BACKGROUND & AIMS: :To improve the circulation time and transfection efficiency of the polyplexes used in gene delivery, a series of Pluronic®/Pluronic®F127-PEI-SS/pDNA complexes (PFPS/pDNA), based on the addition of different kinds of Pluronics® to the reducible disulfide-bonds-containing Pluronic®F127-PEI-SS/pDNA (FPS/pDNA) polyplexes, was prepared and evaluated in Bcap and Hela cells in vitro and in vivo. The addition of Pluronics® with molecular weights and hydrophilic-lipophilic balance (HLBs) different from that in the FPS/pDNA complex resulted in five PFPS(1-5)/pDNA complexes, and the correlation between the structure of the free Pluronic® and the properties of the PFPS/pDNA complexes was investigated. The addition of Pluronics® resulted in slightly larger or same-sized nanoparticles of PFPS/pDNA at a constant N/P ratio. The PFPS copolymer displayed strong stability against DNase I digestion and serum degradation. PFPS-4 containing added Pluronic® L35, with an intermediate HLB of 19, showed a much higher transfection efficiency and less cytotoxicity than FPS or PEI-25 kDa in vitro. PFPS-4 also exhibited a considerably longer blood circulation time than FPS or PEI-25 kDa in vivo in mice, indicating that the addition of an intermediate Pluronic® can enhance the transfection efficiency of gene delivery systems.

背景与目标： : 为了改善用于基因传递的多聚体的循环时间和转染效率，一系列Pluronic®/普朗尼克®基于添加不同种类的F127-PEI-SS/pDNA复合物 (PFPS/pDNA)®到可还原的含二硫键的Pluronic®制备F127-PEI-SS/pDNA (FPS/pDNA) 多复合物，并在体外和体内在Bcap和Hela细胞中进行评价。Pluronics的添加®分子量和亲水亲脂平衡 (HLBs) 与FPS/pDNA复合物中的分子量不同，产生了五个pfp (1-5)/pDNA复合物，以及游离Pluronic的结构之间的相关性®并研究了PFPS/pDNA复合物的性质。Pluronics的添加®以恒定的N/P比产生稍大或相同尺寸的PFPS/pDNA纳米颗粒。PFPS共聚物对DNase I消化和血清降解表现出很强的稳定性。含有添加的Pluronic的PFPS-4®具有19的中间体HLB的L35在体外显示出比FPS或PEI-25 kDa高得多的转染效率和更少的细胞毒性。PFPS-4在小鼠体内的血液循环时间也比FPS或PEI-25 kDa长得多，表明添加了中间的Pluronic®可以提高基因传递系统的转染效率。

BACKGROUND & AIMS: :The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics(®)) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy.

背景与目标： : 特异性酪氨酸激酶抑制剂 (TKIs) 的发展彻底改变了慢性粒细胞白血病 (CML) 的治疗方法。然而，已经描述了肿瘤细胞对TKIs的化学耐药性，并且几种机制解释了多药耐药性 (MDR) 表型，包括P-糖蛋白 (P-gp) 的过表达。这降低了治愈率和肿瘤完全缓解。已经研究了纳米技术工具，以使该领域取得进步。泊洛沙姆 (Pluronics (®)) 已被提议作为药物载体，以提高治疗功效并减少副作用，即使在癌症治疗中也是如此，因为它们具有抑制P-gp的能力。抗精神病药吩噻嗪已被描述为体外针对几种类型肿瘤细胞的有效细胞毒性药物。在这里，我们显示包含吩噻嗪衍生物氯丙嗪 (CPZ) 的纳米结构胶束系统增强了游离CPZ的细胞毒性，并增加了对CML肿瘤细胞的选择性，证明了这些基于泊洛沙姆的包含CPZ的纳米结构系统在癌症治疗中的药理潜力。

BACKGROUND & AIMS: :Polymeric carriers are extensively used in photodynamic therapy (PDT) for increase of efficacy of photosensitizers. Here, we report the influence of nine Pluronic copolymers on phototoxicity of chlorin e6 (Ce6), in particular 5- to 7-fold rise in the phototoxicity caused by hydrophilic Pluronics F127, F108, F68 and F87 and practically no influence on Ce6 of more hydrophobic polymers. The revealed value of 0.2 mg mL(-1) of Pluronic F127 concentration sufficient for half-of-maximal increase of Ce6 photodynamic activity proved to be close to 0.16 mg mL(-1) inherent in well-documented carrier poly(N-vinylpyrrolidone) (PVP). The dissociation constants of Ce6 complexes with Pluronic F127 and PVP that were estimated from UV spectra were 0.252 and 0.036 mg mL(-1) , respectively, indicating higher stability of Ce6 complex with PVP. According to the results of (1) H-NMR studies of Ce6 complexes, the porphyrin interacts not only with hydrophobic regions but also with hydrophilic sides of both polymers.

