Development of nanostructured hydrogel for spatial and temporal controlled release of active compounds

L’utilisation de nanovecteurs pour la livraison contrôlée de principes actifs est un concept commun de nous jours. Les systèmes de livraison actuels présentent encore cependant des limites au niveau du taux de relargage des principes actifs ainsi que de la stabilité des transporteurs. Les systèmes composés à la fois de nanovecteurs (liposomes, microgels et nanogels) et d’hydrogels peuvent cependant permettre de résoudre ces problèmes. Dans cette étude, nous avons développé un système de livraison contrôlé se basant sur l’incorporation d’un nanovecteur dans une matrice hydrogel dans le but de combler les lacunes des systèmes se basant sur un vecteur uniquement. Une telle combinaison pourrait permettre un contrôle accru du relargage par stabilisation réciproque. Plus spécifiquement, nous avons développé un hydrogel structuré intégrant des liposomes, microgels et nanogels séparément chargés en principes actifs modèles potentiellement relargués de manière contrôlé. Ce contrôle a été obtenu par la modification de différents paramètres tels que la température ainsi que la composition et la concentration en nanovecteurs. Nous avons comparé la capacité de chargement et la cinétique de relargage de la sulforhodamine B et de la rhodamine 6G en utilisant des liposomes de DOPC et DPPC à différents ratios, des nanogels de chitosan/acide hyaluronique et des microgels de N-isopropylacrylamide (NIPAM) à différents ratios d’acide méthacrylique, incorporés dans un hydrogel modèle d’acrylamide. Les liposomes présentaient des capacités de chargement modérés avec un relargage prolongé sur plus de dix jours alors que les nanogels présentaient des capacités de chargement plus élevées mais une cinétique de relargage plus rapide avec un épuisement de la cargaison en deux jours. Comparativement, les microgels relarguaient complétement leur contenu en un jour. Malgré une cinétique de relargage plus rapide, les microgels ont démontré la possibilité de contrôler finement le chargement en principe actif. Ce contrôle peut être atteint par la modification des propriétés structurelles ou en changeant le milieu d’incubation, comme l’a montré la corrélation avec les isothermes de Langmuir. Chaque système développé a démontré un potentiel contrôle du taux de relargage, ce qui en fait des candidats pour des investigations futures.

Mise au point de complexes liposome/polymère sensibles au pH pour la vectorisation d'agents anticancéreux

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Soil Stabilization with Lime Fly Ash, Iowa Highway Research Board Bulletin No. 26, 1961

The sixth in a series, this bulletin further compiles the reports on completed research done for the Iowa State Highway Research Board under its Project HR-1, The loess and glacial till materials of Iowa; an investigation of their physical and chemical properties and techniques for processing them to increase their all-weather stability for road construction. The research, started in 1950, has been conducted by the Iowa Engineering Experiment Station at Iowa State University under its Project 283-S.

Soil Stabilization with Cement, Iowa Highway Research Board Bulletin No. 23, 1961

This is the fourth publication in a series of compilations of the reports on research completed for the Iowa State Highway Commission. This research was done for the Iowa State Highway Research Board Project HR-1. The Loess and Glacial Till Materials of Iowa; an Investigation of Their Physical and Chemical Properties and Techniques for Processing Them to Increase Their All-Weather Stability for Road Construction. The research, started in 1950, was done by the Iowa Engineering Experiment Station under its project 283-S. The project was supported by funds from the Iowa State Highway Commission.

Soil Stabilization with Lime, Iowa Highway Research Board Bulletin No. 25, 1961

This is the fifth publication in a series of compilations of the reports on research completed for the Iowa State Highway Commission. This research was done for the Iowa State Highway Research Board Project HR-1, "The Loess and Glacial Till Materials of Iowa; an Investigation of Their Physical and Chemical Properties and Techniques for Processing Them to Increase Their All-Weather Stability for Road Construction." The research, started in 1950, was done by the Iowa Engineering Experiment Station under its project 283-S. The project was supported by funds from the Iowa State Highway Commission. The principal objectives of the project may be summed up as follows: 1. To determine by means of both field and laboratory studies the areal and stratigraphic variation in the physical and chemical properties of the loess and glacial till materials of Iowa. 2. To develop new equipment and methods for evaluating physical and chemical properties of soil where needed. 3. To correlate fundamental soil properties with the performance of soils in the highway structure. 4. To develop a scientific approach to the problem of soil stabilization based on the relationships between the properties of the soils and those of the admixtures. 5. To determine the manner in which the loess and glacial till materials of Iowa can be processed for optimum performance as highway embankments, sub-grades, base courses, and surface courses.

