Dissertations / Theses on the topic 'Matrices de délivrance de principes actifs'
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Loth, Capucine. "Exploring hydrogels based on the self-assembly of a Fmoc-based tripeptide : physicochemical characterization and antibacterial properties." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAE002.
Hydrogels are 3D networks of fibers that retain large amounts of water when swollen. Due to their biocompatibility, they are increasingly used for drug delivery. To develop antibacterial peptide-based hydrogels, this dissertation presents two studies based on the use of a fluorenylmethoxycarbonyl (Fmoc)-protected phosphorylated tripeptide that can self-assemble into a hydrogel. In the first study, different preparation conditions (pH, salt, presence of polysaccharide) were investigated to obtain a self-healing and antibacterial hydrogel capable of releasing an antibiotic, florfenicol. In the second study, a solid-phase peptide and phosphoramidite synthesis strategies were combined to add florfenicol to the Fmoc-protected tyrosine phosphate via a phosphodiester, which can be cleaved by nucleases produced by bacteria. Encouraging results showed the formation of the targeted compound, paving the way for the design of a self-defensive antibacterial peptide
Chabre, Yoann. "Matériaux dendritiques pour la délivrance de principes actifs." Nice, 2006. http://www.theses.fr/2006NICE4070.
This work deals with dendritic prodrugs synthesis and characterization for drug delivery towards biomedical therapeutics and ophthalmologic applications. Dendrimers are well-defined, discrete macromolecules with a high degree of molecular uniformity and monodispersity, which possess cavities and a strictly controlled number of functional groups on their periphery. Those features, combined with polymers advantages, multivalency, adhesive or molecular recognition effects make them attractive for the development of dendritic drug delivery systems. The first part of this work focussed on the selection and the optimization of specific structural elements in order to offer satisfactory compromise between structure-properties relationships (water solubility, biocompatibility and reduced toxicity, enzymatic degradability) and to synthesize new symmetric dendritic architectures bearing drugs in a covalent way for ophthalmology applications. The synthesis of non-symmetric structures was elaborated in a second part. Introduction of additional structural variables contributed to the molecular complexity enhancement in order to modulate in a more efficient way drug delivery processes and to their possible use in polytherapy. Preliminary studies concerning enzymatic degradation of our dendritic prodrugs are described in the last part of this work. In vitro studies highlighted “multiplicity effect” and the influence of several structural parameters modulating drug delivery processes
Ramadan, Alyaa Adel. "Etude de systèmes lipidiques de délivrance de principes actifs." Phd thesis, Université d'Angers, 2010. http://tel.archives-ouvertes.fr/tel-00586347.
Ramadan, Alyaa. "Etude de systèmes lipidiques de délivrance de principes actifs." Angers, 2010. http://www.theses.fr/2010ANGE0030.
This thesis highlighted the importance of lipid-based carriers and their pharmaceutical implications in the delivery of drugs of different nature for dermal and oral administration. The general introduction provided an overview of the types of lipid-based delivery systems with more emphasis on solid lipid nanoparticles ( SLN ) and lipid nanocapsules ( LNC ). In the first part, Clobetasol propionate ( CP )-loaded SLNs were prepared to improve the performance of long term topical corticosteroid therapy. Skin permeation ex-vivo data indicated that the skin retention of CP increased using the SLN test hydrogel formulation more than that a commercial gel. The second part focused on LNCs. Chapter 1 of this part aimed at encapsulating the hydrophilic macromolecule, fondaparinux ( F ), into LNCs by a novel patented two microemulsion ( ME ) strategy. This is based on the incorporation of a precarrier F-loaded ME into a second ME prepared using the phase inversion temperature plus temperature cycling methodology. LNCs formulated using Imwitor/Span were the best ( 59 nm and 48% incorporation efficiency). Chapter 2 aimed at enhancing the loading of anionic F by using cationic LNCs (~50 nm and 80-100% entrapment efficiency). In vivo study in rats administered F-loaded LNCs orally in comparison with a solution market product demonstrated that caionic LNCs significantly increased F bioavaibility and anti-factor Xa effect in a dose-dependent fashion. Data provided a proof of concept for the potential oral bioavailability of F. This offers great promise for a more convenient chronic anticoagulant therapy replcing the currently used injections
Louttani, Salma. "Boite moléculaire photostimulable pour la délivrance de principes actifs." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPASF088.
