Táto práca sa zaoberá zvlákňovaním biopolymérov z taveniny. V teoretickej časti sú zhrnuté doterajšie poznatky o zvlákňovaní poly(3-hydroxy butyrátu) (PHB) a poly(mliečnej kyseliny) (PLA). Následne boli zvláknené polymérne zmesi na báze PHB s rôznym zložením, čo umožnilo štúdium vplyvu PLA, zmäkčovadiel a ich množstva na vlastnosti pripravených vlákien. Boli použité tri komerčné zmäkčovadlá (ATBC, PEG, A6) a dva experimentálne syntetizované. Zvláknenie bolo prevedené na troch rôznych zvlákňovacích linkách. Konvenčné zvlákňovacie linky s odťahovými rýchlosťami nad 150 m/min sa preukázali ako nevhodné pre spracovanie našich zmesí. Kvôli nedostatočnej pevnosti taveniny sú potrebné nízke odťahové rýchlosti. Boli pripravené vlákna s dĺžiacim pomerom 6,4; ktoré boli následne analyzované pomocou GPC, MDSC a ťahovej skúšky. Na základe nameraných teplôt skelného prechodu zmäkčovadlá ATBC a PEG vykázali lepšiu schopnosť zmäkčiť skúmané PLA/PHB zmesi. Vlákna obsahujúce A6 vykazovali najvyššiu pevnosť v ťahu (250 MPa) a modul pružnosti (2,7 GPa). Nakoniec bol skúmaný vplyv starnutia, tepla a vriacej vody na mechanické vlastnosti týchto vlákien.

Teoretická část této diplomové práce popisuje vlastnosti a možnosti modifikace poly(3-hydroxybutyrátu) (PHB) a amorfní poly(mléčné kyseliny) (PLA) a jejich směsí. V experimentální části je studována reaktivita Joncrylu, Raschigu a fosfitových činidel trifenylfosfitu, tris(nonylfenyl) fosfitu a difenylisodecylfosfitu s čistým PLA a PHB. Raschig, oligomerní aditivum na bázi polykarbodiimidu, prokázal v množství 2hm. % zvýšení viskozity taveniny obou polymerů, a proto byl použit k přípravě směsí o pěti hmotnostních poměrech PHB/(PHB+PLA). Vzorky s Raschigem a odpovídajícími nereaktivními vzorky byly studovány pomocí reologie, gelové permeační chromatografie a modulované diferenční kompenzační kalorimetrie. Výsledky naznačily reakce Raschigu v PHB/PLA směsích vedoucí k rozvětveným strukturám. Rychlost reakce však není nedostatečná ke kompenzaci poklesu viskozity v důsledku degradace při zpracování. Následně zůstává nezreagované množství Raschigu v matrici. Na základě těchto zjištění se dospělo k závěru, že Raschig se chová spíše jako relativně účinný stabilizátor reologických vlastností, než jako činidlo pro záměrnou modifikaci struktury směsí PHB/PLA. Za účelem studia mechanických vlastností těchto směsí byly ve dvoušnekovém extrudéru připraveny vzorky plastifikovány acetyltributylcitrátem.

No description available.

