Enhanced antiproliferative activity of the new anticancer candidate LPSF/AC04 in cyclodextrin inclusion complexes encapsulated into liposomes.
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-β-cyclodextrin (HP-β-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-β-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.
Laboratório de Síntese e Vetorização de Moléculas, Universidade Estadual da Paraíba, João Pessoa, PB, Brazil.
Elisângela A M
EA
Mendonça
Mariane C B
MC
Lira
Marcelo M
MM
Rabello
Isabella M F
IM
Cavalcanti
Suely L
SL
Galdino
Ivan R
IR
Pitta
Maria do Carmo A
Mdo C
Lima
Maira G R
MG
Pitta
Marcelo Z
MZ
Hernandes
Nereide S
NS
Santos-Magalhães
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000042:Absorption; D000166:Acridines / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D012995:Solubility; D045162:Thiazolidinediones / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
C568945:5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione; D000166:Acridines; D000970:Antineoplastic Agents; D005079:Excipients; D008081:Liposomes; D045162:Thiazolidinediones; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin