[PMID]: | 27917871 |
[Au] Autor: | Zhu JJ; Zhang XX; Miao YQ; He SF; Tian DM; Yao XS; Tang JS; Gan Y |
[Ad] Endereço: | Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Ji-nan University, Guangzhou 510632, China. |
[Ti] Título: | Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells. |
[So] Source: | Acta Pharmacol Sin;38(2):290-300, 2017 Feb. |
[Is] ISSN: | 1745-7254 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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 (IC =2.94 µmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC values (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. |
[Mh] Termos MeSH primário: |
Glicosídeos Cardíacos/administração & dosagem Glicosídeos Cardíacos/farmacologia Portadores de Fármacos/química Micelas Poloxaleno/química
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[Mh] Termos MeSH secundário: |
Animais Glicosídeos Cardíacos/uso terapêutico Linhagem Celular Tumoral Quitosana/química Seres Humanos Camundongos Tamanho da Partícula Ensaios Antitumorais Modelo de Xenoenxerto
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Cardiac Glycosides); 0 (Drug Carriers); 0 (Micelles); 0 (acetylthevetin B); 0 (pluronic block copolymer P123); 9003-11-6 (Poloxalene); 9012-76-4 (Chitosan) |
[Em] Mês de entrada: | 1706 |
[Cu] Atualização por classe: | 170912 |
[Lr] Data última revisão:
| 170912 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 161206 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1038/aps.2016.113 |
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