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Le poly (acide lactique) (PLA), est un polymère synthétisé à partir de ressources renouvelables, qui est l'objet de beaucoup d'études à l'heure actuelle mais qui souffre d'une faible résistance au choc. Le but de ce travail est de rechercher des pistes permettant la préparation d'un matériau à base de PLA avec une résistance au choc améliorée tout en minimisant la perte de résistance à la traction. Les travaux présentés ici ont étudié le rôle de nanoparticules élastomères de poly (acrylate de butyle) (PBA) chargées de laponite (LRD) (PBA-LRD) ainsi que de nanocomposites coeur-écorce (PBA-LRD)/poly(méthacrylate de méthyle) (PMMA) en tant qu'agents de renforcement d'une matrice de PLA. Ces nanoparticules ont été dispersées dans la matrice PLA à l'état fondu. La synthèse de ces nanoparticules a été effectuée par polymérisation en émulsion ou miniémulsion. La laponite a été incorporée dans les nanoparticules afin de minimiser la perte de la rigidité tout en améliorant la résistance au choc de PLA. Trois types de tensioactifs et des modifications de surface de la laponite ont été testées pour améliorer l'adhérence entre les particules de PBA et la matrice de PLA. Enfin une écorce de PMMA a été utilisée pour assurer la bonne adhérence entre les particules de PBA et de matrice PLA. Nous avons montré que les particules coeur-écorce ont permis d'augmenter la résistance au choc au 3 fois du PLA tout en réduisant la diminution du module d'Young et la perte de résistance à la traction (~25%). Les propriétés de les particules synthétiques et les propriétés des mélange du PLA avec les particules PBA ou particules coeur-écorce ont été étudiées par diverses techniques de caractérisation (DLS, FTIR, ATG, MET, MEB, RMN 1H, DSC, DMTA...) / Poly (lactic acid) (PLA), come from renewable resources, one of the most important biopolymers, suffers from weak impact resistance. The aim of this work is to develop a process that will allow preparing a PLA with improved impact resistance while minimizing loss in tensile strength. The work presented here examined in detail the synthesis of poly(butyl acrylate) (PBA) nanoparticles charged with laponite (LRD) (PBA-LRD) and (PBA-LRD) / poly(methyl methacrylate) (PMMA) core-shell nanocomposites. They were dispersed phase in PLA matrix and were synthesized by emulsion or miniemulsion polymerization. The clay such as laponite was included in these nanoparticles to minimize the loss of rigidity while improving the impact resistance of PLA. Note that three types of surfactants and some modify agents for LRD have been tried to improve the adhesion between the PBA particles and matrix PLA, PMMA was finally used to ensure a good adhesion between the PBA particles and the matrix. To this end, we explored successively the PLA blend, using PBA nanocomposites and the PBA/PMMA core-shell nanoparticles as reinforcing agents, with improved impact resistance, showing that core-shell particles allowed increasing of 3 times of impact strength of the PLA with a minimum amount of loss (~25%) in Young?s modulus and tensile strength. The properties of the synthetic particles and the properties of PLA blends have been demonstrated by various characterization techniques (DLS, FTIR, TGA, TEM, SEM, 1H-NMR, DSC, DMTA ...)

La conception de nanoparticules (NPs) polymériques pour le transport de médicaments dans la peau repose sur la compréhension du rôle de leurs compositions chimiques sur leurs interactions avec la peau, notamment la peau pathologique. Ce travail s'est attaché à définir le rôle de la composante hydrophile des NPs sur l'administration cutanée d'un principe actif lipophile modèle (cholécalciférol). Il a été remarqué que la composition hydrophile de polymères amphiphiles à base de PLA conditionnait les propriétés physicochimiques des NPs, notamment la taille, la surface, et la structure, tout comme la protection du cholécalciférol. Concernant l'absorption cutanée sur peau intacte, la composante hydrophile de NPs de 100 nm a eu peu d'influence. Une absorption cutanée du cholécalciférol légèrement plus importante a toutefois été obtenue à partir des NPs très riches en PEG hydrophile en comparaison aux NPs peu PEGylées. A l'inverse sur peau lésée, les NPs hydrophobes