In Vivo Evaluation of pH-Sensitive Polymer-Based Immunoliposomes Targeting the CD33 Antigen

The purpose of this study was to evaluate in vivo a targeted pH-sensitive liposomal formulation tailored to promote the efficient intracellular delivery of 1-β-d-arabinofuranosylcytosine (ara-C) to human myeloid leukemia cells. Specifically, pH-sensitive immunoliposomes were obtained by anchoring a copolymer of dioctadecyl, N-isopropylacrylamide and methacrylic acid in bilayers of PEGylated liposomes (LP) and by coupling the whole anti-CD33 monoclonal antibody (mAb) or its Fab′ fragments. Their pharmacokinetic and biodistribution profiles were assessed in Balb/c and leukemic HL60-bearing immunodepressed (SCID) mice. In naive mice, nontargeted and pH-sensitive Fab′-LP had longer circulation times than LP with whole mAb. In SCID/HL60 (CD33+) mice, the pharmacokinetic and biodistribution profiles of LP and encapsulated ara-C were comparable between nontargeted and pH-sensitive Fab′-LP. In leukemic mice, only pH-insensitive, ara-C-loaded Fab′ induced prolonged survival times. The apparent absence of pH-sensitive Fab′-LP effect could be related to lower exposure to ara-C in SCID mice.