Preparation of pH-sensitive, long-circulating and EGFR-targeted immunoliposomes

Abstract

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 (∼10% apoptosis for PSL or Ab-PSL formulation vs. ∼1% 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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Correspondence to Jin-Seok Kim.

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Kim, MJ., Lee, H.J., Lee, IA. et al. Preparation of pH-sensitive, long-circulating and EGFR-targeted immunoliposomes. Arch. Pharm. Res. 31, 539 (2008). https://doi.org/10.1007/s12272-001-1190-9

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Key words

  • pH-Sensitive liposome (PSLs)
  • Gemcitabine
  • EGFR
  • NSCLC
  • Targeting