Facile Generation of Heterotelechelic Poly(2-Oxazoline)s Towards Accelerated Exploration of Poly(2-Oxazoline)-Based Nanomedicine.

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation.

Amphiphilic Poly(2-oxazoline)s with Glycine-Containing Hydrophobic Blocks Tailored for Panobinostat- and Imatinib-Loaded Micelles.

Aiming toward the development of tailored carrier materials for the cytostatics panobinostat and imatinib, an amphiphilic block copolymer composed of poly(2-ethyl-2-oxazoline) and a degradable poly(2-(3-phenylpropyl)-2-oxazoline) analogue () was synthesized a postpolymerization synthesis route based on reacylation of oxidized linear poly(ethylene imine). The obtained was found to readily self-assemble into well-defined micelles with a critical micelle concentration of 1 μg mL. The incubation of HUVEC cells with the blank micelles revealed their excellent cytocompatibility (up to 2 mg mL), thus confirming the polymers' suitability for potential drug delivery application.

Non-activated Esters as Reactive Handles in Direct Post-Polymerization Modification.

Non-activated esters are prominently featured functional groups in polymer science, as ester functional monomers display great structural diversity and excellent compatibility with a wide range of polymerization mechanisms. Yet, their direct use as a reactive handle in post-polymerization modification has been typically avoided due to their low reactivity, which impairs the quantitative conversion typically desired in post-polymerization modification reactions. While activated ester approaches are a well-established alternative, the modification of non-activated esters remains a synthetic and economically valuable opportunity.

Poly(-allyl acrylamide) as a Reactive Platform toward Functional Hydrogels.

The synthesis of poly(-allyl acrylamide) (PNAllAm) as a platform for the preparation of functional hydrogels is described. The PNAllAm was synthesized via organocatalyzed amidation of poly(methyl acrylate) (PMA) with allylamine and characterized by H NMR spectroscopy, size exclusion chromatography (SEC), and turbidimetry, which allowed an estimation of the lower critical solution temperature of ∼26 °C in water. The PNAllAm was then used to make functional hydrogels via photoinitiated thiol-ene chemistry, where dithiothreitol (DTT) was used to cross-link the polymer chains.

Stable amorphous solid dispersion of flubendazole with high loading via electrospinning.

In this work, an important step is taken towards the bioavailability improvement of poorly water-soluble drugs, such as flubendazole (Flu), posing a challenge in the current development of many novel oral-administrable therapeutics. Solvent electrospinning of a solution of the drug and poly (2-ethyl-2-oxazoline) (PEtOx) is demonstrated to be a viable strategy to produce stable nanofibrous amorphous solid dispersions (ASDs) with ultrahigh drug-loadings (up to 55 wt% Flu) and long-term stability (at least one year). Importantly, at such high drug loadings, the concentration of the polymer in the electrospinning solution has to be lowered below the concentration where it can be spun in absence of the drug as the interactions between the polymer and the drug result in increased solution viscosity.

Bioresponsive Polymers for Nanomedicine-Expectations and Reality!

Bioresponsive polymers in nanomedicine have been widely perceived to selectively activate the therapeutic function of nanomedicine at diseased or pathological sites, while sparing their healthy counterparts. This idea can be described as an advanced version of Paul Ehrlich's magic bullet concept. From that perspective, the inherent anomalies or malfunction of the pathological sites are generally targeted to allow the selective activation or sensory function of nanomedicine.

Accelerated Post-Polymerization Amidation of Polymers with Side-Chain Ester Groups by Intramolecular Activation.

The catalytic conversion of esters to amides represents new opportunities in the synthetic diversification and upcycling of polymers, as esters are commonly featured in various polymer structures. Yet, direct amidation is typically hampered by poor reaction kinetics and the effects of polymer structure on the reactivity remain poorly understood. We report the accelerated amidation for amines with additional hydrogen bond donating or accepting groups.

Effective mRNA Protection by Poly(l-ornithine) Synergizes with Endosomal Escape Functionality of a Charge-Conversion Polymer toward Maximizing mRNA Introduction Efficiency.

For efficient delivery of messenger (m)RNA, delivery carriers need two major functions: protecting mRNA from nucleases and translocating mRNA from endolysosomes to the cytoplasm. Herein, these two complementary functionalities are integrated into a single polyplex by fine-tuning the catiomer chemical structure and incorporating the endosomal escape modality. The effect of the methylene spacer length on the catiomer side chain is evaluated by comparing poly(l-lysine) (PLL) with a tetramethylene spacer and poly(L-ornithine) (PLO) with a trimethylene spacer.

Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer.

Prevention of metastatic and local-regional recurrence of cancer after surgery remains difficult. Targeting postsurgical premetastatic niche and microresiduals presents an excellent prospective opportunity but is often challenged by poor therapeutic delivery into minimal residual tumors. Here, an enzymatically transformable polymer-based nanotherapeutic approach is presented that exploits matrix metalloproteinase (MMP) overactivation in tumor-associated tissues to guide the codelivery of colchicine (microtubule-disrupting and anti-inflammatory agent) and marimastat (MMP inhibitor).

Poly(2-allylamidopropyl-2-oxazoline)-Based Hydrogels: From Accelerated Gelation Kinetics to Compatibility in a Murine Subdermal Implant Model.

A rapid photo-curing system based on poly(2-ethyl-2-oxazoline--2-allylamidopropyl-2-oxazoline) and its compatibility are presented. The base polymer was synthesized from the copolymerization of 2-ethyl-2-oxazoline (EtOx) and the methyl ester containing 2-methoxycarboxypropyl-2-oxazoline (CMestOx) followed by amidation with allylamine to yield a highly water-soluble macromer. We showed that spherical hydrogels can be obtained by a simple water-in-oil gelation method using thiol-ene coupling and investigated the biocompatibility of these hydrogel spheres in a 28-day murine subdermal model.

Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition.

Smart or adaptive materials often utilize stimuli-responsive polymers, which undergo a phase transition in response to a given stimulus. So far, various stimuli have been used to enable the modulation of drug release profiles, cell-interactive behavior, and optical and mechanical properties. In this respect, molecular recognition is a powerful tool to fine-tune the stimuli-responsive behavior due to its high specificity.

Injectable biocompatible poly(2-oxazoline) hydrogels by strain promoted alkyne-azide cycloaddition.

Poly(2-alkyl-2-oxazoline) (PAOx) hydrogels are tailorable synthetic materials with demonstrated biomedical applications, thanks to their excellent biocompatibility and tunable properties. However, their use as injectable hydrogels is challenging as it requires invasive surgical procedures to insert the formed hydrogel into the body due to their nonsoluble 3D network structures. Herein, we introduce cyclooctyne and azide functional side chains to poly(2-oxazoline) copolymers to induce in situ gelation using strain promoted alkyne-azide cycloaddition.

Stoichiometric Control over Partial Transesterification of Polyacrylate Homopolymers as Platform for Functional Copolyacrylates.

Only recently, post-polymerization modification reactions of unactivated polyacrylates have been emerging as an attractive alternative to utilizing reactive monomers, enabling the synthetic upcycling of these widely applied polymers. Within this contribution, the triazabicyclodecene-catalyzed transesterification of polyacrylates is reported, including the reaction kinetics and the broad scope for macromolecular design of functional copolyacrylates. More specifically, the transesterification is performed under equilibrium conditions with a set of primary alcohols whereby the reaction kinetics and the obtained conversion as a function of stoichiometric excess of alcohol are evaluated.

Poly(2-ethyl-2-oxazoline) Conjugates with Salicylic Acid via Degradable Modular Ester Linkages.

Conjugation of drugs to polymers is a widely used approach to gain control over the release of therapeutics. In this contribution, salicylic acid, a multipurpose model drug, is conjugated to the biocompatible poly(2-ethyl-2-oxazoline) (PEtOx). The drug is attached to the side chains of a polymer carrier through a hydrolytically cleavable ester linker, via a sequential postpolymerization modification.

Water-Stable Plasma-Polymerized ,-Dimethylacrylamide Coatings to Control Cellular Adhesion.

The plasma polymerization of amide-based precursors is a nearly unexplored research area, which is in contrast with the abundance of reports focusing on amide-based surface modification using wet chemistry. Therefore, this study aims to profoundly investigate the near-atmospheric pressure plasma polymerization of ,-dimethylacrylamide (DMAM) to obtain stable coatings. In contrast to the unstable coatings obtained at lower discharge powers, the stable coatings that were obtained at higher powers showed a lower hydrophilicity as assessed by water contact angle (WCA).

Metal Ion Selective Self-Assembly of a Ligand Functionalized Polymer into [1+1] Macrocyclic and Supramolecular Polymer Structures via Metal-Ligand Coordination.

