AAPS PharmSciTech

, 20:165 | Cite as

Poly (ɛ-Caprolactone) Nanoparticles with pH-Responsive Behavior Improved the In Vitro Antitumor Activity of Methotrexate

  • Letícia Bueno Macedo
  • Daniele Rubert Nogueira-Librelotto
  • Josiele de Vargas
  • Laís Engroff Scheeren
  • María Pilar Vinardell
  • Clarice Madalena Bueno RolimEmail author
Research Article


A promising approach to achieve a more efficient antitumor therapy is the conjugation of the active molecule to a nanostructured delivery system. Therefore, the main objective of this research was to prepare nanoparticles (NPs), with the polymer poly (ε-caprolactone) (PCL), as a carrier for the antitumor drug methotrexate (MTX). A pH-responsive behavior was obtained through conjugation of the amino acid-based amphiphile, 77KL, to the NP matrix. The NPs showed mean hydrodynamic diameter and drug entrapment efficiency of 178.5 nm and 20.52%, respectively. Owing to its pH-sensitivity, the PCL-NPs showed membrane-lytic behavior upon reducing the pH value of surrounding media to 5.4, which is characteristic of the endosomal compartments. The in vitro antitumor assays demonstrated that MTX-loaded PCL-NPs have higher antiproliferative activity than free drug in MCF-7 cells and, to a lesser extent, in HepG2 cells. This same behavior was also achieved at mildly acidic conditions, characteristic of the tumor microenvironment. Altogether, the results evidenced the pH-responsive properties of the designed NPs, as well as the higher in vitro cytotoxicity compared to free MTX, representing thus a promising alternative for the antitumor therapy.


pH-responsive nanoparticles poloxamer lysine-based surfactant in vitro cell models cancer 


Funding Information

This research was supported by Grants 447548/2014-0 and 401069/2014-1 of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - Brazil) and 2293-2551/14-0 of Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS - Brazil). Letícia B. Macedo and Daniele R. Nogueira-Librelotto acknowledge Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES - Brazil) and CNPq - Brazil for the Master’s and Postdoctoral fellowships, respectively.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Letícia Bueno Macedo
    • 1
    • 2
  • Daniele Rubert Nogueira-Librelotto
    • 1
    • 2
  • Josiele de Vargas
    • 1
  • Laís Engroff Scheeren
    • 1
    • 2
  • María Pilar Vinardell
    • 3
  • Clarice Madalena Bueno Rolim
    • 1
    • 2
    Email author
  1. 1.Department of Industrial PharmacyUniversidade Federal de Santa MariaSanta MariaBrazil
  2. 2.PostGraduate Program in Pharmaceutical SciencesUniversidade Federal de Santa MariaSanta MariaBrazil
  3. 3.Department of Biochemistry and Physiology, Faculty of Pharmacy and Food ScienceUniversitat de BarcelonaBarcelonaSpain

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