et négativement chargées de PLA seul ont permis la meilleure absorption du cholécalciférol. D'une part, la dynamique de la structure des NPs très PEGylées a permis une meilleure mouillabilité de la peau et une possible extraction de lipides cutanés, pouvant faciliter l'absorption sur peau intacte. D'autre part, la composition de la peau a conditionné la structure des NPs, puisque, sur peau lésée, les espèces ioniques libérées de la peau ont déstabilisé les NPs peu ou non PEGylées. Par adhésion à la surface de la peau, les agrégats de PLA ont pu ainsi faciliter l'absorption sur peau lésée.Lors du développement de formulations de NPs, leur composition chimique est donc à optimiser selon l'état pathologique de la peau / The design of clinically efficient polymeric nanoparticles (NPs) for skin drug delivery is based on the understanding of the influence of NPs chemical composition on their interactions with the skin tissue, notably the pathological skin. The aim of this work was to determine the influence of the hydrophilic component of polymeric NPs on the delivery of a lipophilic model drug (cholecalciferol).It was noticed that the polymeric hydrophilic composition of amphiphilic PLA-based NPs conditioned the NPs physico-chemical properties, notably in terms of size, surface properties, structure and drug protection. With regard to absorption into intact skin, the hydrophilic composition of 100 nm NPs had little impact. Only a slightly greater skin absorption was obtained from NPs with high hydrophilic PEG content compared to weakly PEGylated NPs. On the contrary in impaired skin, hydrophobic and negatively charged non-PEGylated NPs (PLA NPs) provided the best drug absorption. On the one hand, the dynamic structure of highly PEGylated NPs providing better skin wettability and potential skin lipids extraction may have contributed for increased absorption in intact skin. On the other hand, skin condition altered the NPs structure since it was observed that a non-negligible quantity of ionic species was released from impaired skin, triggering the destabilization of weakly or non-PEGylated charged NPs. However, only PLA aggregates sedimented/adhered onto the skin surface, which could have facilitated absorption in impaired skin. The polymeric hydrophilic composition of NPs and the pathological skin condition are therefore essential points to consider when designing nanoformulations

A nanotecnologia é uma ciência interdisciplinar onde se desenvolve nanomateriais para uso em diversas áreas como a farmácia, cosmética e agroindústria. Um de seus objetivos é aprimorar propriedades de ativos para novas aplicações, por exemplo, através de sistemas para liberação controlada através do uso de biomaterias. Dentre estes biomateriais destaca-se o poliácido lático (PLA) que é constantemente aplicado como matriz polimérica de várias nanoestruturas para o encapsulamento de ativos. Na área cosmética, ativos como os óleos essenciais são de grande interesse. O óleo essencial de pimenta rosa (Schinus molle L.) é composto por terpenos que apresentam, entre outras, atividade antioxidante e inseticida. No presente trabalho desenvolvemos um novo sistema de nanopartículas de PLA em solução aquosa, para liberação controlada do óleo essencial Schinus molle L. visando a utilização cosmética. As nanopartículas de PLA foram avaliadas quanto a estabilidade através da técnica de espalhamento dinâmico de luz (DLS). A formação foi estudada através do uso de difração de raios X (XRD) e espectroscopia vibracional (FTIR). A morfologia foi observada por microscopia eletrônica de varredura (SEM) comparando-se alguns dos resultados obtidos por DLS. Os resultados obtidos mostraram que o sistema é estável por aproximadamente 100 dias quanto ao tamanho, polidispersão e carga de superfície, mesmo com a variação de pH da solução em relação ao tempo. A estabilidade do nanossistema foi atribuída ao tensoativo dodecil sulfato de sódio (SDS), além da própria semicristalinidade e alta massa molar do PLA. Os componentes do sistema apresentaram interações químicas comprovadas por FTIR. O estudo por SEM mostrou que as nanopartículas obtidas têm aparência esférica, com a matriz polimérica contínua e com vários tamanhos constituindo assim um sistema polidisperso, como