pH-Sensitive mPEG-Hz-Cholesterol Conjugates as a Liposome Delivery System

Hydrazone (Hz)-based pH-sensitive methoxy(polyethylene glycol)-cholesterol conjugates (mPEG-Hz-Chol), were synthesized and used to fabricate liposomes. The structures of the mPEG2000-Hz-Chol conjugate were confirmed by FT-IR and ¹ H-NMR; they were stable at pH 7.4 but sensitive to mild acid conditions (pH 5.5). Plain liposomes were also prepared with S100PC/ Chol, and the pH-insensitive liposomes with S100PC/Chol/mPEG2000-Chol for comparison; all the liposomes were similar in diameter ∼200 nm. In vitro, the pH-sensitive liposomes released more of the model drug, paclitaxel (PTX), than the plain liposomes. The pH-sensitive liposomes were less toxic than the plain liposomes and exhibited higher cellular uptake of PTX compared with pH-insensitive liposomes by human breast cancer cells (MCF-7). The pHsensitive mPEG2000-Hz-Chol liposomes are now being investigated as a potential new liposome drug delivery system.