The work described in this thesis consists in the study of new vectors for active substances based on cyclodextrin (CD) nanotubes. The first part discussed about the choice of γ-CD as nanotube precursor, thanks to the results obtained by complexation of several active substances. After large scale synthesis of γ-CD nanotubes, the complexation conditions have been optimized and extended to nanotubes with different length and inter-CD bridges. A correlation between structure and the kinetics of active substance release has been carried out and allowed to refine the structure according to the has desired properties. For this purpose, the synthesis of a nanotube bearing photoswitchable extremities based on azobenzene moieties been investigated. After the synthesis optimization of a new heterodifunctional azobenzene derivative, the synthesis of a new polyrotaxane has been optimized to obtain a number of cyclic molecules and azobenzenes compatible with the structure of the desired nanotube. This compound has been successfully isolated and characterized such as new nanotube. A photochemical study evidenced the opening nanotube under UV stimuli, which lead to the use of the nanotube/curcumin complex in biology
Skandarani, Nadia. "Développement de nanocapsules lipidiques pour la délivrance de principes actifs." Thesis, Besançon, 2014. http://www.theses.fr/2014BESA2071/document.
The development of nanotechnology in the medical field has attracted considerable interest in recent years, including the use of nanoparticles for drug delivery. Nanoparticles offer unique opportunities for delivery of active drugs such as genes (gene therapy), anti-cancer (chemotherapy) or photosensitizers (photodynamic therapy, PDT). The major challenge, however, remains the delivery of therapeutic molecules to their site of action while keeping their integrity and their therapeutic effect.The research focus of this thesis is the use of lipid nanocapsules as a multifunctional platform for the delivery of drugs. One goal is the development of stable lipid nanocapsules, functionalized with polyethyleneimine and capable of effectively delivering a plasmid DNA and an anti-cancer (paclitaxel) as part of a combination therapy. The applications of these nanocarriers for transfection and delivery of chemotherapeutic were performed in vitro.Moreover, the ability of lipid nanocapsules to encapsulate photosensitizers for photodynamic therapy has been studied in vitro, and the results showed that the encapsulation of two molecules of PS in the nanocapsules allows a synergy photodynamic effect while protecting the PS from photo degradation.Finally, encapsulating an ion channel TRPM8 agonist (menthol) is the subject of the last chapter. The study by calcium imaging of the release of this lipophilic molecule in vitro confirmed the potential of lipid nanocapsules as nanocarriers of drugs
Castagnos, Pauline. "Vésicules catanioniques : design et mécanismes de délivrance de principes actifs." Toulouse 3, 2011. http://thesesups.ups-tlse.fr/1412/.
Sugar-derived catanionic surfactants self-assemble spontaneously into vesicles, which can encapsulate either hydrophilic drugs inside their aqueous core or hydrophobic and amphiphilic drugs inside their bilayer. Their biocompatibility, as well as their stability under time and dilution in biological media, allow to consider the use of these organized molecular systems for drug vectorization and delivery. In the present work, a mechanistic study showed these eco-designed and adjustable systems are able to fuse spontaneously with lipid assemblies mimicking cell membranes, provided that these latter present organization defects inside the bilayer. Cellular interaction mechanisms of such supramolecular systems were elucidated on cancer cell lines, by confocal microcopy and flow cytometry techniques. On the one hand, macropinocytosis, clathrin and caveolae pathways were shown to intervene as major active processes of cellular uptake of vesicles. The simultaneous intervention of these three pathways of endocytosis enables a progressive drug release through complementary mechanisms. On the other hand, experimental results verified that catanionic vesicles are capable of fusing with cell membranes. This spontaneous membrane fusion, concomitant with endocytosis, provides to these innovative systems the ability to deliver hydrophilic compounds directly inside cytoplasm. Numerous perspectives of such systems can thus be foreseen. An application towards vectorization of photosensible drugs was initiated in the present work, in order to fight cutaneous cancer through photodynamic therapy. These vectors, charged with hydrophobic active principles, showed enhanced stability and promising in vitro results for treatment of skin melanoma and oral squamous carcinoma
Racine, Lisa. "Elaboration de biomatériaux pour la délivrance contrôlée de principes actifs hydrophobes." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV061/document.
Due to their high biocompatibility, macroscale hydrogels have been studied as promising materials for the design of drug delivery systems (DDS). Such systems devoted to the local administration and prolonged drug release can improve the efficacy of pharmaceutical coumpounds while limiting undesired side-effects. Hydrogels present a high water content and soft consistency with mechanical properties that can match those of biological tissues. Nevertheless, these systems are essentially limited to the delivery of hydrophilic drugs. Our approach for extended release of hydrophobic drugs is to design composite materials composed of lipid nanoparticles (LNPs) entrapped within polysaccharide hydrogels. We selected two polysaccharides which are currently used in pharmaceutical and biomedical applications: carboxymethylcellulose (CMC) and chitosan (CS). We also used poly(ethylene glycol) (PEG) as a plasticizer to tune the matrix mechanical properties. Three types of LNP-loaded hybrid materials were studied; i) bulk CMC/PEG hydrogels, ii) CS/PEG films, and iii) CS/PEG sponges. These materials were chemically crosslinked through attractive click reactions. LNPs were successfully entrapped within the three materials without affecting their properties. A deeper study was conducted with the CMC/PEG composite hydrogel. The LNP release profiles were correlated with the network structure and particles properties. The different materials appear promising systems for the time-controlled delivery of therapeutics
Delorme, Victor. "Nouveaux systèmes copolymères amphiphiles biodégradables pour la délivrance de principes actifs anticancéreux." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTS140.
This work presents the synthesis of biocompatible and biodegradable amphiphilic copolymers for the formation of anticancer drug delivery systems. These copolymers consist of a poly-(ε-caprolactone) (PCL) chain, a biocompatible and biodegradable hydrophobic polyester, on which hydrophilic oligomers of dextrane or chitosane are grafted. These new copolymer structures are called “reverse” structures, the “classic” ones being made of a polysaccharide chain with PCL grafts. The PCL chain was propargylated via an anionic method developed by our team, while azide functions were grafted on oligosaccharides at a chain end of dextrane, but along the chain in chitosan, thanks to its amine functions. Copolymers were obtained by CuAAC click coupling between the activated PCL and oligosaccharides. In the case of chitosan, the amines of the chain allowed the coupling of mannose squarate, a cancer cell targeting agent, as well as a functionalization in the form of thiols which allow coupling by thiol-yne reaction on propargylated PCL. These copolymers form nano objects in aqueous media which, in the case of the PCL-g-dextrane structure, are forming micelles that encapsulate doxorubicin, which is further released in a pH- dependent way. Biological studies have shown that these charged micelles are toxic to cancer cells and not to healthy cells and are preferentially internalized by cancer cells. These results demonstrate a high degree of selectivity of action against tumor cells
Philippe, Isabelle. "Liberation controlee de principes actifs a partir de matrices hydrophiles." Strasbourg 1, 1990. http://www.theses.fr/1990STR15031.
Cheibani, Ismail. "Formation et clivage de gels de nanoparticules lipidiques : systèmes de délivrance de principes actifs." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV017/document.
Nanotechnology became for several years a major development in the areas of diagnostics, imaging, drug delivery, therapeutic monitoring, and tissue engineering. The administration of non-injectable products in their free form or with high toxicity, can be facilitated by the use of nanocarriers, changing their distribution. They therefore reduce the doses administered, limit side effects and direct the contents of the vector (contrast agent, drug) to a target organ or tumor, by presenting to the surface thereof targeting molecules of these areas specific.This thesis fits into this theme : we have explored the possibilities of forming chemical gels based on lipid nanoparticles which are composed of an oily heart can encapsulate small hydrophobic molecules and a layer of surfactants allowing stabilization of the droplets in the aqueous phase.We have synthesized several PEGylated functionalized surfactants (thiol, maleimide, amine, and oxyamines ONB-maleimide). synthesis protocols of these surfactants are refined and repeatable.These surfactants were incorporated into the surface of lipid nanoparticles. The functionalized nanoparticles thus obtained have been characterized and the functions present at their surface are highlighted.Different kinds of chemical gels stable, resistant to dilution, fast and controllable manufacturing have been developed.These chemical gels can be used in the future for encapsulating proteins or drugs
Klausen, Maxime. "Nouvelles sondes moléculaires photo-activées pour la délivrance de principes actifs : de la conception aux applications biologiques." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0077.
