NSTI Nanotech 2009

A nanoparticle approach for effective RNAi delivery

M.F. Rauch, E. Ferreira, J. Lu, C. Weller, K. Woodrow, M. Cartiera, W.M. Saltzman
Carigent Therapeutics, Inc., US

Keywords: nanoparticles, RNA interference, siRNA, PLGA

Abstract:

RNA interference (RNAi) holds great promise for treating genetic disorders, infectious diseases, and cancer. However, RNAi’s potential use in vivo has been limited by challenges associated with RNAi delivery. To overcome these delivery challenges, we have fabricated surface-modified poly(lactic-co-glycolic) acid (PLGA) nanoparticles for RNAi delivery. Our nanoparticle platform promotes high encapsulation of several RNAi materials. Our surface-modification technology which incorporates an avidin-biotin system promotes the addition of a variety of ligands including antibodies, cell penetrating peptides, and polyethylene glycol. Our manufacturing process allows for reproducible nanoparticles with low polydispersity, an average diameter of approximately 150 nm, and sustained release of siRNA. Evaluation of our particles in vitro suggests that high loadings of siRNA, nanoparticle size, and targeting promotes enhanced particle uptake into a variety of cell lines. We have observed efficient knockdown of protein with low amounts of siRNA. Ultimately, these targeted nanoparticles have great potential for in vivo disease models. In related studies, we have shown that non-surface-modified nanoparticles are as active as cationic lipids after topical delivery to the female reproductive tract in mice. Preliminary results also indicate that our siRNA-loaded nanoparticles have excellent activity after intratumoral or subcutaneous injection.
 
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