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

  • Biomaterials Synthesis and Characterization
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

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.

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Abbreviations

MTX:

Methotrexate

PLA:

Poly (lactic acid)

PLX 407:

Poloxamer 407

PLX 188:

Poloxamer 188

PEO:

Poly (ethylene oxide)

PPO:

Poly (propylene oxide) (PPO)

Blank PLA:

Blank PLA microparticles

Blank PLX:

Blank PLX microparticles

MTX-PLA:

Methotrexate-loaded PLA microparticles

MTX-PLX:

Methotrexate-loaded PLX microparticles

PLA: PLX:

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

MTX-PLA: PLX:

Methotrexate-loaded PLA: PLX blends

SEM:

Scanning Electron Microscopy

SPAN:

Polydispersity index

DL:

Drug loading

EE:

Encapsulation Efficiency

DLS:

Dynamic Light Scattering

XRD:

X-ray Diffraction Analysis

DSC:

Differential Scanning Calorimetry

MTT:

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

FTIR:

Fourier Transform Infrared Spectroscopy

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Acknowledgements

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.

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, UFRN, Gal. Gustavo Cordeiro de Farias, Petrópolis, 59072-570, Natal, RN, Brazil

    Edilene Gadelha de Oliveira, Ariane Ferreira Lacerda, Matheus de Freitas Fernandes-Pedrosa & Arnóbio Antônio da Silva-Junior

  2. Department of Clinical Analysis, Federal University of Rio Grande do Norte, UFRN, Av. Gal. Gustavo Cordeiro de Farias s/n, Petropolis, 59012-570, Natal, RN, Brazil

    Paula Renata Lima Machado & Kleber Juvenal Silva Farias

  3. Institute of Chemistry, Federal University of Rio Grande do Norte, UFRN, Lagoa Nova, 59072-970, Natal, RN, Brazil

    Tiago R. da Costa & Dulce Maria Araújo Melo

  4. Department of Morphology, Federal University of Rio Grande do Norte, UFRN, Lagoa Nova, 59072-970, Natal, RN, Brazil

    Alianda Maira Cornélio

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  1. Edilene Gadelha de Oliveira
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  2. Paula Renata Lima Machado
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  3. Kleber Juvenal Silva Farias
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Correspondence to Arnóbio Antônio da Silva-Junior.

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de Oliveira, E.G., Machado, P.R.L., Farias, K.J.S. et al. Tailoring structural properties of spray-dried methotrexate-loaded poly (lactic acid)/poloxamer microparticle blends. J Mater Sci: Mater Med 30, 12 (2019). https://doi.org/10.1007/s10856-018-6214-6

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