Copper-mediated living radical polymerisation of acrylates and acrylamides : utilising light as an external stimuli

The main focus of this thesis is to expand the scope of the newly developed copper-mediated photo-induced reversible deactivation radical polymerisation (RDRP) system. The synthesis of α,ω-telechelic multiblock copolymers will be attempted utilising a wide range of bi-functional initiators and acrylic monomers targeting different chain lengths. The compatibility of this system with special solvents and catalysts will also be investigated. Moreover, the limitations of this technique will be highlighted including the necessity to employ various components that require multiple optimisation studies and the challenge in efficiently storing many reactants (e.g. ligands, copper catalyst). Two novel discrete complexes that incorporate both precatalyst and ligand will be synthesised to address the aforementioned issues while advanced characteristics and advantages over the previous approach will be demonstrated. In the second part the polymerisation of acrylamides will be demonstrated utilising aqueous Cu(0)-mediated RDRP since the light system is not applicable for the controlled polymerisation of this monomeric family. The high end-group fidelity of the resulted polyacrylamides will also be exemplified via sequential monomer addition with both acrylamide and acrylate monomers, yielding well-defined hydrophilic materials. In the last chapter the synthesis of semifluorinated triblock copolymers in a multigram scale utilising the photo-induced RDRP will be demonstrated. This is an ongoing work with the Lubrizol Corporation and constitutes only a few initial studies towards developing materials with interesting properties or applications and basically sets the scene for future work

Transdermal delivery of ibuprofen utilizing a novel solvent free pressure sensitive adhesive (PSA) : TEPI® technology

Purpose The main objective of this present study was the investigation of potential novel transdermal patch technology (TEPI®) delivering ibuprofen as the active pharmaceutical ingredient (API) using a novel poly(ether-urethane)-silicone crosslinked pressure-sensitive adhesive (PSA) as the drug reservoir in a solvent-free manufacturing process. Methods The patch was synthesized utilizing the hot-melt crosslinking technique without the addition of solvents at 80 °C in 100% relative humidity. Dissolution and permeation studies performed utilizing diffusion cells and subsequently HPLC validated methods were employed to determine the API content in the acceptor solution. Accelerated stability studies were also performed at 40 °C and 70% relative humidity. The adhesive performance of the fabricated patch was evaluated utilizing loop tack adhesion tests. Results In vitro permeation experiments across both Strat-M® and human skin demonstrated that ibuprofen can easily be released from the adhesive matrix and penetrate through the studied membrane. A comparison on the permeation rates of the API across the two membranes indicated that there is not a strong correlation between the obtained data. The presence of chemical enhancers facilitated an increased flux of the API higher than observed in the basic formulation. Initial stability studies of the optimized formulation showed no degradation with respect to the drug content. Adhesion studies were also performed indicating higher values when compared with commercially available products. Conclusions The present study demonstrated the fabrication of an ibuprofen patch utilizing a versatile, solvent-free drug delivery platform. Upon optimization of the final system, the resulting patch offers many advantages compared to commercially available formulations including high drug loading (up to 25 wt%), good adhesion, and painless removal leaving no residues on the skin. This PSA offers many advantages over existing adhesive technology

Polymerisation of 2-acrylamido-2-methylpropane sulfonic acid sodium salt (NaAMPS) and acryloyl phosphatidylcholine (APC) via aqueous Cu(0)-mediated radical polymerisation

The scope of aqueous Cu(0)-mediated living radical polymerisation has been expanded with the preparation of poly(2-acrylamido-2-methylpropane sulfonic acid sodium salt (P(NaAMPS)) and poly(acryloyl phosphatidycholine) (PAPC). Manipulation of the reaction conditions furnishes polymers capable of undergoing chain extension and supporting the synthesis of block copolymers at 0 °C

Methacrylic block copolymers by sulfur free RAFT (SF RAFT) free radical emulsion polymerisation

We demonstrate the use of sulfur free reversible addition-fragmentation chain transfer polymerisation (RAFT as a versatile tool for the controlled synthesis of methacrylic block and comb-like copolymers. Sulfur free RAFT (SF-RAFT) utilises vinyl terminated macromonomers obtained via catalytic chain transfer polymerisation (CCTP) of methacrylates as a chain transfer agent (CTA), and thus precluding adverse aspects of the RAFT such as toxicity of dithioesters. We have synthesised a range of narrow dispersity block copolymers (Đ < 1.2) and comb-like macromolecules by employing emulsion polymerisation allowing for the preparation of relatively large quantities (~50 g) of the above mentioned copolymers promptly and straightforwardly. Copolymers were characterised using 1H NMR, size exclusion chromatography (SEC), thermogravimetric analysis (TGA) and matrix-assisted laser desorption/ionization time of flight mass spectroscopy (MALDI-TOF-MS) techniques

Controlled aqueous polymerization of acrylamides and acrylates and “in situ” depolymerization in the presence of dissolved CO2

