Vibrational spectroscopy of self-forming synthetic PEGylated lipids and nanovesicles

Vibrational spectroscopy has been used to elucidate the structure and conformation of lipids and nanovesicles. In this study, three different vibrational spectroscopic techniques, namely near-infrared (NIR), Fourier transform infrared (FTIR) and Raman spectroscopies, have been employed for the comprehensive investigation of newly developed self-forming synthetic PEGylated lipids, trademarked as QuSomes. In contrast to conventional phospholipids, these new kind of lipids spontaneously form liposomes or nanovesicles upon hydration, without the supply of external activation energy. The amphiphiles considered in this study differ in their hydrophobic hydrocarbon chain length and contain different units of polyethylene glycol (PEG) hydrophilic headgroups. Such lipids are composed of 1,2-dimyristoyl-rac-glycerol-3-dodecaethylene glycol (GDM-12), 1,2-dioleoyl-rac-glycerol-3-dodecaethylene glycol (GDO-12) and 1,2-distearoyl-rac-glycerol-3-triicosaethylene glycol (GDS-23). The NIR absorption spectra of these new artificial lipids have been recorded by using a novel miniaturized dual-detector micro-mirror spectrometer based on micro-opto-electro-mechanical systems (MOEMS) technology. Similarly, FTIR and Raman spectroscopic techniques have been used to establish the "molecular fingerprint" of these lipids. In addition, laser tweezers Raman spectroscopy (LTRS) has been utilized to optically trap and manipulate single lipid nanoparticles and nanovesicles. Likewise, fluorescence correlation spectroscopy (FCS) has been employed to determine the size distribution of those nanovesicles in suspension.;This work focused on the study of thermotropic phase behaviors and associated changes in the conformational order/disorder of such lipids and nanovesicles in suspensions. For this purpose, variable-temperature sample holders have been designed and were employed to acquire the temperature-dependence infrared and Raman spectra of these lipids and nanovesicles in the temperature range of -4 to 110°C. Phase transition temperature profiles have been deduced by either monitoring the shifts in the vibrational peak positions or plotting vibrational peak intensity ratios in the C-H stretching region as a function of temperature. Furthermore, several spectral indicators have been deduced and correlated with various aspects of molecular structure as well as intramolecular motion and intermolecular interactions. Finally, to supplement our observations of phase transformations, a thermodynamic approach known as differential scanning calorimetry (DSC) has been applied and revealed a good agreement with the infrared and Raman spectroscopic results.