Mass spectrometry study of ascorbyl palmitate as an agent for nanosomes formation

Abstract

Background. Study of properties and intermolecular interactions of biologically active compounds which can be used for the purposes of transmembrane drugs delivery is a topical task of modern molecular biophysics. Ascorbyl Palmitate (AP) as a fat-soluble form of vitamin C has recently attracted attention as a promising agent for formation of nanosomes for the “fat insoluble” drug molecules transfer through membranes. However, AP is not sufficiently characterized by up-to-date soft ionization mass spectrometric techniques. Objectives. The aim of the present work is to characterize AP and its intermolecular interactions by a number of mass spectrometric techniques: Electrospray Ionization (ESI), Laser Desorption/Ionization (LDI) and Matrix-Assisted Laser Desorption/Ionization (MALDI). The comparison of these techniques applicability to the study of AP intermolecular interactions as a drug delivery assisting agent is scheduled. Methods. ESI mass spectra are obtained with triple quadrupole Micromass Quattro mass spectrometer. LDI and MALDI experiments are performed by Autoflex II mass spectrometer. Results. In the ESI experiments in the positive ion mode abundant peaks of protonated and cationized AP molecules as well as the peaks of AP clusters nAP•H+ and nAP•Na+ (n=2÷4) are revealed in the mass spectra. This result testifies to the formation of stable noncovalent complexes of the AP molecules in the polar media and confirms the AP ability of formation nanosomes for drug delivery. Analysis of LDI and MALDI mass spectra of AP in positive and negative ion modes shows that in the presence of molecular ions of AP, the peaks of AP dimers or larger AP clusters are not recorded. The ESI probing of the model system containing AP and dipalmitoylphosphatidylcholine (DPPC) reveals stable AP•DPPC•H+ complex which models the AP intermolecular interactions with the phospholipid components of biomembranes and/or liposomes under AP functioning as a drug delivery assisting agent. Conclusions. The current study demonstrates the applicability of all tested mass spectrometric techniques for AP identification in solutions and solid phase, while for the purpose of examining of the AP noncovalent complexes formation and study of AP interactions with biomolecules the ESI is defined as the most effective technique.

Keywords

• ascorbyl palmitate
• nanosomes for drugs delivery
• dipalmitoylphosphatidylcholine
• noncovalent complexes
• mass spectrometry
• electrospray ionization
• laser desorption/ionization
• matrix-assisted laser desorption/ionization