Chemical Stabilization and Physicochemical Properties of Soils, HR-97, Special Report, 1966

This project was initiated to gain a better understanding of the phenomena which affect the engineering behavior of soils containing colloidal size particles and to find chemical methods of treatment which could improve the engineering performance of such soils.

Chemical Stabilization and Physicochemical Properties of Soils, HR-97, Final Report, 1966

This project was initiated to gain a better understanding of the phenomena which affect the engineering behavior of soils containing colloidal size particles and to find chemical methods of treatment which could improve the engineering performance of such soils.

Investigations into the mechanism of orotidine 5'-monophosphate decarboxylase: Sources of substrate destabilization and transition state stabilization

Orotidine 5′-monophosphate decarboxylase (OMPDC) achieves a rarely paralleled rate acceleration, yet the catalytic basis prompting this enhancement have yet to be fully elucidated. To accomplish decarboxylation, OMPDC must overcome the high energy barrier due to the localized anionic charge of the intermediate. Mechanistic studies employing enzyme mutagenesis and product or intermediate analogues were used to investigate possible transition state stabilization by a carbene resonance structure. Viability of the carbene structure depends upon a key hydrogen bond between O4 of the substrate and the amide backbone of a conserved serine or threonine. Substitution of the conserved residue with Pro resulted in a kcat/KM of 1 M-1s-1; deletion of the FUMP O4 resulted in a product analogue that does not undergo H6 exchange or inhibit decarboxylation. Hence, indirect evidence reveals the O4-backbone interaction plays an important role for binding and catalysis. OMPDC likely has honed multiple mechanisms to attain its remarkable catalysis. The successful crystallizations of OMPDC a decade ago sparked hypotheses that structure and sequence conserved residues induced productive strain on the substrate-enzyme complex. Here, we demonstrate a new source of stress: a hydrophobic pocket adjacent to the OMP carboxylate that exhibits kinetic parameters characteristic of substrate destabilization. Substitution of these residues with hydrophilic side-chains, by providing hydrogen-bonding partners, decreased kcat by 10 to 10^4–fold. The same substitutions display very little change in the rate of product H6 exchange, supporting that this hydrophobic pocket affects the substrate-enzyme complex before the transition state. We also provide evidence that hydrophilic residues can insert water molecules into the pocket with detrimental effects to catalysis.

Interaction-free measurements by quantum Zeno stabilization of ultracold atoms

Quantum mechanics predicts that our physical reality is influenced by events that can potentially happen but factually do not occur. Interaction-free measurements (IFMs) exploit this counterintuitive influence to detect the presence of an object without requiring any interaction with it. Here we propose and realize an IFM concept based on an unstable many-particle system. In our experiments, we employ an ultracold gas in an unstable spin configuration, which can undergo a rapid decay. The object-realized by a laser beam-prevents this decay because of the indirect quantum Zeno effect and thus, its presence can be detected without interacting with a single atom. Contrary to existing proposals, our IFM does not require single-particle sources and is only weakly affected by losses and decoherence. We demonstrate confidence levels of 90%, well beyond previous optical experiments.

Hydric behavior of earth materials and the effects of their stabilization with cement or lime: study on repair mortars for historical rammed earth structures

Earthen building materials bear interesting environmental advantages and are the most appropriate to conserve historical earth constructions. To improve mechanical properties, these materials are often stabilized with cement or lime, but the impact of the stabilizers on the water transport properties, which are also critical, has been very rarely evaluated. We have tested four earth-based repair mortars applied on three distinct and representative rammed earth surfaces. Three mortars are based on earth collected from rammed earth buildings in south of Portugal and the fourth mortar is based on a commercial clayish earth. The main objective of the work was over the commercial earth mortar, applied stabilized and not stabilized on the three rammed earth surfaces to repair, to assess the influence of the stabilizers. The other three earth mortars (not stabilized) were applied on each type of rammed earth, representing the repair only made with local materials. The four unstabilized earth materials depicted nonlinear dependence on t1/2 during capillary suction. This behaviour was probably due to clay swelling. Stabilization with any of the four tested binders enabled the linear dependence of t1/2 expected from Washburn's equation, probably because the swelling did not take place in this case. However, the stabilizers also increased significantly the capillary suction and the capillary porosity of the materials. This means that, in addition to increasing the carbon footprint, stabilizers like cement and lime have functional disadvantages that discourage its use in repair mortars for raw earth construction.