The design and synthesis of polymer-based metallomacrocycles relying on metal-ligand interactions remain a challenge in the polymer field. Instead of utilizing chemical reactions to synthesize macrocycles, a general approach is proposed to construct metallomacrocyclic structures through supramolecular self-assembly of a specific macroligand with suitable transition metal ions. Therefore, a new ditopic macroligand (L) consisting of PEG end-capped with 2,6-bis(1,2,3-triazol-4-yl)pyridine derivatives is prepared via CuAAC "click" reaction.

Influence of the Aliphatic Side Chain on the Near Atmospheric Pressure Plasma Polymerization of 2-Alkyl-2-oxazolines for Biomedical Applications.

Plasma polymerization is gaining popularity as a technique for coating surfaces due to the low cost, ease of operation, and substrate-independent nature. Recently, the plasma polymerization (or deposition) of 2-oxazoline monomers was reported resulting in coatings that have potential applications in regenerative medicine. Despite the structural versatility of 2-oxazolines, only a few monomers have been subjected to plasma polymerization.

Striking Effect of Polymer End-Group on C Nanoparticle Formation by High Shear Vibrational Milling with Alkyne-Functionalized Poly(2-oxazoline)s.

Buckminsterfullerene (C) has a large potential for biomedical applications. However, the main challenge for the realization of its biomedical application potential is to overcome its extremely low water solubility. One approach is the coformulation with biocompatible water-soluble polymers, such as poly(2-oxazoline)s (PAOx), to form water-soluble C nanoparticles (NPs).

The Elusive Seven-Membered Cyclic Imino Ether Tetrahydrooxazepine.

Cyclic imino ether heterocycles are used as ligands in transition metal catalysis, in various drugs and as reactive monomers in living cationic ring-opening polymerization (CROP). While five- and six-membered cyclic imino ethers, i.e.

Fabrication of PEOT/PBT Nanofibers by Atmospheric Pressure Plasma Jet Treatment of Electrospinning Solutions for Tissue Engineering.

This study focuses on the enhanced electrospinning of 300-Polyethylene oxide-polyethylene oxide terephthalate/polybutylene terephthalate (PEOT/PBT). An atmospheric pressure plasma jet for liquid treatment is applied to a solution with 9 w/v% PEOT/PBT dissolved in either chloroform (CHCl ), CHCl  + N,N-dimethylformamide (DMF), CHCl  + methanol (MeOH), or CHCl  + hexafluoroisopropanol (HFIP). For all conditions, the plasma-treated samples present better-quality fibers: less or no-beads and uniform fiber diameter distribution.

Effects of a dielectric barrier discharge (DBD) treatment on chitosan/polyethylene oxide nanofibers and their cellular interactions.

In this study, chitosan (CS)/polyethylene oxide (PEO) nanofibrous mats (Ø: 166 ± 43 nm) were fabricated by electrospinning and subsequently surface-modified by a dielectric barrier discharge (DBD) sustained in argon, ammonia/helium or nitrogen. The surface properties of the CS/PEO nanofibers (NFs) before and after plasma treatment were characterized using contact angle measurements, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Additionally, the mechanical properties and PEO leaching in aqueous conditions of the different NFs under study were examined by tensile tests and nuclear magnetic resonance (H NMR) spectroscopy respectively.

Mechanochemical Preparation of Stable Sub-100 nm γ-Cyclodextrin:Buckminsterfullerene (C60) Nanoparticles by Electrostatic or Steric Stabilization.

Buckminster fullerene (C )'s main hurdle to enter the field of biomedicine is its low bioavailability, which results from its extremely low water solubility. A well-known approach to increase the water solubility of C is by complexation with γ-cyclodextrins. However, the formed complexes are not stable in time as they rapidly aggregate and eventually precipitate due to attractive intermolecular forces, a common problem in inclusion complexes of cyclodextrins.

Atmospheric Pressure Plasma Jet Treatment of Poly-ε-caprolactone Polymer Solutions To Improve Electrospinning.

An atmospheric pressure plasma jet (APPJ) specifically designed for liquid treatment has been used in this work to improve the electrospinnability of a 5 w/v % solution of poly-ε-caprolactone (PCL) in a mixture of chloroform and N,N-dimethylformamide. Untreated PCL solutions were found to result in nonuniform fibers containing a large number of beads, whereas plasma-treated solutions (exposure time of 2-5 min) enabled the generation of beadless, uniform nanofibers with an average diameter of 450 nm. This enhanced electrospinnability was found to be mainly due to the highly increased conductivity of the plasma-modified PCL solutions.