TY - JOUR
T1 - Pulmonary delivery of siRNA-loaded lipid-polymer hybrid nanoparticles: Effect of nanoparticle size
AU - Wadhwa, Abishek
AU - Bobak, Thomas R.
AU - Bohrmann, Lennart
AU - Geczy, Reka
AU - Sekar, Sathiya
AU - Sathyanarayanan, Gowtham
AU - Kutter, Jörg P.
AU - Franzyk, Henrik
AU - Foged, Camilla
AU - Saatchi, Katayoun
AU - Häfeli, Urs O.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1016/j.onano.2023.100180
DO - 10.1016/j.onano.2023.100180
M3 - Journal article
VL - 13
JO - OpenNano
JF - OpenNano
SN - 2352-9520
M1 - 100180
ER -