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Nano and Micro Technologies

Nano and Micro Technologies - Poster Session D

Poster J14 - Nanoparticle Development For siRNA Delivery To Treat Osteoarthritis

Friday, October 25, 2024
3:30 PM - 4:30 PM EST
Location: Exhibit Hall E, F & G

Introduction:  Osteoarthritis (OA) is a degenerative joint disease that affects over 32 million US adults and currently has no cure; treatments for OA focus on alleviating symptoms and include lifestyle changes, pain-relieving medications, and joint replacements. Short interfering RNA (siRNA) has the capability to degrade protein-producing mRNA, which can be used in OA to prevent the expression of the gene that drives cartilage degradation and ultimately inhibit disease progression. However, siRNA delivery is challenging in vivo due to issues such as endosomal escape and kidney clearance. One alternative method of delivery is loading the siRNA into polymeric nanoparticles (si-NPs) that enable siRNA to be delivered into the cell. The purpose of this project was to optimize nanoparticle formulation using a confined impinging jets mixer (CIJ) for effective siRNA delivery.

Materials and

Methods:  Various formulations of si-NPs were made using a CIJ mixer with solvent and antisolvent streams. The si-NPs contained a core consisting of poly(dimethylaminoethyl methacrylate-co-butyl methacrylate) (DB) to enable endosomal escape and poly(lactide-co-glycolide) (PLGA) for nanoparticle stability. DSPE-PEG (lipid-PEG) was used as a surfactant for biocompatibility and to prevent si-NP aggregation. The ratio of DB to PLGA in the si-NP core was varied, as well as the ratio of amines to phosphates (N:P), in order to optimize the gene silencing activity and toxicity of the si-NPs.

Results, Conclusions, and Discussions: The si-NPs were analyzed for size, zeta potential, and siRNA delivery capability. The formulation concentrations of 3 mg/mL of DB and PLGA in the solvent stream and 1 mg/mL lipid-PEG in the antisolvent stream were found to be the most successful for nanoparticle formation using the CIJ mixer. A luciferase knockdown was performed to observe which formulation was most successful at gene knockdown. It was determined that luciferase NPs with a core composition of 50% DB and an N:P ratio of 5 were most uniform, viable, and effective at luciferase knockdown.

Acknowledgements (Optional):  This project was funded by the NSF-DMR 1852157 grant. Special thanks to VINSE and members of the Duvall Advanced Therapeutics Laboratory for their support and guidance.