Reactive-Oxygen-Species-Responsive Drug Delivery Systems: Promises and Challenges

Given the increasing evidence indicates that many pathological conditions are associated with elevated reactive oxygen species (ROS) levels, there have been growing research efforts focused on the development of ROS-responsive carrier systems because of their promising potential to realize more specific diagnosis and effective therapy. By judicious utilization of ROS-responsive functional moieties, a wide range of carrier systems has been designed for ROS-mediated drug delivery. In this review article, insights into design principle and recent advances on the development of ROS-responsive carrier systems for drug delivery applications are provided alongside discussion of their in vitro and in vivo evaluation. In particular, the discussions in this article will mainly focus on polymeric nanoparticles, hydrogels, inorganic nanoparticles, and activatable prodrugs that have been integrated with diverse ROS-responsive moieties for spatiotemporally controlled release of drugs for effective therapy.1149sciescopu

Biocompatibility of implantable materials: an oxidative stress viewpoint

Oxidative stress occurs when the production of oxidants surpasses the antioxidant capacity in living cells. Oxidative stress is implicated in a number of pathological conditions such as cardiovascular and neurodegenerative diseases but it also has crucial roles in the regulation of cellular activities. Over the last few decades, many studies have identified significant connections between oxidative stress, inflammation and healing. In particular, increasing evidence indicates that the production of oxidants and the cellular response to oxidative stress are intricately connected to the fate of implanted biomaterials. This review article provides an overview of the major mechanisms underlying the link between oxidative stress and the biocompatibility of biomaterials. ROS, RNS and lipid peroxidation products act as chemo-attractants, signalling molecules and agents of degradation during the inflammation and healing phases. As chemo-attractants and signalling molecules, they contribute to the recruitment and activation of inflammatory and healing cells, which in turn produce more oxidants. As agents of degradation, they contribute to the maturation of the extracellular matrix at the healing site and to the degradation of the implanted material. Oxidative stress is itself influenced by the material properties, such as by their composition, their surface properties and their degradation products. Because both cells and materials produce and react with oxidants, oxidative stress may be the most direct route mediating the communication between cells and materials. Improved understanding of the oxidative stress mechanisms following biomaterial implantation may therefore help the development of new biomaterials with enhanced biocompatibility

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Non-polar semifluorinated amphiphiles,synthesis-nanostructuration in 2D and 3D

Ce travail de thèse s'inscrit dans le domaine des molécules amphiphiles semi-fluorées et s'étend de la synthèse de nouvelles architectures à l'investigation de leurs propriétés d'auto-assemblage à 2D et à 3D. Il s'articule principalement autour de l'élaboration et de l'étude de films fins obtenus par auto-assemblage d'amphiphiles semi-fluorés, avec pour objectif de créer des surfaces décorées par des nanodomaines de tailles et formes contrôlées. La première partie de ce travail analyse la compression de nano-objets auto-assemblés constitués de diblocs FnHm(F(CF2)n(CH2)mH), conduisant à la formation de films composites à plusieurs niveaux de structuration à l'échelle nanométrique (développement d'une bicouche (F8H20) ou d'inflorescences (Fl0H16) au dessus du tapis de micelles). La deuxième partie est consacrée à la synthèse et à l'étude du comportement d'une nouvelle famille de tétrablocs semi-fluorés (CnF2n+1CH2)(Cm-2H2m3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3), di(FnHm) . Ils présentent une transition réversible du 1er ordre avant la fusion entre une phase modulée ruban et une phase lamellaire de type hexatique B. L'imagerie de la surface (à l'échelle du nanomètre par AFM), sur films transférés (ou obtenus par spin-coating) révèle qu'ils s'auto-assemblent en micelles de surface dont la compression engendre la formation d'une seconde couche superposée, elle-même composée de micelles de surface. Dans une dernière partie, une nouvelle famille d'amphiphiles triaffines FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx = CH3(OC2H4)xO) récemment synthétisée au sein de l'équipe, a fait l'objet d'une étude de leur aptitude à la nanostructuration à l'interface eau/air (2D) et dans l'eau (3D).This work deals with semifluorinated amphiphiles, from the synthesis of new architectures to the investigation of their self-assembly in 2D and 3D. It is principally based on the elaboration and study of thin films obtained by self-assembly of semifluorinated alkanes in order to create surfaces decorated with nanodomains weIl defined in size and shape. The first part of this work analyses the compression of self assembled nanometric objects constituted by FnHm diblocks (F(CF2)n(CH2)mH), leading to hitherto unknown organized nanometric composite arrangements (bilayer (FBH20) or crystalline like-inflorescences (Fl0H16) in coexistence with the initial monolayer of micelles). The second part is dedicated to the synthesis and the study of the behavior of a new familly of semifluorinated tetrablocks, di(FnHm) (CnF2n+1CH2)(Cm-2H2m-3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3).They present a reversible first order transition before melting, between a modulated smectic phase and a lamellar hexatic B arrangement. As assessed by AFM, transferred or spin-coated films consist of two sublayers of dis crete surface micelles. In the last part, the nanostructuration at the air /water interface and in water of a new triaffine architecture FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx= CH3(OC2H4)xO) was investigated

Non-polar semifluorinated amphiphiles,synthesis-nanostructuration in 2D and 3D

Ce travail de thèse s'inscrit dans le domaine des molécules amphiphiles semi-fluorées et s'étend de la synthèse de nouvelles architectures à l'investigation de leurs propriétés d'auto-assemblage à 2D et à 3D. Il s'articule principalement autour de l'élaboThis work deals with semifluorinated amphiphiles, from the synthesis of new architectures to the investigation of their self-assembly in 2D and 3D. It is principally based on the elaboration and study of thin films obtained by self-assembly of semifluori

