泊洛沙姆407水溶液的流变学性质

本文对泊洛沙姆407(商品名为普朗尼克F127)进行了流变学性质的考察。通过剪切速率触变性实验、温度敏感性实验和多次升温后表观黏度复原性实验得到了泊洛沙姆407各项流变学参数。结果表明,随着泊洛沙姆407水溶液浓度的提高,其由牛顿流体转变为假塑性流体,触变性和胶凝温度均逐渐降低(15.25%泊洛沙姆407可在体温下形成凝胶)。本文为泊洛沙姆407作为凝胶剂基质的应用提供了可参考的流变学数据。     

泊洛沙姆407的基础和药剂学新进展

目的介绍泊洛沙姆407的基础和药剂学新进展.方法通过查阅近年来国内外的相关文献,选取有代表性的学术期刊进行综述.结果泊洛沙姆407安全性好,在缓、控释凝胶系统及栓剂等剂型中有广泛的应用.结论泊洛沙姆407是安全、理想的药用辅料.     

聚乙烯亚胺的修饰及其作为基因载体的研究

目的:考察聚氧乙烯硬脂酸酯(POES)修饰聚乙烯亚胺(PEI)后聚合物的细胞毒性及其与DNA形成复合物后的载体性质。方法:使用琥珀酰亚胺碳酸脂法将POES连接在PEI上,通过1H-NMR确定接枝聚合物的结构,将接枝聚合物与DNA形成复合物后考察其琼脂糖凝胶电泳行为及测定其粒径、Zeta电位;MTT法考察接枝聚合物的细胞毒性,使用质粒pGL3-lus作为报告基因,测定虫荧光素酶活性以评价复合物对Hela细胞的转染效率。结果:1H-NMR结果表明接枝聚合物具有较高的纯度。凝胶电泳表明接枝聚合物对DNA的包裹能力随着N/P值的增加而升高,随着POES接枝数目的增大而降低。复合物的粒径小于300nm,Zeta电位随N/P值的增加而升高。接枝聚合物细胞毒性显著低于PEI,POES接枝数目低的聚合物转染效率较高。结论:POES修饰的PEI可以作为一种有效的非病毒基因载体。     

聚乙烯亚胺非病毒基因载体结构修饰研究进展

聚乙烯亚胺（PEI）作为最经典的非病毒基因载体之一,由于其高转染效率,在基因递送领域受到极大的关注,但其毒性限制了聚乙烯亚胺的应用。本文综述了对聚乙烯亚胺进行不同的结构修饰,如多糖修饰、PEG修饰和低分子聚乙烯亚胺衍生物等,以实现在不显著降低转染效率的前提下减少细胞毒性。     

不同因素对去甲斑蝥素—泊洛沙姆407缓释制剂体外释放度的影响

目的：了解溶出介质温度、转盘速度及泊洛沙姆407浓度对去甲斑蝥素／泊洛沙姆407缓释制剂释放动力学的影响。方法：采用紫外分光光度法,对去甲斑蝥素在不同情况下的体外释放度进行考察。结果：去甲斑蝥素随泊洛沙姆407凝胶的溶解而逐步释放,随着介质温度升高、转盘速度加快及辅料浓度的降低,去甲斑蝥素释放度相应增加。结论：去甲斑蝥素从泊洛沙姆407中的释放速度与介质温度、转蓝速度呈线性正相关,而与泊洛沙姆407的浓度呈线性负相关。     

聚乙烯亚胺介导基因转染的影响因素研究

目的研究非病毒基因载体聚乙烯亚胺（PEI）介导基因转染的影响因素。方法采用透射电镜观察PEI与DNA形成复合物的形态,分别考察质粒量、复合物形成时间、复合物在细胞上作用时间和氮磷比（N/P）对转染效率的影响,以筛选较优的转染条件。结果PEI可有效地与DNA形成复合物,当质粒量为每孔2μg、复合物形成时间为30min、复合物在细胞上的作用时间为4h且N/P为20时转染效率最高。结论PEI可作为合成新型非病毒载体的骨架,但必须控制有关因素才能得到最佳的和可重复的转染结果。     

泊洛沙姆407在制剂中的应用进展

泊洛沙姆407是医药领域应用非常广泛的一种辅料.本文主要介绍了泊洛沙姆407的理化性质,总结了其在眼部给药、经皮给药、直肠给药、阴道给药、注射给药中的应用情况、存在的问题和发展前景.     

丙烯酸-泊洛沙姆407共聚物的合成及其原位胶凝性质

目的制备丙烯酸和泊洛沙姆407构成的共聚物,研究其温度敏感的原位胶凝性质。方法将泊洛沙姆407溶于丙烯酸单体,引发聚合反应,产物用红外光谱和凝胶渗透色谱表征。用旋转黏度计测定共聚物水溶液的黏度随温度的变化。以维生素B12为模型药物,研究药物的释放性质。结果较低浓度的丙烯酸泊洛沙姆407共聚物水溶液具有受热原位胶凝的性质,其胶凝特征与共聚物的组成、浓度、溶液pH等有关,共聚物凝胶可延缓药物释放。结论丙烯酸泊洛沙姆407共聚物可望应用于黏膜给药的原位凝胶递药系统。     

Modification of the Copolymers Poloxamer 407 and Poloxamine 908 can Affect the Physical and Biological Properties of Surface Modified Nanospheres

Purpose. To investigate the effects of the modification of the copolymers poloxamer 407 and poloxamine 908 on the physical and biological properties surface modified polystyrene nanospheres. Methods. A method to modify poloxamer 407 and poloxamine 908, introducing a terminal amine group to each PEO chain has been developed. The aminated copolymers can be subsequently radiolabelled with lodinated (I¹²⁵) Bolton-Hunter reagent. The aminated copolymers were used to surface modify polystyrene nanospheres. The physical and biological properties of the coated nanospheres were studied using particle size, zeta potential, in vitro non-parenchymal cell uptake and in vivo biodistribution experiments. Results. The presence of protonated amine groups in the modified copolymers significantly affected the physical and biological properties of the resulting nanospheres, although the effects were copolymer specific. The protonated surface amine groups in both copolymers reduced the negative zeta potential of the nanospheres. Acetylation of the copolymer's free amine groups resulted in the production of nanospheres with comparable physical properties to control unmodified copolymer coated nanospheres. In vivo, the protonated amine groups in the copolymers increased the removal of the nanospheres by the liver and spleen, although these effects were more pronounced with the modified poloxamer 407 coated nanospheres. Acetylation of the amine groups improved the blood circulation time of the nanospheres providing modified poloxamine 908 coated nanospheres with comparable biological properties to control poloxamine 908 coated nanospheres. Similarly, modified poloxamer 407 coated nanospheres had only slightly reduced circulation times in comparison to control nanospheres. Conclusions. The experiments have demonstrated the importance of copolymer structure on the biological properties of surface modified nanospheres. Modified copolymers, which possess comparable properties to their unmodified forms, could be used in nanosphere systems where antibody fragments can be attached to the copolymers, thereby producing nanospheres which target to specific body sites.     

Fluorescence spectroscopy studies on micellization of poloxamer 407 solution

It has been reported that at low temperature region, poloxamers existed as a monomer. Upon warming, an equilibrium between unimers and micelles was established, and finally micelle aggregates were formed at higher temperature. In this study, the fluorescence spectroscopy was used to study the micelle formation of the poloxamer 407 in aqueous solution. The excitation and emission spectra of pyrene, a fluorescence probe, were measured as a function of the concentration of poloxamer 407 and temperature. A blue shift in the emission spectrum and a red shift in the excitation spectrum were observed as pyrene transferred from an aqueous to a hydrophobic micellar environment. From the I1/I3 and I339/I333 results, critical micelle concentration (cmc) and critical micelle temperature (cmt) were determined. Also, from the fluorescence spectra of the probe molecules such as 8-anilino-1-naphthalene sulfonic acid and 1-pyrenecarboxaldehyde, the blue shift of the lambdamax was observed. These results suggest a decrease in the polarity of the microenvironment around probe because of micelle formation. The poloxamer 407 above cmc strongly complexed with hydrophobic fluorescent probes and the binding constant of complex increased with increasing the hydrophobicity of the probe.     

