Formulation of injectable glycyrrhizic acid-hydroxycamptothecin micelles as new generation of DNA topoisomerase I inhibitor for enhanced antitumor activity.
Int J Pharm
; 571: 118693, 2019 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-31525442
ABSTRACT
To develop a new drug delivery system is one of the useful approaches to break through the limitation of hydroxycamptothecin (HCPT), a typical DNA topoisomerase I (Topo I) inhibitor in clinical appliance. Injectable glycyrrhizic acid-hydroxycamptothecin (GL-HCPT) micelles that were able to dramatically improve the solubility and stability of HCPT were prepared through self-assembly process and evaluated both in vitro and in vivo. With a mean particle size (PS) of 105.7⯱â¯9.7â¯nm and a drug loading (DL) of 9.0⯱â¯1.5%, GL-HCPT micelles were rapidly internalized by HepG2 cells after 1â¯h, significantly increasing the intracellular accumulation of HCPT. Compared with the current used HCPT injection and HCPT/GL physical mixture, GL-HCPT micelles showed enhanced antitumor activity against liver cancer cells (HepG2 and Huh7) as well as a superior suppression on the tumor growth of HepG2 tumor bearing mice. Interestingly, GL-HCPT micelles gathered in liver and simultaneously reduced the drug accumulation in normal tissues, thereby exhibiting minimal cytotoxicity to human normal liver cells (LO2). Therefore, we offered a convenient and cost-effective strategy to construct an intravenous drug delivery system (GL-HCPT micelles) as new generation of DNA Topo I inhibitor for enhanced cancer chemotherapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
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Portadores de Fármacos
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Ácido Glicirrízico
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Inibidores da Topoisomerase I
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Neoplasias
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2019
Tipo de documento:
Article