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

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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-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, 1HNMR, 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.

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Acknowledgments

The thermal analyses were performed at the Pharmaceutical Technology Laboratory of the UFPE Department of Pharmacy, with the kind collaboration of Dr. Pedro Rolim and the much appreciated technical assistance of Mrs. Larissa Rolim.

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Authors and Affiliations

  1. Laboratório de Síntese e Vetorização de Moléculas, Universidade Estadual da Paraíba (UEPB), João Pessoa, PB, Brazil

    Elisângela A. M. Mendonça

  2. Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Cidade Universitária, 50670-901, Recife, PE, Brazil

    Elisângela A. M. Mendonça, Mariane C. B. Lira & Isabella M. F. Cavalcanti

  3. Centro Acadêmico de Vitoria (CAV), Recife, PE, Brazil

    Mariane C. B. Lira & Nereide S. Santos-Magalhães

  4. Laboratório de Química Teórica Medicinal-UFPE, Recife, PE, Brazil

    Marcelo M. Rabello & Marcelo Z. Hernandes

  5. Laboratório de Planejamento e Síntese de Fármacos-UFPE, Recife, PE, Brazil

    Suely L. Galdino, Ivan R. Pitta & Maria do Carmo A. Lima

  6. Laboratório de Imunomodulação e Novas Abordagens Terapêuticas-UFPE, Recife, PE, Brazil

    Maira G. R. Pitta

Authors
  1. Elisângela A. M. Mendonça
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  2. Mariane C. B. Lira
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  3. Marcelo M. Rabello
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  4. Isabella M. F. Cavalcanti
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  5. Suely L. Galdino
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  6. Ivan R. Pitta
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  7. Maria do Carmo A. Lima
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  8. Maira G. R. Pitta
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  9. Marcelo Z. Hernandes
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  10. Nereide S. Santos-Magalhães
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Correspondence to Nereide S. Santos-Magalhães.

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Mendonça, E.A.M., Lira, M.C.B., Rabello, M.M. et al. Enhanced Antiproliferative Activity of the New Anticancer Candidate LPSF/AC04 in Cyclodextrin Inclusion Complexes Encapsulated into Liposomes. AAPS PharmSciTech 13, 1355–1366 (2012). https://doi.org/10.1208/s12249-012-9853-9

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  • DOI: https://doi.org/10.1208/s12249-012-9853-9

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