Effects on splenic, hepatic, hematological, and growth parameters following high-dose poloxamer 407 administration to rats

The nonionic surfactant poloxamer 407, NF (PIuronic ^® F-127, NF) has previously been shown to produce marked hyperlipidemia in rats at a dose of 1.5 g/kg for greater than 96 h following a single intraperitoneal (i.p.) injection (Wout et al. J. Parenter. Sci. Technol., 46 (1992) 192–200). In an effort to characterize any potential toxicity of the polymeric vehicle to various organ systems in the rat following multiple i.p. injections, a dose of 0.33 g/kg per day (10% w/w solution) or 1.0 g/kg per day (30% w/w solution) of poloxamer 407 was administered once daily for 4 consecutive days. When compared to control (non-injected) animals, rats injected with 0.33 g/kg per day of poloxamer 407 did not show a significant (p > 0.05) increase or decrease in spleen, liver, or total body weight. A complete blood count (CBC) with a white blood cell (WBC) differential was performed on blood samples collected on day five from rats injected with poloxamer 407 at both doses. The CBC with WBC differentia] was conducted to assess any changes in the WBC count, percent lymphocytes (LY), percent monocytes (MO), percent granulocytes (GR), red blood cell (RBC) count, hemoglobin (HGB), percent hematocrit (HCT), and the mean corpuscular volume (MCV) following administration of poloxamer 407. Rats injected i.p. with a dose of 0.33 g/kgper day of poloxamer 407 for 4 days demonstrated a significant (p < 0.05) increase in the number of MO when compared to controls. Administration of 1.0 g/kg per day of poloxamer 407 to rats for 4 days demonstrated distinct splenomegaly when compared to non-injected control animals. In addition, a significant (p < 0.05) reduction in body weight and significant (p < 0.05) decrease in the percent LY, RBCs, HGB, and percent HCT were noted. Lastly, a significant (p < 0.05) increase in the number of WBCs and the percent MO was observed in this same group of rats. However, rats administered 1.0 g/kg per day of poloxamer 407 for 4 days were observed to have no detectable changes in the values of the MCV, the percent GR, or liver-to-body weight ratio when compared to control animals. Thus, repetitive i.p. injections of poloxamer 407 to rats at a dose of 1.0 g/kg per day for four days results in splenomegaly and a reduction in total body weight. Splenomegaly in rats administered poloxamer 407 at a dose of 1.0 g/kg per day resulted from red pulp expansion due to infiltration of macrophages which contained phagocytized lipids.     

Intrapericardial administration of novel DNA formulations based on thermosensitive Poloxamer 407 gel

Inherited cardiopathies are leading to life-threatening conditions such as heart failure. Moreover, treatments currently available fail in altering the cardiac phenotype. Thus, gene therapy appears as an attracting alternative to conventional treatments. However, gene delivery remains a major hurdle in achieving this goal. To obtain regional delivery of plasmid DNA, intrapericardial administration seems to be an interesting approach. In order to improve retention time at the site of injection, formulations based on a thermosensitive gel of Poloxamer 407 were assessed. Protection and condensation of plasmid DNA was initially performed through complexation with polyethyleneimine (PEI), a widely used polymer. Characterization of the size and zeta potential of the complexes suggested interactions between the polyplexes and the Poloxamer gel through significant increase of the size of the polyplexes and shielding of the surface charges. In vivo evaluation has highlighted the toxicity of PEI/DNA polyplexes toward the myocardium. However, feasibility of intrapericardial injection of Poloxamer based formulations as well as their very low toxicity has been established.     

