Anchoring Property of a Novel Hydrophilic Lipopolymer, HDAS-SHP, Post-Inserted in Preformed Liposomes

Polyethylene glycol (PEG)-phospholipids in long-circulating liposomes cause non-specific immune reactions; mainly attributable to negatively-charged phosphoryl s at the interface of PEG and phospholipid. We investigated a novel lipopolymer, by which a superhydrophilic polymer (SHP) is conjugated to a non-phospholipid N¹-(2-aminoethyl)-N⁴-hexadecyl-2-tetradecylsuccinamide (HDAS). The modification of preformed liposomes HDAS-SHP, HDAS-PEG₂₀₀₀, and DSPE-PEG₂₀₀₀ were performed by post-insertion techniques. The efficiency of post-insertion and desorption rates, from the liposome surface, were determined. HDAS-SHP micelles showed highly positive zeta potential (+28.4 mV); zeta potentials of DSPE-PEG₂₀₀₀ and HDAS-PEG₂₀₀₀ micelles were -34.4 mV, and -3.7 mV, respectively. Critical micelle concentration predicted amphiphilicity of HDAS-SHP (CMC 2.58 µM) as close to that of DSPE-PEG₂₀₀₀ (CMC 2.44 µM). Both HDAS-SHP and HDAS-PEG₂₀₀₀ post-inserted with comparable efficiency (79%, and 73%, respectively), but noticeably lower than DSPE-PEG₂₀₀₀ (90%). The desorption rate of HDAS-SHP was close to that of DSPE-PEG₂₀₀₀ (0.53%/h, and 0.45%/h, respectively); the desorption rate for HDAS-PEG₂₀₀₀ was slightly more at 0.67%/h. Compared to plain liposomes, both HDAS-SHP- and DSPE-PEG₂₀₀₀-liposomes showed significant leakage of encapsulated Na-fluorescein isothiocyanate (FITC) upon incubation with serum. At the same time, both modified liposomes were found to suppress serum levels of the complement proteins, Bb and C4d. We infer that HDAS-SHP is a viable alternative to commonly-used PEG-phospholipid derivatives for stealth purposes.