Enhanced Antiproliferative Activity of the New Anticancer Candidate LPSF/AC04 in Cyclodextrin Inclusion Complexes Encapsulated into Liposomes

被引：27

作者：

Mendonca, Elisangela A. M. ^{[2
,3
]}

Lira, Mariane C. B. ^{[1
,3
]}

Rabello, Marcelo M. ^{[4
]}

Cavalcanti, Isabella M. F. ^{[3
]}

Galdino, Suely L. ^{[5
]}

Pitta, Ivan R. ^{[5
]}

Lima, Maria do Carmo A. ^{[5
]}

Pitta, Maira G. R. ^{[6
]}

Hernandes, Marcelo Z.

Santos-Magalhaes, Nereide S. ^{[1
]}

机构：

[1] CAV, Recife, PE, Brazil

[2] Univ Estadual Paraiba UEPB, Lab Sintese & Vetorizacao Mol, Joao Pessoa, Paraiba, Brazil

[3] Univ Fed Pernambuco UFPE, LIKA, BR-50670901 Recife, PE, Brazil

[4] Lab Quim Teor Med UFPE, Recife, PE, Brazil

[5] Lab Planejamento & Sintese Farmacos UFPE, Recife, PE, Brazil

[6] Lab Imunomodulacao & Novas Abordagens Terapeut UF, Recife, PE, Brazil

来源：

AAPS PHARMSCITECH | 2012年 / 13卷 / 04期

关键词：

acridine; cyclodextrins; cytotoxicity; liposomes; modeling; BETA-CYCLODEXTRIN; ACRIDINE-DERIVATIVES; TOPOISOMERASE-II; X-RAY; PROLIFERATION; SOLUBILITY; STABILITY; DRUGS; STATE; DSC;

D O I：

10.1208/s12249-012-9853-9

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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-beta-cyclodextrin (HP-beta-CyD) and hydroxypropyl-gamma-cyclodextrin (HP-gamma-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, (HNMR)-H-1, scanning electron microscopy, and by molecular modeling approaches. In addition, we verified that HP-beta-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.

引用

页码：1355 / 1366

页数：12

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