Tailoring structural properties of spray-dried methotrexate-loaded poly (lactic acid)/poloxamer microparticle blends

  • Edilene Gadelha de Oliveira
  • Paula Renata Lima Machado
  • Kleber Juvenal Silva Farias
  • Tiago R. da Costa
  • Dulce Maria Araújo Melo
  • Ariane Ferreira Lacerda
  • Matheus de Freitas Fernandes-Pedrosa
  • Alianda Maira Cornélio
  • Arnóbio Antônio da Silva-JuniorEmail author
Biomaterials Synthesis and Characterization Original Research
Part of the following topical collections:
  1. Biomaterials Synthesis and Characterization


Drug delivery systems can overcome cancer drug resistance, improving the efficacy of chemotherapy agents. Poly (lactic acid) (PLA) microparticles are an interesting alternative because their hydrophobic surface and small particle size could facilitate interactions with cells. In this study, two poloxamers (PLX 407 and 188) were applied to modulate the structural features, the drug release behavior and the cell viability from spray-dried microparticles. Five formulations with different PLA: PLX blend ratio (100:0, 75:25, 50:50, 25:50, and 0:100) were well-characterized by SEM, particle size analysis, FTIR spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction analysis (XRD). The spray-dried microparticles showed higher drug loading, spherical-shape, and smaller particle size. The type of poloxamer and blend ratio affected their structural and functional properties such as morphology, crystallinity, blend miscibility, drug release rate, and cell viability. The methotrexate (MTX), a model drug, was loaded in amorphous spray-dried microparticles. Moreover, the drug release studies demonstrated that PLX induced a leaching-effect of MTX from PLA: PLX blends, suggesting the formation of MTX/PLX micelles in aqueous medium. This finding was better established by cell viability assays. Therefore, biocompatible PLA: PLX blends showed promising in vitro results, and further in vivo studies will be performed to evaluate the performance of this chemotherapeutic agent.





Poly (lactic acid)

PLX 407

Poloxamer 407

PLX 188

Poloxamer 188


Poly (ethylene oxide)


Poly (propylene oxide) (PPO)

Blank PLA

Blank PLA microparticles

Blank PLX

Blank PLX microparticles


Methotrexate-loaded PLA microparticles


Methotrexate-loaded PLX microparticles


Blends between PLA and PLX

PLA: PLX 25:75

Blends between PLA and PLX in the ratio 25:75

PLA: PLX 50:50

Blends between PLA and PLX in the ratio 50:50

PLA: PLX 75:25

Blends between PLA and PLX in the ratio 75:25


Methotrexate-loaded PLA: PLX blends


Scanning Electron Microscopy


Polydispersity index


Drug loading


Encapsulation Efficiency


Dynamic Light Scattering


X-ray Diffraction Analysis


Differential Scanning Calorimetry


3-[4,5-dimethylthiazol-2-yl]−2,5-diphenyltetrazolium bromide


Fourier Transform Infrared Spectroscopy



The authors gratefully acknowledge the financial support from CNPQ (grant number: 479195/2008; 483073/2010-5, 481767/2012-6) and CAPES (Scholarship of E.G. Oliveira). The authors also thank the help of Andy Cumming in checking the English text.

Author contributions

E.G. Oliveira performed all experiments and drafted the manuscript. P.R.L. Machado and K.J.S. Farias were responsible for the cell assays. D.M.A. Melo, T.R. da Costa performed DSC analyses. M.F. Fernandes-Pedrosa and A.F. Lacerda suggested improvements in the experimental methodology and revised this part of the paper. A.M. Cornélio helped with discussion about biological activity. A.A. da Silva-Junior suggested the research line as well as wrote and revised the final version of the manuscript before submission.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Edilene Gadelha de Oliveira
    • 1
  • Paula Renata Lima Machado
    • 2
  • Kleber Juvenal Silva Farias
    • 2
  • Tiago R. da Costa
    • 3
  • Dulce Maria Araújo Melo
    • 3
  • Ariane Ferreira Lacerda
    • 1
  • Matheus de Freitas Fernandes-Pedrosa
    • 1
  • Alianda Maira Cornélio
    • 4
  • Arnóbio Antônio da Silva-Junior
    • 1
    Email author
  1. 1.Laboratory of Pharmaceutical Technology and Biotechnology, Department of PharmacyFederal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de FariasNatalBrazil
  2. 2.Department of Clinical AnalysisFederal University of Rio Grande do Norte, UFRN, Av. Gal. Gustavo Cordeiro de Farias s/n, PetropolisNatalBrazil
  3. 3.Institute of ChemistryFederal University of Rio Grande do Norte, UFRNNatalBrazil
  4. 4.Department of MorphologyFederal University of Rio Grande do Norte, UFRNNatalBrazil

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