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KMID : 0043320080310040539
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Archives of Pharmacal Research
2008 Volume.31 No. 4 p.539 ~ p.546
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Preparation of pH-Sensitive, Long-Circulating and EGFR-Targeted Immunoliposomes
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Kim Min-Jung
Lee Hyo-Jung
Lee In-Ah
Kim In-Young
Lim Sun-Kyung
Cho Hyun-Ah
Kim Jin-Seok
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Abstract
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A long-circulating formulation of pH-sensitive liposomes (PSLs) with antibodies against epidermal growth factor receptor (EGFR) attached was designed, expecting an increase in binding and delivery of liposomes to the target cells including non-small cell lung cancer (NSCLC) cells. Physicochemical properties of the PSLs were measured by SEM and DLS. Leakage of a self-quenching fluorescent probe, calcein, from the liposome was studied for the evaluation of pH-sensitivity. Encapsulation efficiency of gemcitabine (an anti-cancer drug) in PSLs was about 67%. Average size of liposomes was 88 nm in diameter. The PSL of DOPE/CHEMS (6:4 molar ratio) formulation showed a dramatic pH-sensitivity at/around pH 5.5, whereas non-PSL of DPPC/Chol or PC/CHEMS formulation did not. Anti-proliferation effect of gemcitabine-encapsulating PSLs & Ab-PSLs in A549 cells was 2-fold higher than the free drug, which was further elucidated by the apoptosis of the cells by gemcitabine ( apoptosis for PSL or Ab-PSL formulation vs. for free drug or non-PSL formulation) using FACS analysis. These data demonstrate delivery of gemcitabine to tumor cells can be improved by long-circulating PSLs or Ab-PSLs formulations in vitro.
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KEYWORD
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pH-Sensitive liposome (PSLs), Gemcitabine, EGFR, NSCLC, Targeting
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