Amphiphiles semi-fluorés non-polaires (Synthèse-nanostructuration d espaces à 2D et 3D)

Ce travail de thèse s'inscrit dans le domaine des molécules amphiphiles semi-fluorées et s'étend de la synthèse de nouvelles architectures à l'investigation de leurs propriétés d'auto-assemblage à 2D et à 3D. Il s'articule principalement autour de l'élaboration et de l'étude de films fins obtenus par auto-assemblage d'amphiphiles semi-fluorés, avec pour objectif de créer des surfaces décorées par des nanodomaines de tailles et formes contrôlées. La première partie de ce travail analyse la compression de nano-objets auto-assemblés constitués de diblocs FnHm(F(CF2)n(CH2)mH), conduisant à la formation de films composites à plusieurs niveaux de structuration à l'échelle nanométrique (développement d'une bicouche (F8H20) ou d'inflorescences (Fl0H16) au dessus du tapis de micelles). La deuxième partie est consacrée à la synthèse et à l'étude du comportement d'une nouvelle famille de tétrablocs semi-fluorés (CnF2n+1CH2)(Cm-2H2m3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3), di(FnHm) . Ils présentent une transition réversible du 1er ordre avant la fusion entre une phase modulée ruban et une phase lamellaire de type hexatique B. L'imagerie de la surface (à l'échelle du nanomètre par AFM), sur films transférés (ou obtenus par spin-coating) révèle qu'ils s'auto-assemblent en micelles de surface dont la compression engendre la formation d'une seconde couche superposée, elle-même composée de micelles de surface. Dans une dernière partie, une nouvelle famille d'amphiphiles triaffines FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx = CH3(OC2H4)xO) récemment synthétisée au sein de l'équipe, a fait l'objet d'une étude de leur aptitude à la nanostructuration à l'interface eau/air (2D) et dans l'eau (3D).This work deals with semifluorinated amphiphiles, from the synthesis of new architectures to the investigation of their self-assembly in 2D and 3D. It is principally based on the elaboration and study of thin films obtained by self-assembly of semifluorinated alkanes in order to create surfaces decorated with nanodomains weIl defined in size and shape. The first part of this work analyses the compression of self assembled nanometric objects constituted by FnHm diblocks (F(CF2)n(CH2)mH), leading to hitherto unknown organized nanometric composite arrangements (bilayer (FBH20) or crystalline like-inflorescences (Fl0H16) in coexistence with the initial monolayer of micelles). The second part is dedicated to the synthesis and the study of the behavior of a new familly of semifluorinated tetrablocks, di(FnHm) (CnF2n+1CH2)(Cm-2H2m-3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3).They present a reversible first order transition before melting, between a modulated smectic phase and a lamellar hexatic B arrangement. As assessed by AFM, transferred or spin-coated films consist of two sublayers of dis crete surface micelles. In the last part, the nanostructuration at the air /water interface and in water of a new triaffine architecture FnHmEOx (Fn = CnF2n+1;Hm = CmH2m+1;EOx= CH3(OC2H4)xO) was investigated.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Thermal Behavior and High- and Low-Temperature Phase Structures of Gemini Fluorocarbon/Hydrocarbon Diblocks

The thermal behavior and phase structure of two series of gemini fluorocarbon/hydrocarbon diblock amphiphiles with the general formula (C_<i>n</i>F_2<i>n</i>+1CH₂)­(C_{<i>m</i> – 2}H_{2<i>m</i> – 3})­CH–CH­(C_<i>n</i>F_2<i>n</i>+1CH₂)­(C_{<i>m</i> – 2}H_{2<i>m</i> – 3}), with <i>n</i> = 8, 10 and <i>m</i> = 6, 12, 14, 16, 18, 20 (abbreviated as di­(<i>FnHm</i>)), have been investigated by differential scanning calorimetry, polarized optical and freeze–fracture transmission electron microscopies, dilatometry, and small-angle X-ray scattering (SAXS). The various terms of the series exhibit the same thermal behavior, essentially composed of two exothermal transitions, a low-temperature event that corresponds to the melting of the hydrocarbon chains at <i>T</i>_H and a high-temperature transition associated with the melting of the fluorocarbon chains at <i>T</i>_F. Below <i>T</i>_H, a disordered plastic rotator phase, M_LT, and above <i>T</i>_H, a lamellar phase, M_HT, were determined by SAXS experiments. Above <i>T</i>_F, the compounds eventually clear into the isotropic liquid. In the M_HT phase, both the <i>Fn</i> and <i>Hm</i> blocks are segregated from each other, forming sublayers with sharp interfaces, as revealed by the five lamellar orders and remarkable sharpness of the SAXS peaks. In the M_LT phase, the partial crystallization of the aliphatic blocks when the temperature is lowered leads to the disruption of the aliphatic sublayers into rows of ribbons arranged according to pseudohexagonal and/or rectangular arrangements with different lattice sizes (<i>p</i>2<i>gg</i> symmetry). The <i>Fn</i> segments form the fluorinated continuum. In support of SAXS, molecular packing models of the tetrablocks are proposed on the basis of the temperature/volume variations of di­(<i>F</i>10<i>H</i>20) and di­(<i>F</i>10<i>H</i>16) in both high- and low-temperature phases, as determined by dilatometry. It is notable that the arrangements found for di­(<i>FnHm</i>) are completely different from those previously reported for <i>FnHm</i> diblocks, revealing the influence of the linker unit on the solid-state behavior of the tetrablocks