title: Effective Remote Loading of Doxorubicin into DPPC/Poloxamer 188 Hybrid Liposome to Retain Thermosensitive Property and the Assessment of Carrier-Based Acute Cytotoxicity for Pulmonary Administration.
abstract: Functional liposome administration via the pulmonary route is of interest to treat pulmonary diseases, including cancer. Here, a block copolymer used as a medical additive, Poloxamer 188 (P188), was incorporated into liposome membranes, and the thermosensitive characteristics of the DPPC/P188 hybrid liposomes were assessed. An increase in P188 incorporation in DPPC liposomes enhanced the release of calcein, a fluorescence marker, from liposomes at 42°C in vitro; calcein release was significantly slower at 37°C. The lipid composition was optimal at a DPPC/P188 ratio of 3:0.4 (molar ratio). DPPC/P188 liposomes did not exhibit in vitro cytotoxicity against A549 cells and Raw 264.7 cells used as models of pulmonary cells or trigger in vivo acute inflammation as determined by the secretion of tumor necrosis factor alpha. Next, an anticancer drug, doxorubicin (DOX), was loaded with approximately 90% efficiency into DPPC/P188 liposomes using a remote-loading method and a DOX-phospholipid ratio of 1:20 (w/w). The interior buffer of liposome has remarkably changed DOX release at 42°C. DOX released from DPPC/P188 liposomes at 42°C exhibited cytotoxic effects toward A549 cells comparable with free DOX solution. These results suggest that a DOX-loaded DPPC/P188 liposome formulation administered via the pulmonary route may be useful for treating lung cancer.
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tagami
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kubota
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan. Electronic address: ozekit@phar.nagoya-cu.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; C506643:liposomal doxorubicin; D020442:Poloxamer; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Cancer chemotherapy; Controlled release/delivery; Encapsulation; Liposomes; Pulmonary drug delivery; Responsive delivery systems