Neil Forbes, Marta Morais, Kerry Carr, Benjamin Moshi & Elena Galfre
Phillips Medisize, 1-6 Prospect West, Bumpers Way, Chippenham SN14 6FH, United Kingdom
Summary
Lipid nanoparticles (LNPs) are proven vesicles for nucleic acid delivery and present a unique opportunity as adjuvant systems for intranasal vaccination. The formulation composition influences critical attributes of the particles, including size, charge and overall robustness. This study explores how PEGylated lipid impacts upon critical quality attributes (CQAs) of both cationic and ionizable LNPs, and how syringe nasal device actuation affects these attributes.
Results show that actuation using the Aptar Pharma’s LuerVax™ nasal nozzle and off-the-shelf syringe had minimal impact on particle size, regardless of formulation composition. Cationic (DOTAP) formulations demonstrated improved poly(A) encapsulation efficiency (EE%) and mass balance (%) compared to the neutral ionizable counterparts (ALCs) following actuation, potentially due to the constant positive charge maintaining electrostatic association. Increasing PEG content generally improved poly(A) content of the vesicles post-actuation, regardless of whether DOTAP or ALC was used. All PEGylated DOTAP formulations, and the higher PEG content ALC formulation showed delivered doses comparable to the marketed intramuscular vaccine SpikeVax™ (0.1 mg/mL), with 23–24 µg of poly(A) being delivered using the LuerVax device. Finally, aerosol characterization was conducted on the DOTAP formulations, demonstrating suitability as an intranasal product, with low %<10 µm droplets generated.