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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BACKGROUND & AIMS: :An amphiphilic copolymer, Pluronic F127, has been deposited, by adsorption, to the skin of human volunteers and the ability of the coated skin to resist bacterial colonisation has been evaluated. In parallel, the ability of the same copolymer to act as a bacterial release agent has been evaluated. In both cases, F127 proved to be of little added value in formulations designed to suppress the bacterial colonisation of human skin.

背景与目标： : 两亲性共聚物Pluronic F127已通过吸附沉积到人类志愿者的皮肤上，并评估了涂层皮肤抵抗细菌定植的能力。同时，已经评估了相同共聚物充当细菌释放剂的能力。在这两种情况下，F127在旨在抑制人类皮肤细菌定植的配方中几乎没有附加值。

BACKGROUND & AIMS: :Mosapride belongs to class IV in Biopharmaceutics Classification System and is used in the treatment of reflux esophagitis. It exhibits poor bioavailability due to limited permeability, solubility and extensive first-pass metabolism. In this study, intranasal mosapride-loaded cross-linked xyloglucan Pluronic micelles (MOS-XPMs) was formulated and optimized to improve the low solubility & bioavailability of MOS. The solid dispersion technique using 23 full factorial design was applied. (MOS-XPMs) (F4) had the highest desirability value (0.952) and, therefore, it was selected as an optimal system. Xyloglucan cross-linked in the shell of Pluronic micelles offered improved stability and mucoadhesiveness to MOS-XPMs. 1H NMR spectra ensured the cross-linking of xyloglucan with Pluronic micelle shell and micelle stabilization. A Pharmacodynamic study revealed that MOS-XPMs showed 1.5-fold increase in duodenal and cecal motility compared to MOS suspension and 1.7-fold increase compared to the oral marketed product. The new MOS-XPMs were shown to be successful at improving the therapeutic efficacy of mosapride.

背景与目标： : 莫沙必利在生物制药分类系统中属于IV类，用于治疗反流性食管炎。由于渗透性，溶解性和广泛的首过代谢，它表现出较差的生物利用度。在这项研究中，配制并优化了鼻内mosapride负载的交联木葡聚糖多元胶束 (mos-xpms)，以改善MOS的低溶解度和生物利用度。采用23个全因子设计的固体分散技术。(Mos-xpms) (F4) 具有最高的期望值 (0.952)，因此，它被选为最佳系统。在多元胶束壳中交联的木葡聚糖提供了改善的稳定性和对mos-xpms的粘膜粘附性。1H NMR光谱确保了木葡聚糖与多元胶束壳的交联和胶束稳定。药效学研究表明，与MOS悬浮液相比，mos-xpms显示十二指肠和盲肠运动增加1.5倍，与口服销售产品相比增加1.7倍。新的mos-xpm被证明在改善莫沙必利的治疗效果方面是成功的。

BACKGROUND & AIMS: :Novel biomaterials have been prepared in which glycosaminoglycans (GAGs) are chemically modified to create amphiphilic multiblock copolymers that are able to adhere to hydrophobic surfaces and can self-assemble into cross-linker-free hydrogels. First, the triblock poly(ethylene oxide)-polypropylene oxide copolymers (Pluronics) were converted into the previously unknown aminooxy (AO) derivatives. Both mono-AO and bis-AO Pluronics (AOPs) were synthesized and fully characterized in order to prepare tetrablock and pentablock copolymers, respectively. Second, the AOPs were coupled to the uronic acid carboxylates of heparin (HP) and hyaluronic acid (HA) using carbodiimide chemistry in order to give the previously undescribed amidooxy GAG derivatives. The coupling chemistry was confirmed using a newly prepared fluorescent AO reagent. Third, AOP-heparin and AOP-fluorescently labeled heparin were shown to adsorb efficiently to polystyrene surfaces, as determined by IL-8 based ELISA and fluorescence measurements, respectively. Fourth, AOP-linked fluorescently labeled HA was shown to adsorb efficiently to plastic surfaces. Finally, three different AOPs were evaluated for self-assembling hydrogel formation by AOP-HA pentablock polymers. In short, AOP-GAG adducts are semisynthetic amphiphilic biomacromolecules that offer a range of valuable practical opportunities for surface modification, preparation of cross-linker-free hydrogels, and formation of self-assembling mimics of the extracellular matrix.

背景与目标： : 已经制备了新型生物材料，其中糖胺聚糖 (gag) 经过化学修饰以产生两亲性多嵌段共聚物，这些共聚物能够粘附在疏水表面上并可以自组装成无交联剂的水凝胶。首先，将三嵌段聚 (环氧乙烷)-聚丙烯氧化物共聚物 (Pluronics) 转化为先前未知的氨基氧基 (AO) 衍生物。合成了mono-AO和bis-AO Pluronics (AOPs)，并对其进行了充分表征，分别制备了四嵌段和五嵌段共聚物。其次，使用碳二亚胺化学将aop与肝素 (HP) 和透明质酸 (HA) 的糖醛酸羧酸盐偶联，以产生先前未描述的酰胺氧GAG衍生物。使用新制备的荧光AO试剂确认了偶联化学。第三，AOP-肝素和AOP-荧光标记的肝素被显示为分别通过基于IL-8的ELISA和荧光测量来有效地吸附到聚苯乙烯表面。第四，AOP连接的荧光标记的HA被证明可以有效地吸附到塑料表面上。最后，评估了三种不同的AOP通过AOP-HA五嵌段聚合物形成的自组装水凝胶。简而言之，AOP-GAG加合物是半合成的两亲性生物大分子，为表面改性，无交联剂水凝胶的制备以及细胞外基质的自组装模拟物的形成提供了一系列有价值的实践机会。

