Poly(2-oxazoline)s (POx) are currently discussed as an upcoming platform for biomaterials design and especially for polymer therapeutics. POx meets several requirements needed for the development of next-generation polymer therapeutics such as biocompatibility, high modulation of solubility, variation of size, architecture as well as chemical functionality. Although in the early 1990s first and promising POx-based systems were presented but the field lay dormant for almost two decades. Only very recently, POx based polymer therapeutics came back into the focus of very intensive research. In this review, we give an overview on the chemistry and physicochemical properties of POx and summarize the research of POx-protein conjugates, POx-drug conjugates, POx-based polyplexes and POx micelles for drug delivery.

According to Fukumoto's method, a new series of ionic liquids (ILs) based on alanine, [Cnmim][Ala] ( n=2,3,4,5,6), which comprise 1-alkyl-3-methylimidazolium cation ([Cnmim](+)) and alanine anions ([Ala] (-)), were prepared and characterized. In terms of standard addition method, the density and surface tension of amino acid ILs [Cnmim][Ala] (1-alkyl-3-methylimidazolium alpha-aminopropionic acid salt) were measured in the temperature range 293.15-343.15+/-0.05 K. The volume and surface properties of the ILs [Cnmim][Ala] were discussed. A new method of determining parachor of ionic compound was proposed and was applied to estimate the physicochemical properties of amino acid ionic liquids (AAILs): molecular volume, surface tension, molar enthalpy of vaporization, and thermal expansion coefficient. In comparison with Deetlefs's method of using neutral parachor contribution, the method proposed in this work makes smaller error in estimating properties of AAILs.

Overexpression of the receptor tyrosine kinase p185ErbB2 confers Taxol resistance in breast cancers. Here, we investigated the underlying mechanisms and found that overexpression of p185ErbB2 inhibits Taxol-induced apoptosis. Taxol activates p34Cdc2 kinase in MDA-MB-435 breast cancer cells, leading to cell cycle arrest at the G2/M phase and, subsequently, apoptosis. A chemical inhibitor of p34Cdc2 and a dominant-negative mutant of p34Cdc2 blocked Taxol-induced apoptosis in these cells. Overexpression of p185ErbB2 in MDA-MB-435 cells by transfection transcriptionally upregulates p21Cip1, which associates with p34Cdc2, inhibits Taxol-mediated p34Cdc2 activation, delays cell entrance to G2/M phase, and thereby inhibits Taxol-induced apoptosis. In p21Cip1 antisense-transfected MDA-MB-435 cells or in p21-/- MEF cells, p185ErbB2 was unable to inhibit Taxol-induced apoptosis. Therefore, p21Cip1 participates in the regulation of a G2/M checkpoint that contributes to resistance to Taxol-induced apoptosis in p185ErbB2-overexpressing breast cancer cells.

BackgroundNuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro.Methods and ResultsIn vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro.ConclusionsThese results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

Many current nanoformulations of taxanes are hampered by low drug-loading capacity and unfavorable physicochemical characteristics such as large particles size (>100 nm) and/or low size uniformity. We have previously reported on taxane nanoformulations, based on poly(2-oxazoline) polymeric micelles that display an extremely high taxane loading capacity (>40% w/w) and particle size below 50 nm. Previous work was based on a triblock copolymer having poly(2-butyl-2oxazoline) as the hydrophobic block and poly(2-methyl-2-oxazoline) as the hydrophilic blocks. This paper explores the effects of various formulation parameters such as (i) the drug and polymer structure; (ii) the drug and polymer concentration; and (iii) the composition of aqueous medium on the solubilization behavior and physicochemical properties of the resulting formulations. In addition, in vitro anticancer activity is reported. Despite numerous variations of the hydrophobicity, polarity or addition of aromatic residues in the hydrophobic core, the triblock copolymer with the poly(2-butyl-2-oxazoline) block remains the polymer with the highest drug-loading capacity. Notably, the formulation was easily scalable with uncompromised encapsulation efficacy, loading capacity, and physicochemical properties. The taxane formulations were stable upon storage (water, saline, and dextrose solution) for 1-2 weeks and could be lyophilized and re-dispersed without compromising the formulation properties. Furthermore, the micelles remained stable upon dilution. The drug-loaded poly(2-oxazoline) micelles showed high toxicity against several cancer cell lines. Taken together, these results underscore the potential of poly(2-oxazoline) micelles as formulation excipient for taxanes and possibly other hydrophobic drugs. Figure 10. Stability of 50 g/l T1 micelle formulations of (a) paclitaxel (39.7 g/l) and (b) docetaxel (40.6 g/l) in DI water, 5% dextrose solution (DEX) or phosphate buffered saline at room temperature. This figure is available in colour online at wileyonlinelibrary.com/journal/pat Y. SEO ET AL.wileyonlinelibrary.com/journal/pat