observadas também por DLS. A eficiência de encapsulação de 83% avaliada por calorimetria exploratória diferencial (DSC) e a liberação do ativo analisada por gravimetria mostraram-se satisfatórias. O sistema de nanopartículas obtido é estável e, por tanto, com potencial adequado para aplicação em produtos cosméticos. / Nanotechnology is an interdisciplinary science through which nanomaterials are developed for use in areas, such as pharmaceutical, cosmetology and agribusiness. One of its objectives is the improvement in the properties of active compounds for new applications by, for example, systems that use biomaterials for controlled release. Lactic polyacid (PLA), one of such biomaterials, has been constantly applied as a polymer matrix of various nanostructures for the encapsulation of active compounds. In cosmetics, active compounds, as essential oils are of great interest. The essential oil of pimenta rosa (Schinus molle L.) is composed of terpenes, which display antioxidant and insecticide activities. This dissertation addresses the development of a new system of PLA nanoparticles in an aqueous solution for the controlled release of essential oil Shinus molle L. to be applied to cosmetology. The stability of PLA nanoparticles was evaluated by dynamic light scattering (DLS). The formation of the system was studied by X-ray diffraction (XRD) and vibrational spectroscopy (FTIR) and its morphology and polydispersivity were verified by scanning electron microscopy (SEM), comparing some of the results obtained by DLS. The results show that the system is stable for approximately 100 days regarding size, polydispersion and surface charge, even when the pH of the solution varies over time. Stability was assigned to surfactant sodium dodecyl sulfate (SDS), PLA\'s semi crystallinity and high molecular weight. The chemical interactions of the system\'s components were evidenced by FTIR. SEM revealed spherical nanoparticles with a continuous polymeric matrix and polydispersivity, also observed by DLS. Satisfactory results were provided by the 83% of encapsulation efficiency calculated by differential scanning calorimetry (DSC) and the drug release analyzed by gravimetric technique. The nanoparticle system obtained is stable and, therefore, suitable for application to cosmetics.

A nanotecnologia é uma ciência interdisciplinar onde se desenvolve nanomateriais para uso em diversas áreas como a farmácia, cosmética e agroindústria. Um de seus objetivos é aprimorar propriedades de ativos para novas aplicações, por exemplo, através de sistemas para liberação controlada através do uso de biomaterias. Dentre estes biomateriais destaca-se o poliácido lático (PLA) que é constantemente aplicado como matriz polimérica de várias nanoestruturas para o encapsulamento de ativos. Na área cosmética, ativos como os óleos essenciais são de grande interesse. O óleo essencial de pimenta rosa (Schinus molle L.) é composto por terpenos que apresentam, entre outras, atividade antioxidante e inseticida. No presente trabalho desenvolvemos um novo sistema de nanopartículas de PLA em solução aquosa, para liberação controlada do óleo essencial Schinus molle L. visando a utilização cosmética. As nanopartículas de PLA foram avaliadas quanto a estabilidade através da técnica de espalhamento dinâmico de luz (DLS). A formação foi estudada através do uso de difração de raios X (XRD) e espectroscopia vibracional (FTIR). A morfologia foi observada por microscopia eletrônica de varredura (SEM) comparando-se alguns dos resultados obtidos por DLS. Os resultados obtidos mostraram que o sistema é estável por aproximadamente 100 dias quanto ao tamanho, polidispersão e carga de superfície, mesmo com a variação de pH da solução em relação ao tempo. A estabilidade do nanossistema foi atribuída ao tensoativo dodecil sulfato de sódio (SDS), além da própria semicristalinidade e alta massa molar do PLA. Os componentes do sistema apresentaram interações químicas comprovadas por FTIR. O estudo por SEM mostrou que as nanopartículas obtidas têm aparência esférica, com a matriz polimérica contínua e com vários tamanhos constituindo assim um sistema polidisperso, como observadas também por DLS. A eficiência de encapsulação de 83% avaliada por calorimetria exploratória diferencial (DSC) e a liberação do ativo analisada por gravimetria mostraram-se satisfatórias. O sistema de nanopartículas obtido é estável e, por tanto, com potencial adequado para aplicação em produtos cosméticos. / Nanotechnology is an interdisciplinary science through which nanomaterials are developed for use in areas, such as pharmaceutical, cosmetology and agribusiness. One of its objectives is the improvement in the properties of active compounds for new applications by, for example, systems that use biomaterials for controlled release. Lactic polyacid (PLA), one of such biomaterials, has been constantly applied as a polymer matrix of various nanostructures for the encapsulation of active compounds. In cosmetics, active compounds, as essential oils are of great interest. The essential oil of pimenta rosa (Schinus molle L.) is composed of terpenes, which display antioxidant and insecticide activities. This dissertation addresses the development of a new system of PLA nanoparticles in an aqueous solution for the controlled release of essential oil Shinus molle L. to be applied to cosmetology. The stability of PLA nanoparticles was evaluated by dynamic light scattering (DLS). The formation of the system was studied by X-ray diffraction (XRD) and vibrational spectroscopy (FTIR) and its morphology and polydispersivity were verified by scanning electron microscopy (SEM), comparing some of the results obtained by DLS. The results show that the system is stable for approximately 100 days regarding size, polydispersion and surface charge, even when the pH of the solution varies over time. Stability was assigned to surfactant sodium dodecyl sulfate (SDS), PLA\'s semi crystallinity and high molecular weight. The chemical interactions of the system\'s components were evidenced by FTIR. SEM revealed spherical nanoparticles with a continuous polymeric matrix and polydispersivity, also observed by DLS. Satisfactory results were provided by the 83% of encapsulation efficiency calculated by differential scanning calorimetry (DSC) and the drug release analyzed by gravimetric technique. The nanoparticle system obtained is stable and, therefore, suitable for application to cosmetics.

Made available in DSpace on 2014-12-17T14:16:27Z (GMT). No. of bitstreams: 1 AliceRO_DISSERT.pdf: 2104659 bytes, checksum: 208850f5293dd4764037ec4c490d3636 (MD5) Previous issue date: 2011-12-19 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / Methotrexate (MTX) is a drug used in the chemotherapy of some kind of cancers, autoimmune diseases and non inflammatory resistant to corticosteroids uveits. However, the rapid plasmatic elimination limits its therapeutic success, which leads to administration of high doses to maintain the therapeutic levels in the target tissues, occurring potential side effects. The aim of this study was to obtain spray dried biodegradable poly-lactic acid co-glycolic acid (PLGA) microparticles containing MTX. Thus, suitable amounts of MTX and PLGA were dissolved in appropriate solvent system to obtain solutions at different ratios drug/polymer (10, 20, 30 and 50% m/m). The physicochemical characterizing included the quantitative analysis of the drug using a validate UV-VIS spectrophotometry method, scanning electron microscopy (SEM), infrared spectrophotometry (IR), thermal analyses and X-ray diffraction analysis. The in vitro release studies were carried out in a thermostatized phosphate buffer pH 7.4 (0.05 M KH2PO4) medium at 37?C ? 0.2 ?C. The in vitro release date was subjected to different kinetics release models. The MTX-loaded PLGA microparticles showed a spherical shape with smooth surface and high level of entrapped drug. The encapsulation efficiency was greater then 80%. IR spectroscopy showed that there was no chemical bond between the compounds, suggesting just the possible occurrence of hydrogen bound interactions. The thermal analyses and X-ray diffraction analysis shown that MTX is homogeneously dispersed inside polymeric matrix, with a prevalent amorphous state or in a stable molecular dispersion. The in vitro release studies confirmed the sustained release for distinct MTX-loaded PLGA microparticles. The involved drug release mechanism was non Fickian diffusion, which was confirmed by Kornmeyer-Peppas kinetic