Photolabile protecting groups (PPGs) have attracted growing interests in many fields of chemistry and biology. Light-induced release of biological agents, commonly known as “uncaging”, has thus emerged as an interesting process for drug delivery or investigation of biological phenomena. Combining this tool with the intrinsic advantages of two-photon (2P) excitation (2PE) in the NIR is however a challenge. In this work, we use different engineering routes towards new efficient 2P uncagers.First we demonstrate that combining quadrupolar 2P light harvesting antennas with suitable uncaging subunits leads to efficient release of active molecules upon 2PE. In these FRET-based systems, gradual adjustments of the constitutive building blocks allowed us to tune key parameters such as photophysical properties, FRET efficiency, and kinetics of photorelease. In particular, coumarin-based tandem systems, in which absorption and emission of the donor-acceptor pair best match, eventually led to record δu values for uncaging of carboxylic acids.We then assessed the critical water-solubility issue by introducing hydrophilic units onto our cooperative PPGs. New hydrophilic and amphiphilic systems, suited for controlled release of neurotransmitters or anti-cancer agents, were designed from our multi-chromophoric systems.Finally, in our effort towards better understanding of the structure-properties relationships in coumarin PPGs, we synthesized a small library of π-extended DEAC cages bearing strong electron-withdrawing moieties, and assessed their efficacy for 2P uncaging of glycine. With this study, a step was made towards rationalization of the uncaging quantum yield in coumarin cages
Soussan, Elodie. "Conception de vésicules catanioniques dérivées de sucre et étude de leur mécanisme de délivrance de principes actifs." Toulouse 3, 2007. http://thesesups.ups-tlse.fr/14/.
The present work focused on the development of new sugar-based catanionic systems able to spontaneously form vesicles in water in order to deliver drugs towards cells. To validate these systems for drug delivery, original investigation methods based on the physical properties of giant magnetoliposomes and the electric properties of cell membranes have proven that a membrane fusion phenomenon is implicated between catanionic vectors and cells. This mechanism of fusion allows vectorization of hydrophilic drugs, encapsulated inside vesicle aqueous compartment, directly towards cell cytoplasm. After fusion, the internalisation of a vesicle bilayer fraction unables the delivery of lipophilic molecules confined inside the vesicle membrane. Catanionic vesicles are thus a versatile system able to deliver drugs within cells whatever their hydrophilicities. This new vector system offers promising application in vectorisation
Rippe, Marlène. "Systèmes transporteurs de principes actifs hydrophobes à base de glycoaminoglycanes thermosensibles : vers une plateforme polyvalente de délivrance." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV004/document.
In the field of drug delivery systems, polymeric nanogels obtained by the self-assembly of biocompatible amphiphilic polymers in water have emerged as one of the most promising nanocarriers for various hydrophobic drugs. These systems offer several advantages such as enhanced hydrophobic drug solubility in water, decreased side effects, and improved drug delivery to tumor tissues via the enhanced permeability and retention (EPR) effect. In this regard, stimuli-responsive polymeric nanogels are attractive platforms for drug delivery due to their ability to change their physical and/or chemical properties in response to an external stimulus such as light, magnetic field, pH or temperature. Thermoresponsive polymers are particularly interesting due to their ability to undergo a reversible thermally-induced phase transition without the need of additional reagents. In this context, our aim was to engineer and to study a new class of thermoresponsive, biocompatible and biodegradable nanogels based on glycoaminoglycans (GAGs) through the modification of the polysaccharide backbone with a thermoresponsive copolymer of di(ethylene glycol) methacrylate (DEGMA) and n-butylmethacrylate (BMA)). The latter was properly designed to obtain stable nanogels at room temperature. The versatile synthetic route to nanogels also allowed their further shell-crosslinking to capture the nanogel structure at low temperature. The choice of the GAGs forming the hydrophilic shell can be exploited to control their biological behavior. In order to use these systems as a versatile platform for delivery of active ingredients and other molecules of interest, we investigated the possibility of incorporating iron oxide nanoparticles for magnetic guidance, imaging and hyperthermia treatment. The syntheses of the magnetic component as well as the design of the nanocarrier are key steps to achieve a magnetically-responsive nanodelivery system capable of efficient targeting
Beesh, Mustafa. "Mise au point de nouvelles formulations pharmaceutiques orales à délivrance ciblée de principes actifs au niveau du côlon." Strasbourg, 2010. https://publication-theses.unistra.fr/public/theses_doctorat/2010/BEESH_Mustafa_2010.pdf.
