title: In vitro and in vivo antitumor effects of folate-targeted ursolic acid stealth liposome.
abstract: The antitumor efficacy of ursolic acid (UA) was limited by poor hydrophilicity and low bioavailability. To overcome this issue, UA was encapsulated in liposomes modified with folate conjugates for better solubility and bioavailability. This novel agent was prepared by a thin-film dispersion method and characterized by mean diameter, zeta potential, and entrapment efficiency (160.1 nm, -21.2 mV, and 88.9%, respectively). In vitro, cellular uptake efficiency, cytotoxicity, apoptosis, and cell cycle analyses were performed to show that folate-receptor (FR) positive cells endocytose more FR-targeted liposome (FTL-UA) than nontargeted PEGylated liposome (PL-UA) and that FTL-UA induced more cytotoxicity and higher apoptosis than PL-UA. Pharmacokinetic assessments showed advantages of systemic bioavailability of FTL-UA (AUC = 218.32 mg/L·h, t1/2 = 7.61 h) over free UA (AUC = 36.88 mg/L·h, t1/2 = 0.78 h). In vivo, FTL-UA showed significantly higher human epidermoid carcinoma (KB) inhibition in Balb/c nu/nu mice compared to PL-UA or free UA. The results indicate the great potential of FTL-UA against KB tumor.
authors: Pharmacy School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors: Guang
authors: G
authors: Yang
authors: Tan
authors: T
authors: Yang
authors: Wendian
authors: W
authors: Zhang
authors: Miao
authors: M
authors: Lu
authors: Xiang
authors: X
authors: Ma
authors: Guangya
authors: G
authors: Xiang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019540:Area Under Curve; D001682:Biological Availability; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002788:Cholesterol Esters / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D009062:Mouth Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D014315:Triterpenes / Q000737:chemistry / Q000493:pharmacokinetics*; D023041:Xenograft Model Antitumor Assays; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002788:Cholesterol Esters; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid; D008081:Liposomes; D011092:Polyethylene Glycols; D014315:Triterpenes; D000097245:Ursolic Acid; C013440:cholesteryl succinate