Polymeric Micelles Based on Hyaluronic Acid and Phospholipids: Design, Characterization, and Cytotoxicity

摘要

Novel amphiphilic copolymers were synthesized and characterized by ~1H NMR using Hyaluronic acid (HA) as a hydrophilic part and phosphatidylethanolamine (PE) including 1,2-dimiristoyl-sn-glycerol-3-phosphatidylethanolamine (DMPE) and 1,2-distearoyl-sn-glycerol-3-phosphatidylethanolamine (DSPE) as a hydrophobic segment. The newly developed HA-PE copolymers form a micelle in an aqueous media. The micellar properties, including critical micelle concentration (CMC) with pyrene as a fluorescence probe and micelle morphology, using transmission electron microscopy were assessed. It was found that the CMC values for HADMPE and HA-DSPE were 15.5 and 13.4 lg/mL, respectively. Also micelles were spherical in shape and within the size range of 162–214 nm. The solubility of cholesterol, a highly hydrophobic compound, was enhanced to 0.25 mg/mL which is much higher than it is in water (0.0001 mg/mL). In vitro cytotoxicity assay of HA-PE copolymers showed no toxicity on human breast cancer cell line (MCF-7). These results suggest that HA-PE micelles could be considered as a promising carrier for delivery of hydrophobic compounds.