The work described in this manuscript deals with the synthesis, the enzymatic degradation and the physicalchemistry characterization of new excipients based on a natural polysaccharide, dextran. These excipients can serve coating or agent matrix for the realization of oral pharmaceutical forms at colon-specifie release of the active ingredients. To this end, two main strategies for syntheses were performed on dextran to make it hydrophobie. The first is based on the esterification of hydroxyl groups of dextran to prepare three families of dextran esters (acetate, propionate and butyrate) with three Degree of substitution (1 , 2 and 3). The second strategy allows to obtain three types of dextran block copolymers (di, tri and tetra-block copolymers) by freeradical emulsion polymerization of one or more acrylic monomers (MA, MMA and MAA) on the block of dextrans. The beneficial results of in vitro release of theophyllin from tablets coated individually with different types of dextran block copolymers were allowed to determine the potential uses of dextran block copolymers to deliver oral dosage forms in the colon
Dubois, Victor. "Nouveaux outils moléculaires photo-activables pour la délivrance contrôlée de principes actifs : De la conception aux applications biologiques." Thesis, Bordeaux, 2021. http://www.theses.fr/2021BORD0029.
Photosensitive protecting groups (PPGs) are small organic chromophores able to release bioactive compounds thanks to light irradiation. Such molecular tools have attracted a growing interest in the field of biology for applications such as therapy or physiology. However, while most PPGs possess satisfying photochemical properties for 1-photon excitation, designing efficient PPGs for 2-photon excitation (2PE) in the NIR region is still very challenging. In this work, we decided to use two different approaches towards new efficient PPGs for two-photon (2P) induced photorelease.First, we decided to investigate the direct modification of the molecular structure of coumarinyl PPGs in order to enhance their 2P absorption (2PA) ability. In this context, the synthesis of PPGs with modified - conjugated and push-pull systems combined with the introduction of molecular symmetry led to a set of very efficient PPGs for 2PE. In addition, a small library of dipolar PPGs bearing electron withdrawing groups allowed us to make a step towards the rationalization of the uncaging quantum yield. One of our new compounds is currently being submitted to neurophysiological experiments to validate our strategy.The second part of this work concerns the conception of energy transfer (FRET or PET) based tandem systems between a strong 2P absorber antennae and appropriate PPG. Again, the photophysical and photochemical studies of our new compounds showed very high 2P photosensitivity. While these last results contributed to validate our strategy, some of the disappointing results obtained also contributed to point out the key parameters required in the elaboration of such architectures
Vijayarangan, Vinodini. "Application des plasmas froids à la pénétration de principes actifs dans la peau." Electronic Thesis or Diss., Orléans, 2021. http://www.theses.fr/2021ORLE3207.
This thesis was performed under a CIFRE contract within LVMH Research, in collaboration with two academic laboratories : GREMI (University of Orléans / CNRS) and CBM (CNRS). The aim of the project was to assess the use of a cold atmospheric pressure plasma jet for the cutaneous penetration of molecules of cosmetic interest. This thesis was carried out along three major axes. In the first, the work consisted in identifying and evaluating the characteristics of a plasma jet in front of a skin explant. A study was carried out to observe the behavior of a helium flow during plasma treatments with various characteristics by Schlieren imaging, to identify the type of excited species produced by spectroscopy, to measure the electric field associated with the plasma jet and its temperature in the environment of the explant. The second axis of the study was focused on the disturbances induced on the skin explant. The impact of plasma treatment on the skin barrier was assessed through measurements of transepidermal water loss, pH, wettability and skin lipid degradation. The structural integrity of collagen was visualized by AFM and that of the epidermal and dermal layers by immunostaining. Finally, in thethird axis, the work focused on skin penetration after plasma treatment using fluorescent molecules as well asactive ingredients of cosmetic interest such as caffeine and hyaluronic acid. The effective penetration of these molecules through the skin was evaluated, measured and quantified using Franz cells with quantification byabsorbance measurements, by HPLC and by fluorescence or MALDI FTICR imaging on sections obtained. from treated explants. The studies carried out along these three axes have thus made it possible to highlight the key parameters allowing effective skin penetration without damage to the skin by cold plasma treatment
Ciancone, Mathieu. "Complexes de métal-bis(dithiolène) pour la théranostique du cancer : thérapie photothermique, délivrance photocontrôlée de principes actifs et propriétés photoacoustiques." Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1S090.
