Στατιστικά αμφίφιλα τριπολυμερή αποκρινόμενα σε pH και θερμοκρασία με πολυμερισμό RAFT: Σύνθεση, ιδιότητες αυτο-οργάνωσης σε υδατικά διαλύματα και εγκλωβισμός φαρμάκων

Τα αμφίφιλα στατιστικά συμπολυμερή παρουσιάζουν ιδιαίτερο ενδιαφέρον λόγω της ικανότητάς τους να αυτο-οργανώνονται σε νανοδομές όταν βρεθούν σε υδατικά διαλύματα, ιδιότητα που τα καθιστά ελκυστικά σε βιομηχανικό επίπεδο και πολύ χρήσιμα ως μεταφορείς φαρμάκων και για εφαρμογές σε γονιδιακή θεραπεία. Η συγκεκριμένη μελέτη αφορά στη σύνθεση πέντε στατιστικών τριπολυμερών του τύπου πολυ(μεθακρυλικός εστέρας της διμεθυλαμινοαιθανόλης – co – μεθακρυλικός εστέρας της δωδεκανόλης – co – μεθακρυλικός εστέρας της ολιγοαιθυλενογλυκόλης) διαφορετικής σύστασης, με τη μέθοδο ελεγχόμενου ριζικού πολυμερισμού RAFT. Ακολούθησε ο μοριακός χαρακτηρισμός των συμπολυμερών με χρωματογραφία αποκλεισμού μεγεθών (SEC) για τον προσδιορισμό μοριακών βαρών και κατανομών μοριακών βαρών και με φασματοσκοπικές μεθόδους 1H-NMR και FTIR, προκειμένου να γίνει προσδιορισμός της σύστασης και ταυτοποίηση των χαρακτηριστικών ομάδων των συμπολυμερών. Οι ιδιότητες της αυτο-οργάνωσής τους μελετήθηκαν σαν συνάρτηση μεταβολών στο pH, στη θερμοκρασία και στην ιοντική ισχύ, με τη χρήση μεθόδων δυναμικής σκέδασης φωτός (DLS) και φθορισμομετρίας (FS). Σε επόμενο στάδιο, παρασκευάστηκαν υδατικά διαλύματα των συμπολυμερών και έγινε εγκλωβισμός κουρκουμίνης ως υδρόφοβο φάρμακο στον υδρόφοβο πυρήνα τους. Μελετήθηκαν με τεχνικές δυναμικής σκέδασης φωτός (DLS), φασματοσκοπίας φθορισμού (FS) και υπεριώδους – ορατού (UV-Vis) όσον αφορά τη δομή και τις ιδιότητες των σχηματιζόμενων συσσωματωμάτων. Τέλος, μελετήθηκαν τα συστήματα πολυμερούς-κουρκουμίνης και ως προς την αλληλεπίδραση με πρωτεΐνες του ορού εμβρύου βοοειδούς (FBS), μέσω δυναμικής σκέδασης φωτός (DLS), ως προς τη σταθερότητά τους σε βιολογικά μέσα.Amphiphilic statistical copolymers are of great interest due to their ability to self-assemble into nanoparticles when inserted in aqueous media, which makes them particularly attractive at industrial level and very useful as drug and gene carriers. The current study is about the synthesis of five statistical terpolymers, of the type poly(2-dimethylamino ethyl methacrylate – co – lauryl methacrylate – co – oligo ethyl methacrylate) having different compositions via RAFT polymerization. The synthesis was followed by the molecular characterization of the terpolymers via size exclusion chromatography (SEC) for the determination of molecular weights and the molecular weight distribution and spectroscopic characterization techniques such as 1H-NMR and FTIR, in order to identify the composition of the terpolymers and the feature groups. Their self-assembling behavior was studied as well under the effect of different pH, temperature and ionic strength changes, using dynamic light scattering and fluorescence spectroscopy (FS). Aqueous solutions of the terpolymers were prepared and curcumin was encapsulated as a hydrophobic drug into the hydrophobic domain of the aggregates formed. These aggregates were studied by dynamic light scattering (DLS), fluorescence spectroscopy (FS) and ultraviolet – visible spectroscopy (UV-Vis). Finally, the polymer-curcumin complexes were studied for their interaction with proteins of fetal bovine serum (FBS) via dynamic light scattering (DLS)

