Poly(2-oxazoline) hydrogels : state-of-the-art and emerging applications

The synthesis of poly(2-oxazoline)s has been known since the 1960s. In the last two decades, they have risen in popularity thanks to improvements in their synthesis and the realization of their potential in the biomedical field due to their stealth properties, stimuli responsiveness, and tailorable properties. Even though the bulk of the research to date has been on linear forms of the polymer, they are also of interest for creating network structures due to the relatively easy introduction of reactive functional groups during synthesis that can be cross-linked under a variety of conditions. This opinion article briefly reviews the history of poly(2-oxazoline)s and examines the in vivo data on soluble poly(2-oxazoline)s to date in an effort to predict how hydrogels may perform as implantable materials. This is followed by an overview of the most recent hydrogel synthesis methods and emerging applications, and is concluded with a section on the future directions predicted for these fascinating yet underutilized polymers

Judging enzyme-responsive micelles by their covers : direct comparison of dendritic amphiphiles with different hydrophilic blocks

Enzymatically degradable polymeric micelles have great potential as drug delivery systems, allowing the selective release of their active cargo at the site of disease. Furthermore, enzymatic degradation of the polymeric nanocarriers facilitates clearance of the delivery system after it has completed its task. While extensive research is dedicated toward the design and study of the enzymatically degradable hydrophobic block, there is limited understanding on how the hydrophilic shell of the micelle can affect the properties of such enzymatically degradable micelles. In this work, we report a systematic head-to-head comparison of well-defined polymeric micelles with different polymeric shells and two types of enzymatically degradable hydrophobic cores. To carry out this direct comparison, we developed a highly modular approach for preparing clickable, spectrally active enzyme-responsive dendrons with adjustable degree of hydrophobicity. The dendrons were linked with three different widely used hydrophilic polymers-poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and poly(acrylic acid) using the CuAAC click reaction. The high modularity and molecular precision of the synthetic methodology enabled us to easily prepare well-defined amphiphiles that differ either in their hydrophilic block composition or in their hydrophobic dendron. The micelles of the different amphiphiles were thoroughly characterized and their sizes, critical micelle concentrations, drug loading, stability, and cell internalization were compared. We found that the micelle diameter was almost solely dependent on the hydrophobicity of the dendritic hydrophobic block, whereas the enzymatic degradation rate was strongly dependent on the composition of both blocks. Drug encapsulation capacity was very sensitive to the type of the hydrophilic block, indicating that, in addition to the hydrophobic core, the micellar shell also has a significant role in drug encapsulation. Incubation of the spectrally active micelles in the presence of cells showed that the hydrophilic shell significantly affects the micellar stability, localization, cell internalization kinetics, and the cargo release mechanism. Overall, the high molecular precision and the ability of these amphiphiles to report their disassembly, even in complex biological media, allowed us to directly compare the different types of micelles, providing striking insights into how the composition of the micelle shells and cores can affect their properties and potential to serve as nanocarriers

Resting-State Brain Functional Connectivity Is Altered in Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Populations at risk for AD show altered brain activity in the default mode network (DMN) before cognitive dysfunction. We evaluated this brain pattern in T2DM patients. We compared T2DM patients (n = 10, age = 56 ± 2.2 years, fasting plasma glucose [FPG] = 8.4 ± 1.3 mmol/L, HbA1c = 7.5 ± 0.54%) with nondiabetic age-matched control subjects (n = 11, age = 54 ± 1.8 years, FPG = 4.8 ± 0.2 mmol/L) using resting-state functional magnetic resonance imaging to evaluate functional connectivity strength among DMN regions. We also evaluated hippocampal volume, cognition, and insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR). Control subjects showed stronger correlations versus T2DM patients in the DMN between the seed (posterior cingulate) and bilateral middle temporal gyrus (β = 0.67 vs. 0.43), the right inferior and left medial frontal gyri (β = 0.75 vs. 0.54), and the left thalamus (β = 0.59 vs. 0.37), respectively, with no group differences in cognition or hippocampal size. In T2DM patients, HOMA-IR was inversely correlated with functional connectivity in the right inferior frontal gyrus and precuneus. T2DM patients showed reduced functional connectivity in the DMN compared with control subjects, which was associated with insulin resistance in selected brain regions, but there were no group effects of brain structure or cognition