背景与目标： : 聚合物载体广泛用于光动力疗法 (PDT) 中，以提高光敏剂的功效。在这里，我们报告了9种Pluronic共聚物对氯蛋白e6 (Ce6) 的光毒性的影响，特别是由亲水性Pluronics F127，F108，F68和F87引起的光毒性增加了5至7倍，实际上对Ce6的影响更多疏水性聚合物。0.2 mg mL(-1) 的Pluronic F127浓度的揭示值足以使Ce6光动力活性的最大增加达到0.16 mg mL(-1)，这被证明是在充分证明的载体聚 (N-乙烯基吡咯烷酮) 中固有的 (PVP)。从紫外光谱估计的Ce6与Pluronic F127和PVP配合物的解离常数分别为0.252和0.036 mg mL(-1)，表明Ce6与PVP配合物的稳定性更高。根据 (1) 对Ce6配合物的h-nmr研究结果，卟啉不仅与疏水区域相互作用，而且与两种聚合物的亲水侧相互作用。

BACKGROUND & AIMS: :The membranotropic properties of block co-polymers and their protein conjugates were studied by their effect on the rate of oxygen consumption by isolated liver mitochondria and on thymus-derived lymphocytes. The block co-polymers consisted of poly(ethylene oxide) (PoE) [poly(ethylene glycol)] and poly(propylene oxide) (PoP) to give either PoE-PoP or PoE-PoP-PoE. Both types inhibited uncoupled respiration of liver mitochondria in a medium containing glutamate and malate and also of lymphocytes. They also uncoupled respiration in the presence of succinate in K(+)-containing medium and of lymphocytes. A method is described for linking protein to the block polymers to form conjugates. Such conjugates were formed from alpha-chymotrypsin, BSA and cytochrome c, all of which produced similar effects on the respiration of the isolated mitochondria and lymphocytes. The data suggest that both the block co-polymers and their protein conjugates inhibit the NADH dehydrogenase complex and induce a K(+)-conductivity of the mitochondrial inner membrane; the surface activity of the conjugates allows them to pass through the plasma membrane and interact with the mitochondrial inner membrane.

背景与目标： : 通过对分离的肝线粒体和胸腺来源的淋巴细胞耗氧率的影响，研究了嵌段共聚物及其蛋白质缀合物的膜致特性。嵌段共聚物由聚 (环氧乙烷) (PoE) [聚 (乙二醇)] 和聚 (环氧丙烷) (PoP) 组成，从而得到PoE-PoP或PoE-PoP-PoE。两种类型均抑制含有谷氨酸和苹果酸以及淋巴细胞的培养基中肝线粒体的未偶联呼吸。在含K () 的培养基和淋巴细胞中存在琥珀酸盐的情况下，它们还会解耦呼吸。描述了一种用于将蛋白质连接到嵌段聚合物以形成缀合物的方法。这种结合物是由 α-胰凝乳蛋白酶，BSA和细胞色素c形成的，所有这些结合物对分离的线粒体和淋巴细胞的呼吸产生相似的作用。数据表明，嵌段共聚物及其蛋白质缀合物均抑制NADH脱氢酶复合物并诱导线粒体内膜的K () 电导率; 缀合物的表面活性使它们能够穿过质膜并与线粒体内膜相互作用。

BACKGROUND & AIMS: :We investigated the effect of fatty acid chain length on the binding capacity of drug and fatty acid to Pluronic F127-based microemulsions. This was accomplished by using turbidity experiments. Pluronic-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated Amitriptyline, an antidepressant drug. Sodium salts of C(8), C(10), or C(12) fatty acid were used in preparation of the microemulsion and the corresponding binding capacities were observed. It has been previously determined that, for microemulsions prepared with sodium caprylate (C(8) fatty acid soap), a maximum of 11 fatty acid molecules bind to the microemulsion per 1 molecule of Pluronic F127 and a maximum of 12 molecules of Amitriptyline bind per molecule of F127. We have found that with increasing the chain length of the fatty acid salt component of the microemulsion, the binding capacity of both the fatty acid and the Amitriptyline to the microemulsion decreases. For sodium salts of C(8), C(10) and C(12) fatty acids, respectively, a maximum of approximately 11, 8.4 and 8.3 molecules of fatty acid molecules bind to 1 Pluronic F127 molecule. We propose that this is due to the decreasing number of free monomers with increasing chain length. As chain length increases, the critical micelle concentration (cmc) decreases, thus leading to fewer monomers. Pluronics are symmetric tri-block copolymers consisting of propylene oxide (PO) and ethylene oxide (EO). The polypropylene oxide block, PPO is sandwiched between two polyethylene oxide (PEO) blocks. The PEO blocks are hydrophilic while PPO is hydrophobic portion in the Pluronic molecule. Due to this structure, we propose that the fatty acid molecules that are in monomeric form most effectively diffuse between the PEO "tails" and bind to the hydrophobic PPO groups.

