Enhanced antiproliferative activity of the new anticancer candidate LPSF/AC04 in cyclodextrin inclusion complexes encapsulated into liposomes.
AAPS PharmSciTech
; 13(4): 1355-66, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23054982
ABSTRACT
LPSF/AC04 (5Z)-[5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione] is an acridine-based derivative, part of a series of new anticancer agents synthesized for the purpose of developing more effective and less toxic anticancer drugs. However, the use of LPSF/AC04 is limited due to its low solubility in aqueous solutions. To overcome this problem, we investigated the interaction of LPSF/AC04 with hydroxypropyl-ß-cyclodextrin (HP-ß-CyD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) in inclusion complexes and determine which of the complexes formed presents the most significant interactions. In this paper, we report the physical characterization of the LPSF/AC04-HP-CyD inclusion complexes by thermogravimetric analysis, differential scanning calorimetry, infrared spectroscopy absorption, Raman spectroscopy, (1)HNMR, scanning electron microscopy, and by molecular modeling approaches. In addition, we verified that HP-ß-CyD complexation enhances the aqueous solubility of LPSF/AC04, and a significant increase in the antiproliferative activity of LPSF/AC04 against cell lines can be achieved by the encapsulation into liposomes. These findings showed that the nanoencapsulation of LPSF/AC04 and LPSF/AC04-HP-CyD inclusion complexes in liposomes leads to improved drug penetration into the cells and, as a result, an enhancement of cytotoxic activity. Further in vivo studies comparing free and encapsulated LPSF/AC04 will be undertaken to support this investigation.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acridinas
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Tiazolidinedionas
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Beta-Ciclodextrinas
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Gama-Ciclodextrinas
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Lipossomos
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Antineoplásicos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article