title: Fabrication of liposomal doxorubicin exhibiting ultrasensitivity against phospholipase A2for efficient pulmonary drug delivery to lung cancers.
abstract: Phospholipase A2(PLA2) is expressed in inflammation-related tissue, including cancer tumors. We report that a hybrid liposome composed of phospholipid (DPPC) and PEGylated block-copolymer (Poloxamer 188) can rapidly release an encapsulated hydrophilic drug in the presence of PLA2. DPPC/P188 liposomes released approximately 80% of the encapsulated calcein (a fluorescence marker) within 10min in the presence of 120 mU of PLA2at 37°C in vitro, whereas several other liposomal compositions used for inhalation therapy did not. DPPC/P188 liposomes were stable in the absence of PLA2at 37°C after 60min incubation and drug release by PLA2was dependent on the amount of P188 incorporated into the DPPC liposomes. Drug release from doxorubicin (DOX, anticancer drug)-loaded DPPC/P188 liposomes was facilitated at higher PLA2concentrations and was dependent on the temperature and the presence of calcium ion, thus partially explaining PLA2-responsive drug release. DOX release from liposomes triggered by PLA2exhibited the same cytotoxic effects on the A549 lung cancer cell line as did DOX in free solution. These findings suggest that DPPC/P188 liposomes are a promising drug carrier for delivering drug efficiently at PLA2-expressing sites such as inflammatory lung cancer.
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, 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, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ando
authors.affiliation: Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, 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; D000072283:A549 Cells; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism*; D020442:Poloxamer / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D020442:Poloxamer; D015060:1,2-Dipalmitoylphosphatidylcholine; D004317:Doxorubicin; D054467:Phospholipases A2
keywords: Inhalation formulation; Liposome; Lung cancer; Phospholipase A(2); Poloxamer; Triggered release