This work focuses on the exploitation of the photothermal properties in the near-infrared (NIR) region of neutral metal-bis(dithiolene) complexes for biomedical applications. Encapsulation of these complexes in polymer nanoparticles or in thermosensitive liposomes allowed to use theirremarkable photothermal effect for cancer theranostics. This work demonstrates that theformulated photoactive nanovectors have great potential to be used as photosensitizers forphotothermal therapy. Moreover, laser irradiation of the encapsulated complex allowed to finely tune the permeability of the cargo, thus leading to the release of the co-encapsulated agent with a high spatiotemporal control. This work also demonstrates that the photothermal effect of metal-bis(dithiolene) complexes can be used for designing the design of contrast agents for photoacoustic imaging. Finally, this work focused on the study and the comparison of the phtotothermal properties of seven molecular agents. The results of this study clearly show that the remarkables properties of metal-bis(dithiolene) complexes, coupled with their excellent photochemical and thermal stability, make them very promising candidates for cancer theranostics
Peers, Soline. "Elaboration de bio-systèmes à relargage retardé de principes actifs : hydrogels physiques de chitosane fonctionnalisés par des liposomes." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSEI010.
This work deals with the development of an original biomaterial in view of its application as drug delayed-release device in biomedical area. To overcome classic issues that may be encountered with common drug delivery systems such as the “burst effect” or fast outside diffusion of drugs, a « hybrid » system composed of liposomes entrapped within a chitosan physical hydrogel was developed. Its elaboration process consists in the addition of a suspension of pre-formed phosphatidylcholine liposomes within a chitosan solution before gelation process. A characterization of different components of the system and an optimization of the elaboration process were achieved. The release properties were firstly investigated using a water-soluble fluorescent model molecule, carboxyfluorescein (CF). The concept of delayed-release was confirmed. Indeed, the release of CF, assayed by fluorescence spectroscopy, was found to be higher in the “drug-in-hydrogel” systems in comparison with the “drug-in-liposomes-in-hydrogels” ones. Based on these results, the release of two drugs, rifampicin (RIF), a broad spectrum antibiotic, and lidocaine (LID), a local anaesthetic and anti-arrhythmic drug, were also studied. This work corroborated the data obtained for the model molecule, that is to say a significant delayed release for « hybrid » systems in comparison to hydrogels without liposome. Various characterizations were carried out to examine rheological properties and morphologies of assemblies. These first results showed that such systems could be a step forward in drug delivery, and highlighted the use of liposomes as drug « reservoirs » within assemblies
Klak, Marie-Cécile. "Délivrance moléculaire par contrôle de la dynamique de gels supports : étude en vue de l'élaboration d'un nouveau type de pansement." Thesis, Cergy-Pontoise, 2011. http://www.theses.fr/2011CERG0508.
Gels are soft matter composed of a liquid phase entrapped in a polymer network. Biopolymers can form gels, and then called biogels. Biocompatible, bioresorbable, these structures are really closed to extracellular matrix. Furthermore, aqueous phase represents 95% of the whole gel. Its possible to include molecules inside this liquid phase. Molecules are then released from the gel to the external environment.During this PhD project, we have studied the molecular release from different gelatin matrices.First, the release of a large range of molecules from chemical gelatin gel was studied. Different molecular weights and ionic charges were compared. The results show that the release depend on both the network structure and the include molecule characteristics. Moreover, the simultaneous release of two different compounds is possible.In the second part of the manuscript, gelatin gel was modified in order to control or stimulate the release. Five matrices were synthesised and tested. At first, alginate, a viscous polymer was introduced into the aqueous phase. Alginate is able to limit diffusion and its hydrolysis stimulates molecular release. Then, the gelatin network itself was modified. The synthesis of a second network within gelatin gel increases the entrapment of molecules. On the contrary, the use of ephemeral gels, where gelatin network hydrolysis is programmed and timed-controlled, leads to stimulate the molecular release.Then, a simple model elaborated from Fick's second law was constructed to describe these different delivery systems. The originality of the model resides in the consideration of the steric hindrance inside the gel. This unique model is able to predict correctly the release kinetics of small and large molecules, with or without interaction with the solid network, the concomitant release of two molecules and the release from ephemeral gels.Finally, all results were used in order to develop a new wound dressing able to deliver drugs and stimulate chronics wound healing
Yang, Liu. "Etude des micelles biorésorbables formées par auto-assemblage des copolymères à blocks polylactide/poly(éthylène glycol) pour la délivrance contrôlée de principes actifs." Thesis, Montpellier 1, 2010. http://www.theses.fr/2010MON13524.