Dual-Responsive Amphiphilic P(DMAEMA-co-LMA-co-OEGMA) Terpolymer Nano-Assemblies in Aqueous Media

This work reports on the synthesis and self-assembly of a novel series of dual-responsive poly[2-(dimethylamino)ethylmethacrylate-co-laurylmethacrylate-co-(oligoethyleneglycol)methacrylate], P(DMAEMA-co-LMA-co-OEGMA)statistical terpolymers in aqueous solutions. Five P(DMAEMA-co-LMA-co-OEGMA) amphiphilic terpolymers, having different content of the three monomers, were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The success of the synthesis was confirmed by the molecular characterization of the terpolymers via size exclusion chromatography (SEC) for the determination of molecular weights and the molecular weight distributions. By using nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared (FTIR) spectroscopy, it was possible to determine the exact composition of the terpolymers. Dynamic light scattering (DLS) and fluorescence spectroscopy (FS) indicated the formation of P(DMAEMA-co-LMA-co-OEGMA) unimolecular or multichain aggregates in aqueous solutions, as a response to pH, temperature and ionic strength changes, with their dimensions being largely affected. The amphiphilic terpolymers were able to encapsulate the hydrophobic drug curcumin (CUR) and demonstrate stability to fetal bovine serum (FBS) solutions. These terpolymer aggregates were studied by DLS, FS and UV-Vis, and it was found that they may have been used as potential nanocarriers for drug delivery and bio-imaging applications

Dielectric response of vulcanized natural rubber containing BaTiO3 filler: the role of particle functionalization

Natural rubber (NR) nanocomposites have been prepared with hydroxylated barium titanate filler (BaTiO3-OH), employing emulsion polymerization followed by vulcanization process. The addition of barium titanate, a compound with high dielectric permittivity, was envisaged to increase the insulating properties of NR films, thereby reducing the electrical stress and the possibility of undesired arcing on their surfaces. The content of perovskite particles greatly affected both, the mechanical and the electrical properties, of the vulcanized films. It was observed that the optimum functionalized nanoparticle concentration is around 0.25–0.50 phr, range in which the elongation of break was maintained between 874–935% and the tensile strength was between 4.40–4.80 MPa; whereas the dielectric permittivity (¿') is slightly lower than the pristine NR or the NR compounded with high content of BaTiO3 nanoparticles. The dielectric study revealed the presence of two dielectric relaxation modes: (i) glass to rubber transition (a-relaxation) and (ii) interfacial polarization (IP), known as Maxwell-Wagner-Sillars (MWS) polarization. The comparison between small concentrations of non-functionalized and functionalized BaTiO3 inside NR polymeric films lead to the conclusion that the dielectric breakdown strength is high for non-functionalized fillers, supposedly due to less IP polarization phenomena.Postprint (author's final draft

Dielectric response of vulcanized natural rubber containing BaTiO3 filler: the role of particle functionalization

Natural rubber (NR) nanocomposites have been prepared with hydroxylated barium titanate filler (BaTiO3-OH), employing emulsion polymerization followed by vulcanization process. The addition of barium titanate, a compound with high dielectric permittivity, was envisaged to increase the insulating properties of NR films, thereby reducing the electrical stress and the possibility of undesired arcing on their surfaces. The content of perovskite particles greatly affected both, the mechanical and the electrical properties, of the vulcanized films. It was observed that the optimum functionalized nanoparticle concentration is around 0.25–0.50 phr, range in which the elongation of break was maintained between 874–935% and the tensile strength was between 4.40–4.80 MPa; whereas the dielectric permittivity (¿') is slightly lower than the pristine NR or the NR compounded with high content of BaTiO3 nanoparticles. The dielectric study revealed the presence of two dielectric relaxation modes: (i) glass to rubber transition (a-relaxation) and (ii) interfacial polarization (IP), known as Maxwell-Wagner-Sillars (MWS) polarization. The comparison between small concentrations of non-functionalized and functionalized BaTiO3 inside NR polymeric films lead to the conclusion that the dielectric breakdown strength is high for non-functionalized fillers, supposedly due to less IP polarization phenomena

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)