title: Vitamin E TPGS modified liposomes enhance cellular uptake and targeted delivery of luteolin: An in vivo/in vitro evaluation.
abstract: Luteolin (LUT) is an active agent in cancer prevention and a potential candidate for clinical chemotherapy. However, poor water solubility and extensive excretion have limited the clinical use of luteolin. Herein, we attempted to develop vitamin E d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS) coated liposomes to improve the accumulation of luteolin in lung cancer. Luteolin or coumarin-6 loaded liposomes were prepared using film-dispersion methods and characterized according to their particle size, polydispersity, zeta potential, and drug encapsulation efficiency. Cellular uptake properties and cytotoxicities of luteolin or coumarin-6 loaded liposomes were determined in A549 cells. Optical in vivo imaging was employed as a method of assessing tumor targeting. The antitumor effect was evaluated in mice xenotransplanted with A549 cancer cells. The results showed that TPGS coated liposomes are spherical, and are ∼176.2nm in size. TPGS coated liposomes enhanced cellular uptake and apoptosis by upregulating the Bax/Bcl-2 ratio, resulting in improved cytotoxicity in A549 cells. TPGS coated liposomes significantly accumulated in tumor tissue and enhanced tumor inhibition without altering the structures of other organs. Thereby, TPGS coated liposomes provide an effective strategy in cancer chemotherapy for model drugs with poor water solubility such as luteolin.
authors.affiliation: The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Jinli
authors.initials: J
authors.lastname: Li
authors.affiliation: Suzhou Integrated of Chinese and Western Medicine Hospital, Suzhou, People's Republic of China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Jiangsu Cancer Hospital, Nanjing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, People's Republic of China.
authors.forename: Weiming
authors.initials: W
authors.lastname: He
authors.affiliation: The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Ni
authors.affiliation: The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Peihua
authors.initials: P
authors.lastname: Xiong
authors.affiliation: The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China. Electronic address: weiminggang@suda.edu.cn.
authors.forename: Minggang
authors.initials: M
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D047311:Luteolin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D051379:Mice; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D003374:Coumarins; D004337:Drug Carriers; D008081:Liposomes; D013844:Thiazoles; C517282:coumarin 6; D011092:Polyethylene Glycols; D024502:alpha-Tocopherol; D047311:Luteolin
keywords: Liposomes; Lung cancer; Luteolin; TPGS