model. The experimental results demonstrated that the MTX-loaded PLGA microparticles were successfully obtained by spray drying and its potential as prolonged drug release system. / O metotrexato (MTX) ? um f?rmaco utilizado na quimioterapia de alguns tipos de c?ncer, doen?as autoimunes e uve?tes n?o inflamat?rias resistentes aos corticoster?ides. No entanto, sua r?pida elimina??o plasm?tica limita o sucesso terap?utico, levando ? necessidade de altas doses para manuten??o da concentra??o efetiva no tecido alvo, ocasionando o potencial surgimento de rea??es adversas. O objetivo principal desse estudo foi obter um sistema microparticulado biodegrad?vel ? base de ?cido poli (?cido l?tico-co-?cido glic?lico) (PLGA) por spray drying para libera??o prolongada do MTX. Para isso, quantidades distintas de MTX e PLGA foram dissolvidas em sistema solvente adequado para obter solu??es com diferentes propor??es de f?rmaco em rela??o ao pol?mero (10, 20, 30 e 50% m/m). A caracteriza??o f?sicoqu?mica incluiu an?lise quantitativa do f?rmaco incorporado na matriz polim?rica por espectrofotometria UV-VIS em 303nm previamente validada, microscopia eletr?nica de varredura (MEV), espectrofotometria de infravermelho (IV), an?lises t?rmicas e difra??o de raios-X (DRX). O perfil de libera??o in vitro do f?rmaco nas micropart?culas foi realizado em tamp?o fosfato (0.05 M KH2PO4) em banho termostatizado 37 ?C ? 0.2 ?C. Os dados obtidos do estudo de libera??o in vitro foram submetidos a diferentes modelos cin?ticos de libera??o. As micropart?culas de PLGA contendo o MTX apresentaram a forma esf?rica, uniforme, com superf?cie aparentemente lisa. O n?vel de efici?ncia de encapsula??o foi superior a 80%. A espectroscopia na regi?o do infravermelho demonstrou que n?o ocorreu liga??o qu?mica entre os componentes dos sistemas, no entanto foi observado forte intera??o entre o MTX e PLGA indicando prov?vel ocorr?ncia de pontes de hidrog?nio. An?lise XII t?rmica e DRX demonstraram que o MTX est? distribu?do na matriz polim?rica com a preval?ncia do estado amorfo ou em dispers?o molecular. O estudo de libera??o in vitro confirmou o perfil de libera??o prolongada para as diferentes micropart?culas. O mecanismo de libera??o envolvido foi por difus?o n?o Fickiana, ao qual foi determinado a partir do modelo cin?tico de Kornmeyer- Peppas. Os resultados experimentais demonstraram o sucesso na obten??o das micropart?culas de PLGA contendo o MTX por spray drying e seu potencial como sistema de libera??o prolongada do f?rmaco.

L'objectif de cette thèse était de mettre en oeuvre le développement d'une thérapie des plaies cutanées profondes basée sur l'utilisation de nanoparticules (NP) biodégradables de poly(acide lactique) (NP-PLA) vectrices de médiateurs de la cicatrisation. Le but était d'accélérer la cicatrisation cutanée et de favoriser la reconstruction d'un derme fonctionnel. La méthode a été de (i) réduire la réaction inflammatoire pour en contenir les effets délétères et (ii) stimuler la réépithélialisation pour accélérer la cicatrisation et réduire le risque infectieux. Les moyens ont été l'utilisation d'un antioxydant, la vitamine E (VE) et d'un facteur de croissance des fibroblastes (le FGF2) vectorisés par des nanoparticules biocompatibles et biodégradables de poly(acide lactique) (PLA). Nos NP-PLA contiennent l'antioxydant (VE) dans leur coeur hydrophobe, et portent le facteur de croissance fibroblastique (FGF2) à leur surface. Ces formulations ont été (i) caractérisées par des méthodes physico-chimiques et (ii) testées par des méthodes in vitro pour évaluer leurs effets potentiels, en tant que système de délivrance de VE et de FGF2, sur la cicatrisation des plaies. Des modèles expérimentaux in vivo ont été développés et caractérisés pour mettre en évidence l'efficacité des NP-PLA fonctionnalisées pour la cicatrisation cutanée et la reconstruction dermique fonctionnelle. Nos résultats montrent que l'activité antioxydante de la VE n'est pas perturbée par l'encapsulation dans des NP-PLA et qu'elle est légèrement supérieure à celle de la VE libre dans un système in vitro. De même, l'activité biologique du FGF2 sur la prolifération et la migration des fibroblastes dans un système in vitro n'est pas altérée par son adsorption sur des NP-PLA. Aucune de