Probing interactions between sponge phase lipid nanoparticles and supported lipid bilayers

Lipid nanoparticles (LNPs) have garnered interest in making biopharmaceuticals with tailored cellular uptake and delivery mechanisms. LNPs, commonly internalized by cells via endocytic pathways or macropinocytosis, offer versatile avenues for drug delivery. Certain LNPs, particularly those exhibiting fusogenic properties, possess the capability to fuse with the cell membrane, facilitating the release of encapsulated payloads into the cellular cytoplasm. This attribute holds promise for enhancing the bioavailability of encapsulated proteins. Our previous studies focused on developing sponge phase nanoparticles (L3) using 1,2-dioleoyl-sn-glycero-3-phosphocholine, glycerol monooleate, and polysorbate 80. We have successfully encapsulated myoglobin using these nanoparticles leveraging their structure which comprises a network of water cavities and curved bilayers. X-ray scattering of the loaded LNPs showed inclusion of myoglobin has negligible impact on nanoparticle architecture. Results from Quartz Crystal Microbalance (QCM-D) elucidated transient interactions between these LNPs and myoglobin. This work aims to employ neutron reflectometry to scrutinise molecular exchange and dynamics occurring at the interface between the nanoparticle and supported lipid bilayer. Additionally, investigations will delve into the destiny of the encapsulated protein post-injection. Given the inherent fluidity of L3, their susceptibility to fusion with lipid bilayers warrant investigation.