Thermotropic effects of PEGylated lipids on the stability of HPPH-encapsulated lipid nanoparticles (LNP)

In this work, we demonstrate the enhanced thermal and steric stability of lipid-based formulations in the presence of encapsulated HPPH that have demonstrated potential cancer applications in previously presented in vivo studies. Differential scanning calorimeter (DSC) was used to study the phase transitions, and domain formations, and to qualify the thermodynamic properties associated with change in lipid bilayer behavior due to the presence of PEGylated at varying concentrations and sizes, and the encapsulated HPPH molecules. Thermal instability was quantified by dramatic changes in calculated enthalpy, and the shape of the melting peak or calculated half width of melting peak. This systematic study focused on understanding the effects of varying molecular mass and concentrations of PEG polymers in the photopolymerizable lipid DC(8, 9)PC lipid bilayer matrix for four weeks at room temperature of 25 °C. The major findings include increased thermal stability of the lipid bilayer due to the presence of PEG-2 K and the HPPH that resulted from the van der Waals forces between various molecular species, and the change in bilayer curvature confirmed via mathematical correlations. It is demonstrated that the encapsulation of therapeutics in lipid formulations can alter their overall thermal behavior, and therefore, it is imperative to consider calorimetric effects while designing lipid-based vaccines. The presented research methodologies and findings presented can predict the stability of lipid-based vaccines that are under development such as COVID-19 during their storage, transport, and distribution.