Pulmonary delivery of siRNA-loaded lipid-polymer hybrid nanoparticles: Effect of nanoparticle size
Abishek Wadhwa,
Thomas R. Bobak,
Lennart Bohrmann,
Reka Geczy,
Sathiya Sekar,
Gowtham Sathyanarayanan,
Jörg P. Kutter,
Henrik Franzyk,
Camilla Foged,
Katayoun Saatchi,
Urs O. Häfeli
Affiliations
Abishek Wadhwa
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Thomas R. Bobak
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Lennart Bohrmann
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Reka Geczy
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Sathiya Sekar
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Gowtham Sathyanarayanan
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Jörg P. Kutter
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Henrik Franzyk
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Camilla Foged
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
Katayoun Saatchi
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Urs O. Häfeli
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Corresponding author at: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Nanomedicines based on nanoparticles rely both on the potency of the drug as well as the efficiency of the delivery system, for which particle size plays a crucial role. For the intracellular delivery of small interference RNA (siRNA), lipid-polymer nanoparticle (LPN) hybrid systems constitute a safe and highly effective class of delivery systems. In the present study, we employ a microfluidics method for the manufacturing of spherical siRNA-loaded LPNs for pulmonary delivery with distinct size distributions with average diameters of approximately 70, 110, and 220 nm. We designed an optically clear, inexpensive thiol-ene polymeric microfluidic chip prototype that is compatible with standard ‘soft-lithography’ techniques, allows for replica molding, and is resistant to harsh solvents. By using SPECT/CT in vivo imaging, we show comparable pulmonary clearance patterns of all three differently sized LPN formulations following intratracheal administration. Also, negligible accumulation in the liver was observed.