背景与目标： : 我们研究了脂肪酸链长度对药物和脂肪酸与Pluronic F127-based微乳液结合能力的影响。这是通过使用浊度实验完成的。合成了各种组成的基于Pluronic的水包油微乳液，并用浓缩的阿米替林 (一种抗抑郁药) 滴定至浊度。在微乳液的制备中使用C(8)，C(10) 或C(12) 脂肪酸的钠盐，并观察到相应的结合能力。先前已经确定，对于用辛酸钠 (C(8) 脂肪酸皂) 制备的微乳液，每1分子Pluronic F127最多有11个脂肪酸分子与微乳液结合，每分子F127最多有12个阿米替林结合。我们发现，随着微乳中脂肪酸盐成分的链长增加，脂肪酸和阿米替林与微乳的结合能力均降低。对于C(8) 、C(10) 和C(12) 脂肪酸的钠盐，最多约11、8.4和8.3分子的脂肪酸分子与1个Pluronic F127分子结合。我们认为这是由于随着链长的增加，自由单体的数量减少所致。随着链长的增加，临界胶束浓度 (cmc) 降低，从而导致单体减少。Pluronics是由环氧丙烷 (PO) 和环氧乙烷 (EO) 组成的对称三嵌段共聚物。聚丙烯氧化物块PPO夹在两个聚环氧乙烷 (PEO) 块之间。PEO嵌段是亲水的，而PPO是Pluronic分子中的疏水部分。由于这种结构，我们建议单体形式的脂肪酸分子最有效地在PEO “尾巴” 之间扩散并与疏水性PPO基团结合。

BACKGROUND & AIMS: :This study is to prepare and evaluate Pluronics-modified mixed micelle (MM) to deliver polyphenolic myricetin (MYR) across the blood-brain barrier. MYR has been proven to be an effective anticancer agent against glioblastoma cells in our previous studies. However, the poor solubility of MYR limits its access to the brain. In this study, the feasibility of preparing lipid-based MM that combined sodium dodecyl sulphate (SDS) with Pluronic F68 (F68) and Labrasol was investigated. Furthermore, the nonionic surfactant coating technology for the protection of MYR against oxidation, and its attainment in oral bioavailability, was examined. On account of the altered biomaterial properties of F68/SDS-modified lipid-based micelles, myricetin-loaded mixed micelles (MYR-MMs) were prepared by solvent-evaporation method to self-assembly into MMs. The average size of MYR-MMs was 96.3 nm, with negatively charged potential and spherical in shape. The drug loading of MYR-MMs was high with the increased grafting ratio, the more prolonged drug release profile, and more effective killing glioblastoma cells in vitro. Moreover, MYR-MMs showed a higher preference for the brain than free MYR alone, suggesting the novel MMs loaded with MYR could promote absorption and increase relative bioavailability. Taken together, the F68/SDS-modified and Labrasol-modified lipid-based micelles may provide a promising method to deliver polyphenolic compounds across the brain to treat brain tumor.

背景与目标： : 这项研究旨在制备和评估Pluronics修饰的混合胶束 (MM)，以通过血脑屏障传递多酚杨梅素 (MYR)。在我们先前的研究中，MYR已被证明是一种有效的抗胶质母细胞瘤细胞的抗癌剂。然而，MYR的溶解度差限制了它进入大脑。在这项研究中，研究了将十二烷基硫酸钠 (SDS) 与Pluronic F68 (F68) 和Labrasol结合制备基于脂质的MM的可行性。此外，还研究了用于保护MYR免受氧化的非离子表面活性剂涂层技术及其在口服生物利用度中的实现。由于F68/SDS修饰的脂质基胶束的生物材料性质发生了变化，通过溶剂蒸发法制备了载有杨梅素的混合胶束 (myr-mms)，以自组装成MMs。Myr-mms的平均尺寸为96.3 nm，具有带负电的电势和球形。Myr-mms的载药量很高，接枝率增加，药物释放曲线延长，体外杀死胶质母细胞瘤细胞更有效。此外，myr-mms比单独的游离MYR表现出更高的大脑偏好，这表明装有MYR的新型MMs可以促进吸收并增加相对生物利用度。综合而言，F68/SDS修饰和Labrasol修饰的基于脂质的胶束可能提供一种有前途的方法，可将多酚类化合物传递到整个大脑以治疗脑肿瘤。

