title: Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes: Towards a vaginal sustained released system for siRNA.
abstract: 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, deformability 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.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liege, 4000, Belgium. Electronic address: tania.furst@ulg.ac.be.
authors.forename: Tania
authors.initials: T
authors.lastname: Furst
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Ghent Research Group on Nanomedicines, Ghent University, 9000, Belgium.
authors.forename: George R
authors.initials: GR
authors.lastname: Dakwar
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Ghent Research Group on Nanomedicines, Ghent University, 9000, Belgium.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zagato
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liege, 4000, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Lechanteur
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Ghent Research Group on Nanomedicines, Ghent University, 9000, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Remaut
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liege, 4000, Belgium.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Evrard
authors.affiliation: Laboratory of General Biochemistry and Physical Pharmacy, Ghent Research Group on Nanomedicines, Ghent University, 9000, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Braeckmans
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, University of Liege, 4000, Belgium.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Piel
mesh_terms: D000268:Adhesiveness; D000282:Administration, Intravaginal; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002518:Ceramides / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005260:Female; D005612:Freeze Drying; D018014:Gene Transfer Techniques; D006801:Humans; D020100:Hydrogels; D008081:Liposomes / Q000737:chemistry*; D009092:Mucous Membrane / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties; D014621:Vagina / Q000187:drug effects*
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D002518:Ceramides; D020100:Hydrogels; D008081:Liposomes; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D002482:Cellulose; C002283:hydroxyethylcellulose
keywords: Diffusion; Freeze-drying; Lipoplexes; Mucoadhesion; Stability; Vaginal drug delivery