A series of polylactide-poly(ethylene glycol) (PLA-PEG) block copolymers were synthesized by ring-opening polymerization of L- or D-lactide in the presence of mono- or dihydroxyl PEG. The molar mass, composition, crystallization and thermal properties were characterized by using DSC, NMR, GPC, etc. Bioresorbable micelles were obtained by direct dissolution method without using any organic solvents. Surface tension measurements were used to determine the critical micellar concentration of the copolymers. The results show that L/D mixed micelles are more stable than single ones due to strong stereocomplexation effect between L-PLA and D-PLA blocks. The aggregation behavior of micelles in aqueous medium was investigated in detail. It appears that mixed micelles present lower aggregation number than single ones. The hydrolytic degradation of the micelles was investigated under in vitro conditions. Paclitaxel was used as a model drug to investigate the in vitro and in vivo behavior of micelles as drug delivery system. The direct dissolution method yields comparable drug encapsulation efficiency and loading content as the traditional dialysis method. The drug encapsulation ability is higher for L/D mixed copolymer micelles than single micelles due to stereocomplexation. In vivo experiments show that paclitaxel is widely distributed and kept at high concentration levels in various tissues after administration of drug-loaded micelles. Compared with the current clinical formulation and micelles by dialysis, paclitaxel-loaded micelles by direct dissolution exhibit the highest antitumor ability
Coumes, Fanny. "Synthèse et caractérisation de copolymères amphiphiles à base de poly(acide lactique) et de poly(éthylène glycol) pour la délivrance de principes actifs." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON13522/document.
The objective of this work was to synthesize and characterize amphiphilic copolymers based on poly(ethylene glycol) (PEG) and poly(lactic acid) (PLA) intended for drug delivery applications. The polymers were chosen regarding to their biocompatibility and bioresorbability. Different architectures of amphiphilic copolymers were prepared, and their behavior in aqueous media, as well as their abilities to encapsulate drugs were studied. First, a graft copolymer was synthesized through copolymerization of a functional monomer, monopropargylated glycolide, with L-lactide to yield a functionalized polyester backbone. The latter was then grafted with different densities of hydrophilic branches of PEG. Then, a brush-like triblock copolymer was synthesized through ROP and ATRP. To this end, chain ends of a telechelic block of PLA were modified to yield a macroinitiator able to initiate oligo(ethylene glycol) methacrylate polymerization with variable substitution degrees. Self-assembly and drug loading studies revealed that architecture and hydrophobic/hydrophilic balance played a major role on the nature of the formed objects and on their encapsulation potential. Finally, to modulate and increase the efficacy of encapsulated drugs, functionalization strategies were realized. This is illustrated by the linking of a fluorescent model molecule on a triblock brush-like copolymer and, in a collaboration project, the linking of an immunostimulant peptide on an amphiphilic diblock system. Comparison with other formulations revealed that the conjugate allowed modulating and reinforcing the drug's efficacy
Jing, Jing. "Conception et évaluation de systèmes transporteurs de principes actifs hydrophobes à base de polysaccharides modifiés : vers de nouvelles approches pour la thérapie anti-cancéreuse." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00949208.
Nguyen, Régis. "De l'utilisation de biomolécules comme matrices pour favoriser la formation de molécules complémentaires." Palaiseau, Ecole polytechnique, 2002. http://www.theses.fr/2002EPXX0004.
Jean, Baptiste Elixène. "Amélioration des propriétés antibactériennes et anticoagulantes des prothèses vasculaires en polyester par immobilisation et libération contrôlée de principes actifs." Thesis, Lille 2, 2012. http://www.theses.fr/2012LIL2S043/document.
