pH-Responsive hyaluronated liposomes for docetaxel delivery

In this study, we report pH-responsive liposomes consisting of hydrogenated soy phosphatidylcholine (HSPC) as a lipid, hyaluronic acid (HA) grafted with functional 3-diethylaminopropyl (DEAP) groups (hereafter denoted as HA-g-DEAP) as a pH-responsive polymer, and docetaxel (DTX) as an antitumor drug. DTX-loaded HSPC liposomes were prepared via a conventional liposome manufacturing procedure and then were decorated with HA-gDEAP (HA-g-DEAP(0.15), HA-g-DEAP(0.25), and HA-g-DEAP(0.40), according to the molar conjugate ratio of DEAP to HA) in an aqueous solution (pH 7.4), by sonication. The liposomes with HA-g-DEAP(0.40) allowed the efficient release of the encapsulated DTX content when the pH of the solution decreased to 6.5 (Le., endosomal pH), owing to the acidic pH-induced protonation of the DEAP anchored to the vesicular lipid bilayers. These hyaluronated liposomes were effective at entering the human colon carcinoma HCT-116 cells with a CD44 receptor overexpression. In an in vitro tumor cell cytotoxicity test, the DTX-loaded liposomes caused a significant increase in HCT-116 tumor cell death, revealing their pharmaceutical potential in tumor therapy.