Hyaluronic acid-coated liposomes for active targeting of gemcitabine.

摘要: The aim of this work was the preparation, characterization, and preliminary evaluation targeting ability toward pancreatic adenocarcinoma cells liposomes containing gemcitabine lipophilic prodrug [4-(N)-lauroyl-gemcitabine, C12GEM]. Hyaluronic acid (HA) selected as agent since it is biodegradable, biocompatible, can be chemically modified its cell surface receptor CD44 overexpressed on various tumors. For purpose, conjugates between a phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), HA two different low molecular weights 4800 Da (12 disaccharidic units) 12,000 (32 units), were prepared, characterized, introduced in during preparation. Different liposomal formulations prepared their characteristics analyzed: size, Z potential, TEM analyses underline difference HA-liposomes from non-HA ones. In order to better understand HA-liposome cellular localization evaluate interaction with receptor, confocal microscopy studies performed. results demonstrate that facilitates recognition by MiaPaCa2 (CD44(+)) uptake increases increase polymer weight. Finally, cytotoxicity preparations evaluated data show incorporation C12GEM cytotoxic activity inhibit growth more than plain liposomes. Altogether, specificity CD44-overexpressing line using ligand.