ces deux NP-PLA fonctionnalisées n'a de cytotoxicité avérée in vitro. Deux modèles expérimentaux de plaies cutanées profondes ont été développés sur souris sans poils SKH1 saines : (i) Un modèle robuste de brûlure cutanée thermique de 3ème degré qui se caractérise par une inflammation massive de la plaie et par un stade de granulation tardif après 16 jours de cicatrisation. (ii) Un modèle de plaie d'excision cutanée a également été utilisé. Un modèle de cicatrisation retardée a été obtenu par induction chimique d'un diabète de type I stable avant réalisation des plaies d'excision ou de brûlure. Ces modèles de plaies cutanées ont été caractérisés tout au long du processus de cicatrisation par des études (i) macroscopiques de cinétique de fermeture des plaies, (ii) histologiques d'inflammation, de nécrose et de réépithélialisation, (iii) physiologiques de perfusion sanguine cutanée. L'expression de 84 gènes impliqués dans le processus de cicatrisation a été étudiée sur le tissu cicatriciel 14 jours après formation de la plaie. Pour conclure, nos résultats mettent en évidence le potentiel de vectorisation de molécules thérapeutiques des NP de PLA pour le développement de futures stratégies de délivrance ciblée de VE et de FGF2 dans les plaies cutanées profondes. Les modèles expérimentaux in vivo développés et caractérisés, ouvrent la voie aux études précliniques d'efficacité des NP-PLA fonctionnalisées dans le processus de cicatrisation des plaies profondes / The objective of this thesis was to develop a therapy of cutaneous deep wounds based on biodegradable poly (lactic-acid) nanoparticles (PLA-NP) releasing wound healing mediators. The goal was to accelerate wound healing and to promote the reconstruction of a functional dermis. Our method was (i) to reduce the inflammatory reaction in the aim of limiting its deleterious effects, (ii) to stimulate reepithelialization to accelerate wound healing and to reduce the risk of infections. The implementation of means was based on the use of an antioxidant (vitamin E, VE) and a fibroblast growth factor (FGF2) carried by biocompatible and biodegradable poly(lactic-acid) based nanoparticles. Our PLA-NP contained the antioxidant (VE), in their hydrophobic core and carried the fibroblastic growth factor (FGF2) on their surface. These formulations were (i) characterized by physico-chemical methods and (ii) tested by in vitro methods to evaluate their effects as a delivery system of VE and FGF2 on wound healing. Experimental in vivo models have been developed and characterized in the aim of studying the potential beneficial effect of functionalized PLA-NP on wound healing and functional reconstruction of dermis. Our results show that the antioxidant activity of VE was not inhibited by encapsulation into PLA-NP and was lightly increased compared with free VE in an in vitro system. The biological activity of FGF2 on proliferation and migration of fibroblasts in an in vitro system was not altered by adsorption onto PLA-NP as well. No cytotoxicity of these functionalized PLA-NP was detected in vitro. Two experimental models of deep cutaneous wounds were developed on the healthy SKH1 hairless mouse: (i) A robust third degree thermal burn model that was characterized by massive inflammation of the wound and a late granulation stage after 16 days of healing. (ii) A model of excisional skin wound was also used. A model of delayed wound healing was established by chemical induction of stable type I diabetes prior to excision and burn injuries. The healing process of these models of cutaneous wounds was characterized by (i) macroscopic studies of wound closure, (ii) histological studies of inflammation, necrosis and reepithelialization, and (iii) by physiological studies of cutaneous blood perfusion. A study of the expression of 84 genes involved in the healing process was carried out on the scar tissue 14 days post-wound. In conclusion, our results highlight the potential efficacy of PLA-NP as a vector of therapeutic molecules for the development of future strategies for targeted delivery of VE and FGF2 in deep skin wounds. The developed and characterized in vivo experimental models open the way to preclinical studies of efficacy of functionalized PLA-NP on the healing process of deep wounds