In our recent manuscript entitled “On the structure of solid lipid nanoparticles“, we have combined large-scale all-atom molecular dynamics simulations and small angle neutron scattering (SANS) experiments to provide the first detailed description of the internal structure and atomistic interactions which govern this structure of liquid and solid lipid aggregates, as well as solid lipid nanoparticles. Solid lipid nanoparticles (SLNs), which are made up of a crystalline lipid core and an interfacial layer of surfactants that stabilise the lipid core, have garnered a lot of attention as drug delivery vehicles since their ability to encapsulate and release small molecules can be tailored through the selection of lipids and surfactants used in making them. One challenge that is present in developing SLNs as a commercially viable drug delivery technology is their instability. This instability, at least partially, results from the tendency of the lipid core to first crystallise in the least ordered, metastable α-form, but then slowly transform into the more ordered, more stable β-form. During this transition, the lipid molecules in the core of the SLN rearrange and the shape of the nanoparticle changes from spherical (α-form) to elongated (β-form). Additionally, the transition to the more ordered β-form results in defects of the packing in the lipid core, where lipophilic therapeutic agents generally sit, disappear, and as a result the therapeutic agents can be expelled from the SLN during storage or administration.
In collaboration with Jayne Lawrence’s group at the University of Manchester, we present the first description of molecular-scale mechanisms that are important within regards to the formation and morphology of a SLN comprising of the triglyceride, tripalmitin, and the nonionic surfactant, Brij O10. We also determined the difference in the structure and conformation of the lipids in solid lipid and liquid lipid aggregates. Finally, we demonstrated how the Brij O10 surfactant affects the conformation of the tripalmitin molecules within the solid lipid core, as well as the overall morphology of the nanoparticle.
Full reference: “On the structure of solid lipid nanoparticles,” Demi L. Pink, Orathai Loruthai, Robert M. Ziolek, Prawarisa Wasutrasawat, Anne E. Terry, M. Jayne Lawrence & Christian D. Lorenz. Small (2019) 15 (45), 1903156.