Stealth nanocarriers based sterosomes using PEG post-insertion process

Sterosomes (STEs), a new and promising non-phospholipidic liposome platform based on palmitic acid (PA) and cholesterol (Chol) mixtures, need to have polyethylene glycol (PEG) chains grafted to their surface in order to obtain long-circulating nanocarriers in the blood stream. A post-insertion method was chosen to achieve this modification. The post-insertion process of PEG-modified distearoylphosphoethanolamine (DSPE-PEG) was monitored using the zeta potential value of STEs. Various conditions including PEG chain length and the DSPE-PEG/PA-Chol ratio, were explored. Zeta potential of STEs changed from about −40 mV for non-modified STEs to values close to 0 mV by the end of the process, i.e. for PEG-modified STEs. The kinetics of DSPE-PEG insertion and the stability of the resulting PEG-modified STEs were not considerably influenced, within the investigated range, by changes in PEG chain lengths and in DSPE-PEG/PA-Chol proportion. The post-insertion of PEG chains reduced in vitro complement activation as well as in vitro macrophage uptake compared to the non-modified STEs. Moreover, longer blood circulation time in mice was established for PEG-modified STEs intravenously injected compared to non-modified STEs. These results establish that post-insertion process of PEG chains to STEs is a promising strategy for developing long-term circulating drug delivery nanocarriers. Fil: Cieślak, Anna. University Of Angers; Francia Fil: Wauthoz, Nathalie. University Of Angers; Francia. Université Libre de Bruxelles; Bélgica Fil: Nieto Orellana, Alejandro. University Of Angers; Francia Fil: Lautram, Nolwenn. University Of Angers; Francia Fil: Béjaud, Jérôme. University Of Angers; Francia Fil: Hureaux, José. University Of Angers; Francia Fil: Lafleur, Michel. University of Montreal; Canadá Fil: Benoit, Jean-Pierre. University Of Angers; Francia Fil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Bastiat, Guillaume. University Of Angers; Francia