[en] Topical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. To minimize adhesive interactions with vaginal mucus components, lipoplexes were coated with different derivatives of polyethylene glycol: DPSE-PEG2000, DPSE-PEG750 and ceramide-PEG2000. Based on stability and diffusion properties
in simulated vaginal fluids, lipoplexes containing DSPE-PEG2000 were selected and incorporated in hydroxyethyl cellulose (HEC) hydrogels. Solid systems, called sponges, were then obtained by freeze-drying. Sponges meet acceptable mechanical characteristics and their hardness, eformability and mucoadhesive properties are not influenced by the presence of lipoplexes. Finally, mobility and stability of lipoplexes inside sponges rehydrated with vaginal mucus, mimicking in
situ conditions, were evaluated by advanced fluorescence microscopy. The release rate was found to be influenced by the HEC concentration and consequently by the viscosity after rehydration.
This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina.
Research center :
Centre Interfacultaire de Recherche du Médicament - CIRM
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Furst, Tania ; Université de Liège > Département de pharmacie > Pharmacie galénique
Dakwar, George R.; Ghent University > Ghent Research Group on Nanomedicines
Zagato, Elisa; Ghent University > Ghent Research Group on Nanomedicines
Lechanteur, Anna ; Université de Liège > Département de pharmacie > Pharmacie galénique
Remaut, Katrien; Ghent University > Ghent Research Group on Nanomedicines
Evrard, Brigitte ; Université de Liège > Département de pharmacie > Pharmacie galénique
Braeckmans, Kevin; Ghent University > Ghent Research Group on Nanomedicines
Piel, Géraldine ; Université de Liège > Département de pharmacie > Pharmacie galénique
Language :
English
Title :
Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA
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