title: Oil-encapsulating PEO-PPO-PEO/PEG shell cross-linked nanocapsules for target-specific delivery of paclitaxel.
abstract: PEO-PPO-PEO/PEG shell cross-linked nanocapsules encapsulating an oil phase in their nanoreservoir structure was developed as a target-specific carrier for a water-insoluble drug, paclitaxel. Oil-encapsulating PEO-PPO-PEO/PEG composite nanocapsules were synthesized by dissolving an oil (Lipiodol) and an amine-reactive PEO-PPO-PEO derivative in dichloromethane and subsequently dispersing in an aqueous solution containing amine-functionalized six-arm-branched poly(ethylene glycol) by ultrasonication. The resultant shell cross-linked nanocapsules had a unique core/shell architecture with an average size of 110.7 +/- 9.9 nm at 37 degrees C, as determined by dynamic light scattering and transmission electron microscopy. Paclitaxel could be effectively solubilized in the inner Lipiodol phase surrounded by a cross-linked PEO-PPO-PEO/PEG shell layer. The paclitaxel-loaded nanocapsules were further conjugated with folic acid to achieve folate receptor targeted delivery. Confocal microscopy and flow cytometric analysis revealed that folate-mediated targeting significantly enhanced the cellular uptake and apoptotic effect against folate receptor overexpressing cancer cells. The present study suggested that these novel nanomaterials encapsulating an oil reservoir could be potentially applied for cancer cell targeted delivery of various water-insoluble therapeutic and diagnostic agents.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Bae
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Lee
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D007459:Iodized Oil; D053769:Nanocapsules / Q000737:chemistry*; D009821:Oils; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011409:Propylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012995:Solubility
chemical_list: D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D058973:Folate Receptors, GPI-Anchored; D053769:Nanocapsules; D009821:Oils; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D007459:Iodized Oil; D005492:Folic Acid; D017239:Paclitaxel