Synthetic vascular prosthesis likewise vascular endoprosthesis are prone to several complications after implantation into the human body. Infections, thromboses and late occlusions are the most challenging and the most common, leading to serious clinical consequences that are sometimes lethal. Management of those complications is still fraught with tremendous difficulties justifying the economic burden and the continuous efforts in research development for improving vascular prosthetic materials. This research investment is, however, yet to yield any great clinical advance. Previous studies conducted in our research laboratory have led to the development of polyester vascular prostheses coated with a polymer of hydroxypropyl-β-cyclodextrin. This was achieved in order to increase the loading and eluting capacities of these vascular prostheses towards several antibiotics. In the current works, we sought to determine the optimal conditions for effective controlled release of three antibiotics from those prosthetic platforms. We have also evaluated their efficacy in both in vitro and in vivo models of vascular infections. This was carried-out against nine different bacteria strains that are among the most common in human vascular infections. Moreover, we have assessed in vivo their safety, their healing properties, their systemic toxicity and their biocompatibility in the prospect of clinical application.The above-mentioned drug delivery system has been proved to be effective in releasing in situ the selected antibacterial agents over a seven-day desorption period in human plasma. Optimal batch concentration and time for prosthetic immersion into the antibiotic solutions were well compatible with current surgical practice standards. A bactericidal activity evidenced by significant reduction of bacterial adhesion, growth and proliferation was revealed when compared to appropriate controls in the various tested vascular infection models. We have also studied antibacterial molecules alone or in combination. In this latter setting, no antagonistic effects were depicted. This provides a unique opportunity to customize local antibiotic treatment delivered in situ from vascular device fabrics and to adapt it to the evolving ecology of both monomicrobial and polymicrobial vascular prosthetic infection. The polyester vascular prostheses coated with a polymer of hydroxypropyl-β-cyclodextrin were proved in vivo safe and demonstrated excellent biocompatibility, healing properties and tissue integration without any signs of systemic toxicity. [...]
Lemaire, Gaelle. "Elaboration de Nanoparticules hybrides et multiphasées innovantes pour la délivrance de principe actif." Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0054.
The limitations of commercial nanovectors or currently under development have motivated the development of new hybrid and core shell mesoporous silica nanoparticles (MSNP) for the control of molecular delivery.Therefore, new MSNP were designed for intracellular penetration (diameter between 30 and 60 nm, pore size of 2.8 nm). In order to make them hemocompatible and to control the kinetics of delivery of encapsulated active ingredients, these MSNP were coated with a lipid bilayer (MSNP+@SLB-). The lipid composition is inspired by the asymmetric membranes of the red blood cells.Since the MSNP+@SLB- technology has shown some limitations associated to the release of payloads which can be too fast (in the case of calcein) or to slow (case of rhodamine B), two major improvements have been made:1- The coating of SLB by an alginate nanogel, allowing an excellent control of the release of active molecules.2- Insertion of magnetic nanoparticles in the MSNP core, triggering the release of the active ingredient by hyperthermia.These new nanovector architectures enable the fine tuning of active ingredient delivery kinetics, reinforcing and expanding the applications of silicated vectors in the fields of biomedicine (oral and intravenous) and dermato-cosmetics (topical)
Ingani, Hyacinthe. "Etude des paramètres de formulation influençant les caractéristiques de libération de principes actifs à partir de matrices hydrophiles à base de gomme xanthane et conception de comprimés matriciels bicouches flottants." Doctoral thesis, Universite Libre de Bruxelles, 1987. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/213411.
Yessaad, Mouloud. "Développement d’outils prédictifs de la teneur en composés sensibles à l’oxydation au cours de la conservation dans les matrices nutritionnelles." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAC080.
When stored, the active ingredients (drugs, nutrients) may be subject to degradation that may change their original properties and make them unavailable. In addition, manufacturers and hospital pharmacists carrying out pharmaceutical preparations and / or dietary supplements have the need to carry out stability studies. These studies are long and costly because they must consider all the environmental parameters likely to influence the stability of the active principle, the matrix and the packaging. The aim of this thesis is to develop a tool that allows to estimate the degradation rates of vitamins and to project on the life span of nutritional active principles based on the use of computational models integrating at the same time product characteristics, matrix and storage conditions. The project took place in several phases targeting the water-soluble vitamins. First, a development and validation of a chromatographic assay method that quantifies all vitamins in a single analysis without interference with any degradation products. A study of the influence of the most important parameters was carried out with a design of experiments. The kinetics of degradation have been studied and modeled in several approaches. From the most appropriate model, a first simulation level was designed to determine the relevant influencing factors in the degradation of vitamins in terms of exploitable data. The deliverable, the calculator, should thus help guide industrial and hospital users in the choice of accelerated aging study conditions