Effect of Functional Groups in Lipid Molecules on the Stability of Nanostructured Lipid Carriers: Experimental and Computational Investigations

Lipid nanoparticles have been used as drug carriers for decades. Many lipid types have been screened for both solid lipid nanoparticles and nanostructured lipid carriers (NLCs). Specifically, for NLCs that are composed of lipids in the solid form mixed with lipids in the liquid form, compatibility of lipid combination and phase behavior play a significant role in the NLC quality. In this study, stearic acid (STA) and cetyl palmitate (CTP) were used as solid lipids, and oleic acid (OLA), isopropyl palmitate (IPP), and caprylic/capric triglycerides were used as liquid lipids. NLCs were prepared at solid:liquid ratios of 50:50, 70:30, and 90:10, respectively. The characteristics and stability of the prepared NLCs were investigated. Laboratory results showed that the solid lipid had a greater influence on the particle size than the liquid lipid. Meanwhile, cetyl palmitate, an ester compound, provides higher NLC stability compared to stearic acid, a carboxylic acid compound. A MARTINI-based coarse-grained molecular dynamics simulation was used to simulate the lipid droplet in water. The distribution of lipid molecules in the droplet was characterized by the polar group density distribution. Different spatial arrangements of the lipid headgroup and lipid molecules, when CTP or STA was used as solid lipids, might contribute to the different stabilities of prepared NLCs. The understanding of mixed lipid systems via simulations will be a significant tool for screening the type of lipids for drug carriers and other pharmaceutical applications.