Chemical and structural investigation of lipid nanoparticles: drug–lipid interaction andmolecular distribution

Abstract

Lipid nanoparticles are a promising alternative to existing carriers in chemical or drugdelivery systems. A key challenge is to determine how chemicals are incorporated anddistributed inside nanoparticles, which assists in controlling chemical retention and releasecharacteristics. This study reports the chemical and structural investigation ofγ-oryzanol loading inside a model lipid nanoparticle drug deliverysystem composed of cetyl palmitate as solid lipid and Miglyol812® as liquid lipid. The lipid nanoparticles were prepared by high pressurehomogenization at varying liquid lipid content, in comparison with theγ-oryzanol free systems. The size of the lipid nanoparticles, as measured by thephoton correlation spectroscopy, was found to decrease with increased liquid lipidcontent from 200 to 160 nm. High-resolution proton nuclear magnetic resonance (1H-NMR) measurements of the medium chain triglyceride of the liquid lipid has confirmedsuccessful incorporation of the liquid lipid in the lipid nanoparticles. Differential scanningcalorimetric and powder x-ray diffraction measurements provide complementary results to the 1H-NMR, whereby the crystallinity of the lipid nanoparticles diminisheswith an increase in the liquid lipid content. For the distribution ofγ-oryzanol inside the lipidnanoparticles, the 1H-NMR revealed that the chemical shifts of the liquid lipid inγ-oryzanol loaded systems were found at rather higher field than those inγ-oryzanol free systems, suggesting incorporation ofγ-oryzanol in the liquid lipid. In addition, the phase-separated structure was observedby atomic force microscopy for lipid nanoparticles with 0% liquid lipid, butnot for lipid nanoparticles with 5 and 10% liquid lipid. Raman spectroscopicand mapping measurements further revealed preferential incorporation ofγ-oryzanol in the liquid part rather than the solid part of in thelipid nanoparticles. Simple models representing the distribution ofγ-oryzanol and lipids (solid and liquid) inside the lipid nanoparticle systems are proposed.