Aqueous copper-mediated radical polymerization of acrylamides and acrylates in carbonated water resulted in high monomer conversions (t t > 10 min). The regenerated monomer was characterized and repolymerized following deoxygenation of the resulting solutions to reyield polymers in high conversions that exhibit low dispersities

Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis

Tumor progression locus-2 (Tpl2) kinase is a major inflammatory mediator in immune cell types recently found to be genetically associated with inflammatory bowel diseases (IBDs). Here we show that Tpl2 may exert a dominant homeostatic rather than inflammatory function in the intestine mediated specifically by subepithelial intestinal myofibroblasts (IMFs). Mice with complete or IMF-specific Tpl2 ablation are highly susceptible to epithelial injury-induced colitis showing impaired compensatory proliferation in crypts and extensive ulcerations without significant changes in inflammatory responses. Following epithelial injury, IMFs sense innate or inflammatory signals and activate, via Tpl2, the cyclooxygenase-2 (Cox-2)- prostaglandin E2 (PGE2) pathway, which we show here to be essential for the epithelial homeostatic response. Exogenous PGE2 administration rescues mice with complete or IMF-specific Tpl2 ablation from defects in crypt function and susceptibility to colitis. We also show that Tpl2 expression is decreased in IMFs isolated from the inflamed ileum of IBD patients indicating that Tpl2 function in IMFs may be highly relevant to human disease. The IMF-mediated mechanism we propose also involves the IBD-associated genes IL1R1, MAPK1, and the PGE2 receptor-encoding PTGER4. Our results establish a previously unidentified myofibroblast-specific innate pathway that regulates intestinal homeostasis and may underlie IBD susceptibility in humans

Absolut “copper catalyzation perfected”; robust living polymerization of NIPAM : Guinness is good for SET-LRP

The controlled polymerization of N-isopropyl acrylamide (NIPAM) is reported in a range of international beers, wine, ciders and spirits utilizing Cu(0)-mediated living radical polymerization (SET-LRP). Highly active Cu(0) is first formed in situ by the rapid disproportionation of [Cu(I)(Me6-Tren)Br] in the commercial water–alcohol mixtures. Rapid, yet highly controlled, radical polymerization follows (Đ values as low as 1.05) despite the numerous chemicals of diverse functionality present in these solvents e.g. alpha acids, sugars, phenols, terpenoids, flavonoids, tannins, metallo-complexes, anethole etc. The results herein demonstrate the robust nature of the aqueous SET-LRP protocol, underlining its ability to operate efficiently in a wide range of complex chemical environments

The Impact of Immune Checkpoint Inhibitors-Induced Skin Toxicity on Patients’ Quality of Life and the Role of Dermatologic Intervention

Introduction: Data regarding quality of life (QoL) of oncologic patients experiencing dermatologic immune-related adverse events (dirAEs)and their course after dermatologic intervention are scarce. Objectives To assess the impact of dirAEs on patients' QoL and to investigate the correlation between dermatologic and oncologic indexes used for estimating QoL. Methods We enrolled oncologic patients with dirAEs managed in two supportive oncodermatology outpatient clinics in Greece. Patient-reported outcomes included DLQI, EORTC-QLQ-C30 and Numerical Rating Scale for pruritus (pNRS). Results Overall, 110 patients were enrolled in the study. Mean(SD) DLQI and pNRS scores were 15.54 (5.44) and7.25 (2.95), correspondingly, while functional, symptom and summary scores of EORTC-C30 were 79.17 (2.11), 17.66 (3.60) and 80.67 (3.08), respectively. After therapeutic interventions, there was a statistically significant decrease in DLQI scores after1st intervention compared to baseline, and 2nd intervention compared to 1st [mean (SD) decrease 4.38 (2.91), p<0.001 and 5.16 (3.99), p<0.001, respectively]. DLQI showed no correlation with global health status/QoLs (rho 0.01, p=0.90) of EORTC-C30. Conclusions dirAEs negatively affect QoL. Dermatologic intervention improves patients’ QoL, facilitating an unimpaired oncologic treatment. Poor correlation between DLQI and EORTC-QLQ-30 highlights the need for adapted QoL measurement tools in the context of ICIs treatment. 

How to develop a national heart failure clinics network: a consensus document of the Hellenic Heart Failure Association

Heart failure (HF) is rapidly growing, conferring considerable mortality, morbidity, and costs. Dedicated HF clinics improve patient outcomes, and the development of a national HF clinics network aims at addressing this need at national level. Such a network should respect the existing health care infrastructures, and according to the capacities of hosting facilities, it can be organized into three levels. Establishing the continuous communication and interaction among the components of the network is crucial, while supportive actions that can enhance its efficiency include involvement of multidisciplinary health care professionals, use of structured HF-specific documents, such as discharge notes, patient information leaflets, and patient booklets, and implementation of an HF-specific electronic health care record and database platform