Tailoring structural properties of spray-dried methotrexate-loaded poly (lactic acid)/poloxamer microparticle blends
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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
- PLX 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
- 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
Scanning Electron Microscopy
Dynamic Light Scattering
X-ray Diffraction Analysis
Differential Scanning Calorimetry
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.
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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