Volume 4, Issue 2 , Pages 155-166, June 2008
Liposomal delivery improves the growth-inhibitory and apoptotic activity of low doses of gemcitabine in multiple myeloma cancer cells
Abstract
Gemcitabine-loaded pegylated unilamellar liposomes (200 nm) were proposed for the treatment of multiple myeloma cancer disease. Physicochemical and technological parameters of liposomes were evaluated by using laser light scattering and gel permeation chromatography. The growth-inhibitory activity of gemcitabine-loaded liposomes compared to the free drug was assayed in vitro on U266 (autocrine, interleukin-6-independent) and INA-6 (IL-6-dependent) multiple myeloma cell lines. Liposomes noticeably improved the growth-inhibitory activity of gemcitabine in terms of both dose-dependent and incubation-time effects. Liposomal delivery of gemcitabine consistently and significantly increased induction of apoptosis and caused a complete inhibition of proliferation. Liposomes were able to interact with multiple myeloma cells as demonstrated by confocal laser scanning microscopy and hence to improve the intracellular gemcitabine delivery. Gemcitabine-loaded liposomes were much more effective in vitro than the free drug. This formulation may offer even more in vivo advantages both in terms of drug pharmacokinetic and biodistribution.
Key words: Gemcitabine, Multiple myeloma, Pegylated liposomes
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This paper was financially supported by an AIRC 2005 grant, MIUR grants (PRIN 2005 and PRIN 2006), and a Ministero della Salute – Regione Calabria (Dipartimento Tutela della Salute Politiche Sanitarie e Sociali) grant. Dr. Natalia Malara was supported by a FIRC fellowship.
PII: S1549-9634(08)00033-6
doi:10.1016/j.nano.2008.02.003
© 2008 Elsevier Inc. All rights reserved.
Volume 4, Issue 2 , Pages 155-166, June 2008
