Secondary ions mass spectrometric method for assessing surface density of pegylated liposomal nanomedicines

Liposomal drug delivery relies on polyethylene glycol (PEG) coating since it is essential for preserving the stability and increasing the plasma half-life of the lipid-based nanocarriers, and therefore it represents a critical quality attribute of nanomedicine formulations. Due to the complexity of their therapeutic action and the implications if they prove to be ineffective, decision-making in nanomedicine development requires statistically meaningful correlations between design principles and their biophysical properties. Precise characterization of PEG functional coatings is essential for quality control of PEGylated liposomes, it is required not only to measure the total amount of nanoparticle incorporated PEG-chains but also their abundance and conformation at the nanoparticle external surface. In this study, we developed a methodology to characterize PEG-coatings of PEGylated liposomes using a cryogenic protocol for time-of-flight secondary ions mass spectrometry (ToF-SIMS). The method was applied to liposomes formulated with varying PEG-lipid contents in the formulation and the measurements successfully distinguished PEGylated liposomes based on their PEG-lipid content in the liposome outer membranes. ... mehrThese results indicate that the cryogenic ToF-SIMS method could be potentially used to control the quality of PEGylated liposomes not only for research and but also for drug manufacturing processes.