BACKGROUND & AIMS: PURPOSE:Pluronics are known as inhibitors of multidrug resistance thus making tumor cells sensitive to therapeutic doses of drugs. The purpose of our study consists in revealing molecular targets of the hydrophobic poly(propylene oxide) block of pluronics in living cells and the dependence of the polymers chemosensitizing efficiency upon targeting. METHODS:A photo sensitive tracer was attached to the hydrophobic poly(propylene oxide) block of 3H-labeled tert-Bu-EO-PO copolymer. The conjugate was used for treatment cells in culture. We searched for its complexes with cellular lipids or proteins using RP TLC and SDS-electrophoresis, respectively. The chemosensitizing efficiency of pluronics was evaluated by their least concentrations sufficient for MDR reversion (CMDR). RESULTS:The poly(propylene oxide) block inserts in the lipid core of plasma membrane. No preferential binding of the conjugate with any cellular protein, particularly P-gp, has been detected. FITC-labeled pluronic L61 bound to alcohol insoluble cellular targets did not participate in MDR reversion. CMDR values of 13 block copolymers have been determined. These values inversely correlated with the polymers affinity toward lipids and the ability to accelerate flip-flop. CONCLUSION:Insertion of the hydrophobic poly(propylene oxide) block of amphiphiles in the lipid core of plasma membrane and acceleration of flip-flop of lipids underlie the mechanism of MDR reversion.

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BACKGROUND & AIMS: BACKGROUND/AIM:Fragment reattachment is a conservative and a valid alternative to a direct composite restoration. The aim of this study was to evaluate the effect of commonly available storage media on the fracture resistance of reattached fragments. MATERIAL AND METHODS:Sixty sound human maxillary incisors were divided into three groups, the teeth were then sectioned and the fragments were kept dry (Group A), stored in milk (Group B) and in saline (Group C) for 24 h. The fragments were then reattached using simple reattachment technique with flowable composite resin. These teeth were then subjected to thermocycling and the fracture resistance of these reattached fragments were recorded. The mode of fracture was also recorded. RESULTS:Group C (saline) recorded the highest mean fracture resistance (76.9 N) followed by Group B (milk) and Group C (dry), (38.7 N and 27.2 N, respectively). Most of the samples in Group A (65%) and Group C (70%) showed adhesive fracture, whereas 50% of the samples in Group B showed adhesive fracture. CONCLUSIONS:Fragments stored in saline and milk showed greater fracture resistance than those kept dried.

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BACKGROUND & AIMS: :In order to improve surface hydrophilicity, blood compatibility and cell-antiadhesion of polypropylene (PP) film, polypropylene oxide (PPO)-polyethylene oxide-PPO used as macromolecular surface modifier through physical blending. Surface properties of blended PP/Pluronic F127 (PF127) samples were investigated by attenuated total reflection infrared spectroscopy and water contact angle measurements. Results demonstrated that PF127 migrated to the surface. Thus, mechanical properties of blended PP/PF127 samples with the aim of the revealing the effects of the presence of modifier in the bulk were investigated through differential scanning calorimetry, X-ray diffraction, and tensile tests. The biocompatibility and hemocompatibility of modified PP films were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, platelet-rich plasma, and hemolysis tests. These results showed excellent anticell and antiplatelet adhesion which deems the prepared blended films proper biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 652-662, 2018.

背景与目标： : 为了提高聚丙烯 (PP) 膜的表面亲水性，血液相容性和细胞抗粘附性，通过物理共混将聚丙烯氧化物 (PPO)-聚环氧乙烷-PPO用作大分子表面改性剂。通过衰减全反射红外光谱和水接触角测量研究了共混PP/Pluronic F127 (PF127) 样品的表面性能。结果表明PF127迁移到地表。因此，通过差示扫描量热法，x射线衍射和拉伸试验研究了共混PP/PF127样品的机械性能，目的是揭示本体中改性剂存在的影响。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴铵 (MTT) 测定，富血小板血浆和溶血试验评估了改性PP薄膜的生物相容性和血液相容性。这些结果显示出优异的抗细胞和抗血小板粘附性，认为制备的共混膜是合适的生物材料。©2017威利期刊公司J生物材料Res部分A: 106A: 652-662，2018。

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