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In vivo evaluation of pH-sensitive polymer-based immunoliposomes targeting the CD33 antigen.
Mol Pharm. 2010 May 17;
Authors: Simard P, Leroux JC
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-beta-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, non-targeted 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 non-targeted 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.
PMID: 20476756 [PubMed - as supplied by publisher]
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