Compression of Vectors for Small Interfering RNAs Delivery: Toward Oral Administration of siRNA Lipoplexes in Tablet Forms

• DOI: 10.1021/acs.molpharmaceut.9b01190
• Publication Date: 2020-03-03T19:11:01Z
• Authors: Virginie Busignies; Danielle Campiol ...; Christine Charrueau; Marcela Coelho Si...; Anne-Marie Lachagès; Angelo Malachias; Stéphanie Finet; Asad Ur Rehman; Pascal Bigey; Pierre Tchoreloff; Virginie Escriou
• Keywords: Small-angle X-ray scattering

Currently, most nonviral nucleic acid vectors are in the form of colloidal suspensions administered primarily parenterally. This type formulation and mode administration impose strong constraints such as size or production sterile preparations. The tablet provides access to easy oral administration, well accepted by patients; As regards vectors, a dry represents an advance terms stability. Using optimized lipid-based small interfering RNA-delivery system, we studied tabletability liquid suspension these vectors. We conditions freeze-drying choosing excipients process, allowing for conservation both gene-silencing efficacy formulated siRNAs supramolecular structure lipid particulate system. Gene-silencing was assayed on luciferase-expressing cells siRNA vector freeze-dried forms examined using small-angle X-ray scattering (SAXS) synchrotron radiation. powders were then mixed with necessary good progress compression regular supply matrix reduction friction. carried out rotary press simulator that allows complete monitoring conditions. After compression, retained more than 60% their efficacy. Within tablets, specific SAXS signal detectable lamellar cubic phases initial restored after resuspension disintegration tablets. These results show bilayer structures particles preserved despite mechanical imposed compression. If result could be expected step, it never shown, our knowledge, siRNA-delivery systems retain stress opens promising perspectives alternative parenteral administration.