(438f) Tuning the Hydrophilicity of Albumin for Targeting Lipid Nanoparticles

Both albumin-based and lipid-based nanoparticle systems have gained considerable interest as promising vectors for drug delivery. Albumin is a biodegradable, nontoxic, and nonimmunogenic protein with high stability, the ability to passively transport hydrophobic drugs, sensitivity to multiple cellular receptors, and many surface moieties that can be conjugated for improved targeting capabilities. Lipid nanoparticles have proven to be highly effective and versatile at transporting delicate therapeutics and can exhibit high bioavailability. A modified lipid nanoparticle that incorporates albumin can exploit the benefits of both to create a stable formulation for targeted drug delivery with decreased cytotoxicity. However, the high hydrophilicity of albumin makes incorporation of the protein into the lipid nanoparticle structure non-trivial, and the naked protein has limited capabilities to target specific tissues. To remedy both issues, this research seeks to conjugate bovine serum albumin with a lipophilic moiety, which allows for incorporation of the protein into the phospholipid outer layer of lipid nanoparticles. This moiety also serves as a targetable ligand for immobilization of cell-targeting molecules such as antibodies. Here we report studies of nanoparticle stability over time in biosimilar conditions, morphology assessment, and numerical analysis of changes to albumin hydrophilicity varying with conjugation extent.