BACKGROUND & AIMS: PURPOSE:This investigation was performed to study the effects of Pluronic block copolymers and Cremophor EL on intestinal lipoprotein processing and to investigate a potential link between lipoprotein processing and P-glycoprotein. METHODS:Caco-2 cells were used to monitor changes in lipoprotein production and secretion following exposure to excipients. Effects on P-glycoprotein were monitored using cyclosporin A as a model substrate. RESULTS:A range of surfactants commonly used as pharmaceutical excipients in lipid-based oral drug delivery systems, including Pluronics block copolymers L81, P85, and F68 and Cremophor EL, inhibited intestinal lipoprotein secretion. The effects were concentration dependent and reversible. The mechanism of inhibition appears to be related to the assembly and secretion of lipoproteins rather than to initial intracellular triglyceride synthesis. A strong correlation was found between excipient-mediated inhibition of lipoprotein secretion and inhibition of P-glycoprotein efflux, implying a link between the two biochemical processes. CONCLUSION:The ability of such bioactive excipients to simultaneously manipulate different cellular processes must be considered in selecting excipients for oral drug delivery systems. Such information is particularly relevant when the drug is lipophilic, a candidate for P-glycoprotein efflux, and where intestinal lymphatic targeting via chylomicron stimulation is desirable.

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BACKGROUND & AIMS: :Pluronics are triblock copolymers, in which two hydrophilic poly (ethylene oxide) (PEO) blocks are connected via a hydrophobic poly propylene oxide (PPO) block. Because of their low molecular weight and high content of PEO, Pluronics have demonstrated the micellization phenomenon, which is dependent on temperature and/or concentration. With an understanding of micellization phenomenon in more detail, information on the morphology, micelle core radius, aggregation behavior with critical micelle concentration (CMC) and critical micelle temperature (CMT) and so on has been revealed. Based on this acquired information, various studies have been performed for biomedical applications such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. This review discusses the delivery of small molecules and macromolecules using Pluronic-based NPs and their composites.

背景与目标： : Pluronics是三嵌段共聚物，其中两个亲水性聚 (环氧乙烷) (PEO) 嵌段通过疏水性聚环氧丙烷 (PPO) 嵌段连接。由于其低分子量和高含量的PEO，Pluronics表现出胶束化现象，这取决于温度和/或浓度。通过对胶束化现象的更详细的了解，揭示了胶束的形态，胶束核心半径，临界胶束浓度 (CMC) 和临界胶束温度 (CMT) 的聚集行为等信息。基于这些获得的信息，已经针对生物医学应用进行了各种研究，例如药物递送系统，组织再生支架和生物表面活性剂。这篇评论讨论了使用基于Pluronic的NPs及其复合材料的小分子和大分子的传递。

BACKGROUND & AIMS: :We investigated a series of small-sized polyethylenimine (PEI, 0.8/1.2 k)-conjugated pluronic copolymers (PCMs) for their potential to enhance delivery of an antisense phosphorodiamidate morpholino oligomer (PMO) in vitro and in dystrophic mdx mice. PCM polymers containing pluronics of molecular weight (Mw) ranging 2-6 k, with hydrophilic-lipophilic balance (HLB) 7-23, significantly enhanced PMO-induced exon-skipping in a green fluorescent protein (GFP) reporter-based myoblast culture system. Application of optimized formulations of PCMs with PMO targeted to dystrophin exon 23 demonstrated a significant increase in exon-skipping efficiency in dystrophic mdx mice. Consistent with our observations in vitro, optimization of molecular size and the HLB of pluronics are important factors for PCMs to achieve enhanced PMO delivery in vivo. Observed cytotoxicity of the PCMs was lower than Endo-porter and PEI 25 k. Tissue toxicity of PCMs in muscle was not clearly detected with the concentrations used, indicating the potential of the PCMs as effective and safe PMO carriers for treating diseases such as muscular dystrophy.

背景与目标： : 我们研究了一系列小型聚乙烯亚胺 (PEI，0.8/1.2 k) 共轭的多元共聚物 (pcm)，它们在体外和营养不良的mdx小鼠中增强反义二酰磷酰吗啉代低聚物 (PMO) 的递送的潜力。PCM聚合物，其分子量为2-6 k，具有亲水亲脂平衡 (HLB) 7-23，可显着增强基于绿色荧光蛋白 (GFP) 报告基因的成肌细胞培养系统中PMO诱导的外显子跳跃。应用针对肌营养不良蛋白外显子23的PMO优化的pcm制剂证明了营养不良mdx小鼠外显子跳跃效率的显着提高。与我们在体外观察的结果一致，分子大小的优化和pluronics的HLB是pcm在体内实现增强PMO递送的重要因素。观察到的PCMs的细胞毒性低于Endo-porter和PEI 25 k。使用的浓度无法清楚地检测到PCMs在肌肉中的组织毒性，这表明PCMs可能是治疗诸如肌营养不良的疾病的有效和安全的PMO载体。