 3 patients post-¹⁸⁸Re-HEDP and 2 patients post-¹⁵³Sm-EDTMP showed a thrombocytopenia below 100×10³/µl. The maximum nadir of platelet and leukocyte counts were observed between the second to fourth week after treatment in both and was reversible within 12 weeks. There were no significant differences in pain palliation, Karnofsky performance scale and bone marrow toxicity between the lower beta energy ¹⁵³Sm-EDTMP and the higher beta energy ¹⁸⁸Re-HEDP (p=0.098–0.442).Conclusion Both radiopharmaceuticals were effective in pain palliation, without induction of severe side effects or significant differences in therapeutic efficacy or toxicity.     

Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells

Beta-irradiation used for systemic radioimmunotherapy (RIT) is a promising treatment approach for high-risk leukaemia and lymphoma. In bone marrow-selective radioimmunotherapy, beta-irradiation is applied using iodine-131, yttrium-90 or rhenium-188 labelled radioimmunoconjugates. However, the mechanisms by which beta-irradiation induces cell death are not understood at the molecular level. Here, we report that beta-irradiation induced apoptosis and activated apoptosis pathways in leukaemia cells depending on doses, time points and dose rates. After beta-irradiation, upregulation of CD95 ligand and CD95 receptor was detected and activation of caspases resulting in apoptosis was found. These effects were completely blocked by the broad-range caspase inhibitor zVAD-fmk. In addition, irradiation-mediated mitochondrial damage resulted in perturbation of mitochondrial membrane potential, caspase-9 activation and cytochrome c release. Bax, a death-promoting protein, was upregulated and Bcl-x_L, a death-inhibiting protein, was downregulated. We also found higher apoptosis rates and earlier activation of apoptosis pathways after gamma-irradiation in comparison to beta-irradiation at the same dose rate. Furthermore, irradiation-resistant cells were cross-resistant to CD95 and CD95-resistant cells were cross-resistant to irradiation, indicating that CD95 and irradiation used, at least in part, identical effector pathways. These findings demonstrate that beta-irradiation induces apoptosis and activates apoptosis pathways in leukaemia cells using both mitochondrial and death receptor pathways. Understanding the timing, sequence and molecular pathways of beta-irradiation-mediated apoptosis may allow rational adjustment of chemo- and radiotherapeutic strategies.     

表面活性剂泊洛沙姆188临界胶束浓度的模拟计算

建立了一种介观模拟计算表面活性剂临界胶柬浓度（CMC）的方法。以非离子表面活性剂泊洛沙姆188为研究对象，计算了其在298K下的临界胶束浓度（CMC），分析了泊洛沙姆188在水中相行为和有序参数的变化，为表面活性剂增溶作用的研究提供了基础。     

表面活性剂泊洛沙姆188临界胶束浓度的模拟计算

建立了一种介观模拟计算表面活性剂临界胶束浓度(CMC)的方法。以非离子表面活性剂泊洛沙姆188为研究对象,计算了其在298K下的临界胶束浓度(CMC),分析了泊洛沙姆188在水中相行为和有序参数的变化,为表面活性剂增溶作用的研究提供了基础。     

188Re近距离辐射正常食管组织的病理学变化特点

目的　观察188Re食管支架腔内近距离辐射动物食管组织学形态变化 ,探讨其临床价值。方法　选用约克白猪 ,分 2 2 2MBq、4 4 4MBq和对照支架分别置入食管照射。于照射后 1、3周取食管组织标本作DNA含量分析和病理组织学观察。结果　 2 2 2MBq支架动物 7d食管标本DNA分析亚二倍体含量为 4 .2 3% ,2 1d为 3.6 1%。4 4 4MBq、7d食管组织亚二倍体含量为 9.74 % ,2 1d为 6 .5 4 % ,与对照组 (2 .4 6 %、2 .2 3% )差异显著 (P <0 .0 1)。病理组织形态观察 ,2 2 2MBq、7d食管黏膜炎性改变点状坏死 ,2 1d炎症变化较轻 ,见组织修复、少量纤维增生。4 4 4MBq、7d食管黏膜严重炎症 ,广泛灶状坏死 ,并且有肌肉层损伤 ,2 1d仍可见黏膜片状坏死性损伤及组织修复性纤维化增生。结论　188Reβ源放射性食管支架对食管表浅组织具有明显的电离辐射效应。单次辐射 (吸收 )剂量小于 4 4 4MBq可减轻食管肌层组织的放射反应