Responsive glyco-poly(2-oxazoline)s: synthesis, cloud point tuning, and lectin binding

A new sugar-substituted 2-oxazoline monomer was prepared using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Its copolymerization with 2-ethyl-2-oxazoline as well as 2-(dec-9-enyl)-2-oxazoline, yielding well-defined copolymers with the possibility to tune the properties by thiol-ene "click" reactions, is described. Extensive solubility studies on the corresponding glycocopolymers demonstrated that the lower critical solution temperature behavior and pH-responsiveness of these copolymers can be adjusted in water and phosphate-buffered saline (PBS) depending on the choice of the thiol. By conjugation of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose and subsequent deprotection of the sugar moieties, the hydrophilicity of the copolymer could be increased significantly, allowing a cloud-point tuning in the physiological range. Furthermore, the binding capability of the glycosylated copoly(2-oxazoline) to concanavalin A was investigated

Patent Politics: Intellectual Property, the Railroad Industry, and the Problem of Monopoly

As winter descended on Washington in December 1878, the Forty-fifth Congress gathered for what promised to be a hectic third and final session. At this critical juncture in American politics, the Senate found itself embroiled in a long and complex discussion of the virtues and deficiencies of the patent system. Patent policy resonated with powerfully felt ideologies and tapped into strongly felt beliefs. Patents were exclusive privileges that the federal government granted to certain individuals for a limited period of time, and, like all monopoly grants, their regulation raised some of the most fundamental questions of the age. The monopoly issue confronted every branch of nineteenth-century American government as well as every jurisdiction: federal, state, and local. In essence, the issue boiled down to two interrelated questions: Did the government have the authority to regulate the monopolies it had created? And, if so, how? The ramifications of the patent issue were practical as well as ideological. At its core, it posed a special challenge for two groups of economic actors, namely, farmers and railroads, who were often at odds not only with Congress but also with each other

Förster resonance energy transfer in fluorophore labeled poly(2-ethyl-2-oxazoline)s†

YesDye-functionalized polymers have been extensively studied to understand polymer chain dynamics, intra or inter-molecular association and conformational changes as well as in practical applications such as signal amplification in diagnostic tests and light-harvesting antennas. In this work, the Förster resonance energy transfer (FRET) of dye-functionalized poly(2-ethyl-2-oxazoline) (PEtOx) was studied to evaluate the effect of dye positioning and polymer chain length on the FRET efficiency. Therefore, both α (initiating terminus)- or ω (terminal chain end)-fluorophore single labeled and dual α,ω-fluorescent dye labeled PEtOx were prepared via cationic ring opening polymerization (CROP) using 1-(bromomethyl)pyrene as the initiator and/or 1-pyrenebutyric acid or coumarin 343 as the terminating agent, yielding well-defined PEtOx with high labeling efficiency (over 91%). Fluorescence studies revealed that intramolecular FRET is most efficient for heterotelechelic PEtOx containing both pyrene and coumarin 343 fluorophores as chain ends, as expected. A strong dependence of the energy transfer on the chain length was found for these dual labeled polymers. The polymers were tested in both dilute organic (chloroform) and aqueous media revealing a higher FRET efficiency in water due to the enhanced emissive properties of pyrene. The application of dual labeled polymers as fluorescent probes for temperature sensing was demonstrated based on the lower critical solution temperature behavior of the PEtOx. Furthermore, these polymers could be successfully processed into fibers and thin films. Importantly, the fluorescence properties were retained in the solid state without decreasing the FRET efficiency, thus opening future possibilities for application of these materials in solar cells and/or sensors