title: 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 (approximately 10% apoptosis for PSL or Ab-PSL formulation vs. approximately 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.
authors.affiliation: Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: In-Ah
authors.initials: IA
authors.lastname: Lee
authors.forename: In-Young
authors.initials: IY
authors.lastname: Kim
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lim
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Cho
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D014410:Tumor Stem Cell Assay; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008055:Lipids; D008081:Liposomes; D003841:Deoxycytidine; C512478:EGFR protein, human; D066246:ErbB Receptors; C007740:fluorexon; D000093542:Gemcitabine