Nanoparticles have received special attention over past few years as potential drug carriers for proteins/peptides and genes. Biodegradable polymeric poly (lactic-co-glycolic acid) (PLGA) nanoparticles are being employed as non-viral gene delivery systems for DNA. This work demonstrates a scalable technology for synthesis of nanoparticles capable of gene delivery. Cationic PLGA nanoparticles are produced by emulsiondiffusion- evaporation technique employing polyvinyl alcohol (PVA) as stabilizer and chitosan chloride for surface modification. A sonicator is used for the emulsion step and a static mixer is used for dilution in the diffusion step of the synthesis. A static mixer is considered ideal for the synthesis of PLGA nanoparticles as it is easily scalable to industrial production. The resulting nanoparticles are spherical in shape with size in the range of 100–250 nm and posses a zeta potential above +30 mV, indicating good stability of the colloid with a positive charge to bind to anionic DNA. The mechanism of nanoparticle formation was analyzed using multimodal size distributions (MSD), zeta potential data, and transmission electron microscopy (TEM) images. Several emulsion techniques and dilution effect were analyzed in this work. PVA acts as a compatibilizer for chitosan chloride and dilution of primary emulsion has little effect over the particle size of the PLGA nanoparticles.

L’objet de ce travail est la description de la dynamique de diffusion dans les polymères à l’approche de la transition vitreuse et notamment les processus de relaxation hors équilibre. Nous développons, pour les mélanges compressibles de polymères et polymère-solvant, un modèle thermodynamique qui permet de calculer les forces thermodynamiques dans des situations hors d’équilibre (formalisme général d’Onsager). La dynamique correspondante repose sur l’existence d’hétérogénéités dynamiques près de Tg dues aux fluctuations de concentration (modèle de Long et Lequeux). Nous avons développé deux méthodes. La première est basée sur une équation de Fokker-Planck décrivant, à l’échelle des hétérogénéités (quelques nm), la distribution des fluctuations de concentration de polymère et de solvant. Après l’étude des mécanismes de relaxation à cette échelle, nous étudions l’échelle macroscopique, pour rendre compte de la pénétration du solvant dans un matériau vitreux ou du séchage d’un mélange polymère-solvant près de Tg. La deuxième méthode consiste en la simulation de ces mécanismes de relaxation par une description spatiale. Celle-ci est basée sur une discrétisation de l’espace, chaque site pouvant échanger du solvant ou des monomères selon une dynamique décrite par des équations de Langevin non-linéaires couplées. Cette dernière méthode est plus générale mais plus coûteuse en temps de calculs. Nous montrons que les résultats obtenus des deux façons sont cohérents. Il s’agit de la première méthode permettant de décrire microscopiquement et quantitativement la diffusion de solvant près et en dessous de la transition vitreuse / The aim of this work is to describe the diffusion dynamics in polymers close to the glass transition (relaxation processes at non equilibrium states). A thermodynamic model for polymer-polymer and polymer-solvent blends is developed. It is able to compute the thermodynamic forces existing at non equilibrium for the mentioned blends (Onsagers formalism). The correspondent dynamic are based upon the existence of thermodynamic heterogeneities close to Tg due to concentration's fluctuations (Long-Lequeux model). Two methods were developed. The first is based on a Fokker-Planck equation which describes, at the heterogeneity scale (i.e. nanometric scale), the distribution of fluctuations of polymer and solvent. Following the study on the relaxation mechanism in the nanometric scale, a microscopic scale was then considered, in order to take in account either the solvent penetration within a glassy material or the drying of a polymer-solvent blend close to Tg. The second method consists in the simulation of the mentionned relaxation mechanisms using a spatial approach. This approach is based on a special discretization, each site being able to exchange solvent molecules or monomers according to the dynamics described by coupled non-linear Langevin equations. This second method is a more general approach. However the calculations related to it are more time-consuming. The results obtained by both methods are in good agreement. This is the very first method able to describe microscopically and quantitatively the solvents diffusion close to or below Tg

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