Development of nanostructured hydrogel for spatial and temporal controlled release of active compounds

L’utilisation de nanovecteurs pour la livraison contrôlée de principes actifs est un concept commun de nous jours. Les systèmes de livraison actuels présentent encore cependant des limites au niveau du taux de relargage des principes actifs ainsi que de la stabilité des transporteurs. Les systèmes composés à la fois de nanovecteurs (liposomes, microgels et nanogels) et d’hydrogels peuvent cependant permettre de résoudre ces problèmes. Dans cette étude, nous avons développé un système de livraison contrôlé se basant sur l’incorporation d’un nanovecteur dans une matrice hydrogel dans le but de combler les lacunes des systèmes se basant sur un vecteur uniquement. Une telle combinaison pourrait permettre un contrôle accru du relargage par stabilisation réciproque. Plus spécifiquement, nous avons développé un hydrogel structuré intégrant des liposomes, microgels et nanogels séparément chargés en principes actifs modèles potentiellement relargués de manière contrôlé. Ce contrôle a été obtenu par la modification de différents paramètres tels que la température ainsi que la composition et la concentration en nanovecteurs. Nous avons comparé la capacité de chargement et la cinétique de relargage de la sulforhodamine B et de la rhodamine 6G en utilisant des liposomes de DOPC et DPPC à différents ratios, des nanogels de chitosan/acide hyaluronique et des microgels de N-isopropylacrylamide (NIPAM) à différents ratios d’acide méthacrylique, incorporés dans un hydrogel modèle d’acrylamide. Les liposomes présentaient des capacités de chargement modérés avec un relargage prolongé sur plus de dix jours alors que les nanogels présentaient des capacités de chargement plus élevées mais une cinétique de relargage plus rapide avec un épuisement de la cargaison en deux jours. Comparativement, les microgels relarguaient complétement leur contenu en un jour. Malgré une cinétique de relargage plus rapide, les microgels ont démontré la possibilité de contrôler finement le chargement en principe actif. Ce contrôle peut être atteint par la modification des propriétés structurelles ou en changeant le milieu d’incubation, comme l’a montré la corrélation avec les isothermes de Langmuir. Chaque système développé a démontré un potentiel contrôle du taux de relargage, ce qui en fait des candidats pour des investigations futures.

Pharmacokinetic Profile of Liposome-Encapsulated Ropivacaine after Maxillary Infiltration Anaesthesia

The aim of this study was to determine the pharmacokinetic parameters of liposomal ropivacaine after dental anesthesia in 14 healthy volunteers. In this randomized, double-blind and crossover study, the volunteers received maxillary infiltration of liposome-encapsulated 0.5% ropivacaine and, 0.5% ropivacaine with 1:200,000 epinephrine in two different sessions. Blood samples were collected before and after (from 15 to 1440 min) the administration of either ropivacaine formulation. HPLC with UV detection was used to quantify plasma ropivacaine concentrations. The pharmacokinetic parameters AUC(0-24) (area under the plasma concentration x time curve from baseline to 24 h), AUC(0-infinity) (area under the plasma concentration-time curve from baseline to infinity), C-max (maximum drug concentration), CL (renal clearance), T-max (maximum drug concentration time), t(1/2) (elimination half-life) and Vd (volume of distribution) were analyzed using the Wilcoxon signed-rank test. No differences (p > 0.05) were observed between both formulations for any of the pharmacokinetic parameters evaluated and plasma ropivacaine concentrations, considering each period of time. Both formulations showed similar pharmacokinetic profiles, indicating that the liposomal formulation could be a safer option for use of this local anesthetic, due to the absence of a vasoconstrictor.

Manufacturing methods for liposome adjuvants

A wide range of studies have shown that liposomes can act as suitable adjuvants for a range of vaccine antigens. Properties such as their amphiphilic character and biphasic nature allow them to incorporate antigens within the lipid bilayer, on the surface, or encapsulated within the inner core. However, appropriate methods for the manufacture of liposomes are limited and this has resulted in issues with cost, supply, and wider scale application of these systems. Within this chapter we explore manufacturing processes that can be used for the production of liposomal adjuvants, and we outline new manufacturing methods can that offer fast, scalable, and cost-effective production of liposomal adjuvants.