2. Academic Validation
  3. Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia

Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia

  • Pharmacol Res. 2016 Sep:111:102-112. doi: 10.1016/j.phrs.2016.05.032.
Joyce C de Mello 1,  Vivian Wr Moraes 1,  Carolina M Watashi 1,  Deyse C da Silva 1,  Leide P Cavalcanti 2,  Margareth Kkd Franco 3,  Fabiano Yokaichiya 4,  Daniele R de Araujo 1,  Tiago Rodrigues 5
Affiliations

Affiliations

  • 1 Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil.
  • 2 Faculdade de Engenharia Quimica, Universidade de Campinas (Unicamp), Campinas, SP, Brazil.
  • 3 Instituto de Pesquisas Energéticas e Nucleares (IPEN), São Paulo, SP, Brazil.
  • 4 Department Quantum Phenomena in Novel Materials, Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Hahn-Meitner-Platz 1, Berlin, Germany.
  • 5 Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil. Electronic address: [email protected].
PMID: 27265114 DOI: 10.1016/j.phrs.2016.05.032
Abstract

The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics(®)) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in Cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in Cancer therapy.

Keywords

Cancer therapy; Leukemia; Multidrug resistance; Nanostructured systems; Phenothiazines; Poloxamers.

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