Optimizing nanoparticles for in vivo applications

For several years, Lawrence Livermore has been developing a novel class of nanoparticles for biomedical applications that are highly biocompatible and offer advantages that other nanoparticle types do not. These nanoparticles, termed nanolipoprotein particles (NLPs), consist of a phospholipid bilayer stabilized by an apolipoprotein scaffold protein and are lab-made versions of HDL, or “good cholesterol,” that are used by the body to transport cholesterol and triglycerides in the blood. While preliminary studies had previously demonstrated that the type of phospholipid used to synthesize these particles can affect their stability, it was unclear how specific phospholipid features impact the nanoparticle stability under physiologically relevant conditions.

An LLNL team led by Nick Fischer (BBTD) recently conducted a thorough assessment of how phospholipid structure impacts stability of biomimetic nanoparticles. This information has important implications for using these NLPs in vivo and would provide insight into how to tune the particle stability for applications ranging from diagnostics to drug delivery. This study assessed the stability of NLPs with varying lipid compositions in blood serum at 37°C, closely mimicking the environment and conditions the particles would encounter circulating in the bloodstream.

Experimental results of NLP disassembly under these conditions were then correlated to intrinsic lipid characteristics that were measured through molecular dynamics simulations for each of the tested formulations. The results demonstrated that the elasticity of the lipid bilayer, but not lipid surface area or thickness, is a significant indicator of particle instability in the body. These studies provide a foundation for subsequent optimization of NLP composition to tailor the stability for the particular in vivo application.

This work was supported by the Laboratory Directed Research and Development Program (15-LW-023 and 17-LW-051).

[S.F. Gilmore, T.S. Carpenter, H.I. Ingólfsson, S.K.G. Peters, P.T. Henderson, C.D. Blanchette, and N.O. Fischer, Lipid composition dictates serum stability of reconstituted high-density lipoproteins: implications for in vivo applications, Nanoscale, available online on March 22, 2018, doi: 10.1039/C7NR09690A.]