Poloxamer 407 increases soluble adhesion molecules,ICAM‐1, VCAM‐1 and E‐selectin,in C57BL/6 mice

Objectives Soluble shedded forms of cell adhesion molecules (sCAMs) found in plasma are regarded as surrogate markers for the cellular expression of CAMs. The presence of oxidised low‐density lipoprotein (ox‐LDL) cholesterol and fatty acids in the plasma, hypertriglyceridaemia and reduced plasma concentrations of high‐density lipoprotein cholesterol (HDL‐C) are all thought to stimulate an increase in the cellular expression of CAMs such as vascular cell adhesion molecule‐1 (VCAM‐1), intercellular adhesion molecule‐1 (ICAM‐1) and E‐selectin. Our objectives were to determine how plasma levels of the soluble CAMs were modulated in a mouse model of dyslipidaemia induced chemically with poloxamer 407, and how these changes might be related to changes in the plasma concentrations of total cholesterol, HDL‐C, non‐HDL‐C and triglycerides. Methods C57BL/6 mice were given a single intraperitoneal dose of poloxamer 407 (0.5 g/kg) and plasma concentrations of lipid fractions and sCAMs were measured at predetermined time points thereafter. Key findings The plasma concentrations of each sCAM were significantly increased in our mouse model of atherogenic dyslipidaemia compared with control mice administered saline, although the temporal relationship between the plasma sCAM concentration‐time profiles and the plasma lipid concentration‐time profiles were not coincident. Conclusions The atherogenic profile in our mouse model was associated with increases in the plasma concentrations of sICAM‐1, sVCAM‐1 and sE‐selectin. These changes precede the formation of atherosclerotic lesions shown in previous work. This suggests the use of these sCAMs as biomarkers of future atheroma formation in this particular animal model.     

瑞舒伐他汀对poloxamer407诱导的小鼠高血脂模型血脂水平的影响

目的观察瑞舒伐他汀对poloxamer 407(P-407)诱导的小鼠高血脂模型血脂水平的影响。方法小鼠于腹腔注射P-407前先以瑞舒伐他汀(2或10 mg/kg)连续灌胃,并于腹腔注射P-407(0.3 g/kg)后3 h再次灌胃瑞舒伐他汀。以注射P-407前及注射后第3、4、24及48 h血甘油三酯和胆固醇水平评价瑞舒伐他汀的疗效,同时观察造模后24 h高密度脂蛋白-胆固醇水平。结果瑞舒伐他汀组血清甘油三酯和胆固醇水平减低,具有显著的量效关系,且作用可持续至造模后的48 h。瑞舒伐他汀组小鼠造模后24 h血清高密度脂蛋白-胆固醇水平显著升高(P<0.05)。结论瑞舒伐他汀可有效降低P-407诱导的高血脂模型小鼠的血脂水平。     

泊洛沙姆固体分散体对穿心莲内酯溶出特性的影响

目的:考察泊洛沙姆固体分散体对难溶性药物穿心莲内酯体外溶出特性的影响。方法:以泊洛沙姆为载体材料,采用熔融法制备不同比例的穿心莲内酯-泊洛沙姆固体分散体,并考察其体外溶出特性。通过红外光谱和X射线衍射图谱研究药物在固体分散体的存在状态。结果:与穿心莲内酯空白药物相比,穿心莲内酯固体分散体在蒸馏水、pH1.2盐酸溶液与pH6.8磷酸盐缓冲液中溶出速率明显提高,载药固体分散体15min时累积释药量是穿心莲内酯空白药物的3.6倍;穿心莲内酯以微晶态高度分散于载体材料中。结论:以泊洛沙姆188为载体制备穿心莲内酯固体分散体,能有效提高难溶性药物的溶出速率。     

三种转染试剂对人脑胶质瘤细胞U251的作用

目的：研究转染试剂Lipofectin、DOTAP和FuGENE6介导反义c-myc基因转染人脑胶质瘤细胞U251的作用。方法：将可在真核细胞表达人反义c-myc基因的质粒pCED4ASCMH分别与转染试剂Lipofectin、DOTAP和FuGENE6结合,转染到人脑胶瘤细胞U251中,转染的第24,48,72和96小时用MTT比色法检测细胞活性并进行比较。结果：转染实验组较对照组细胞活性均降低30％－40％。结论：三种转染试剂介导反义c-myc基因质粒DNA转染U251细胞具有抑制细胞增殖、降低细胞活性、促进细胞死亡的作用。