Conclusion

Les systèmes pour la délivrance locale et prolongée de principes actifs (PA) sont en constante évolution

depuis ces 30 dernières années, afin d’améliorer l’efficacité thérapeutique de l’actif encapsulé, et de

rendre le traitement moins contraignant pour le patient. Les hydrogels se sont avérés être d’excellents

candidats pour servir de plateforme à la délivrance de PA. Avec le développement d’hydrogels plus

sophis-tiqués, comme les hydrogels hybrides, les hydrogels double réseaux, et les hydrogels clics, les possibilités

de moduler leur porosité et ainsi la cinétique de libération du PA encapsulé sont infinies. Dans cet état de

l’art, des exemples de ces systèmes sophistiqués préparés à partir de chitosane ont été plus

particulière-ment présentés.

65

Ces travaux de thèse ont pour objectif de développer de nouveaux DDS capables de délivrer de façon

locale, et prolongée un PA hydrophobe. Pour retarder la libération du PA et pouvoir encapsuler un principe

actif hydrophobe, notre stratégie a été de d’explorer la double encapsulation, en solubilisant le PA

hydro-phobe dans des nanoparticules lipidiques (LNPs), elles mêmes intégrées dans les hydrogels. En s’appuyant

sur l’état de l’art rapporté dans ce chapitre, nous avons préparé des hydrogels hybrides à partir de 2 pol

y-saccharides, la CMC, et le chitosane, mélangé avec du PEG et réticulés par chimie clic. Ces systèmes sont

originaux de part leur mise en forme et les chimies développées pour les réticuler.

Des hydrogels hybrides de CMC/PEG, intégrant des LNPs, ont d’abord été préparés et réticulés par chimie

radicalaire thiol-ène. Les nouvelles propriétés de l’hydrogel composite ainsi que la stabilité des LNPs dans

ce matériau ont été étudiées. Le design du système a permis de moduler la cinétique de libération des

LNPs depuis les gels (chapitre 2). Un fluorophore encapsulé dans le cœur des LNPs sert de modèle pour

étudier la cinétique de libération du principe actif depuis ces systèmes.

A partir des résultats de l’étude approfondie des hydrogels composites de CMC/PEG + LNPs, de nouveaux

systèmes plus faciles à manipuler ont été développés. De part ses propriétés biologiques et les multiples

mises en forme possibles qu’il offre, le chitosane a été utilisé pour préparer des films et des éponges

hy-brides. Les films de chitosane seront décrits dans le chapitre 3. Les propriétés des éponges ainsi que la

stabilité des LNPs dans ce matériau seront étudiées dans le chapitre 4.

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Les hydrogels de

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