Fabrication of liposomal doxorubicin exhibiting ultrasensitivity against phospholipase A2 for efficient pulmonary drug delivery to lung cancers

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 10 min in the presence of 120 mU of PLA2 at 37 °C in vitro, whereas several other liposomal compositions used for inhalation therapy did not. DPPC/P188 liposomes were stable in the absence of PLA2 at 37 °C after 60 min incubation and drug release by PLA2 was 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 PLA2 concentrations 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 PLA2 exhibited 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.

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