title: Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells.
abstract: Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40-50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects.
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Ji-nan University, Guangzhou 510632, China.|Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yun-Qiu
authors.initials: YQ
authors.lastname: Miao
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: He
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Ji-nan University, Guangzhou 510632, China.
authors.forename: Dan-Mei
authors.initials: DM
authors.lastname: Tian
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Ji-nan University, Guangzhou 510632, China.
authors.forename: Xin-Sheng
authors.initials: XS
authors.lastname: Yao
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Ji-nan University, Guangzhou 510632, China.|State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jin-Shan
authors.initials: JS
authors.lastname: Tang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gan
mesh_terms: D000818:Animals; D002301:Cardiac Glycosides / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008823:Micelles; D010316:Particle Size; D011060:Poloxalene / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002301:Cardiac Glycosides; D004337:Drug Carriers; D008823:Micelles; C000620890:acetylthevetin B; C464484:pluronic block copolymer P123; D011060:Poloxalene; D048271:Chitosan