4.7 Article

Fluorinated ionic liquids for protein drug delivery systems: Investigating their impact on the structure and function of lysozyme

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 526, Issue 1-2, Pages 309-320

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2017.05.002

Keywords

Ionic liquids; Therapeutic proteins; Lysozyme; Drug delivery systems; Fluorinated surfactants

Funding

  1. FCT/MEC (Portugal) [SFRH/BD/100563/2014, PD/BD/128201/2016]
  2. Investigador FCT [IF/00656/2014, IF/00190/2014, IF/00210/2014]
  3. Associate Laboratory for Green Chemistry LAQV [FCT/MEC (UID/QUI/50006/2013)]
  4. ERDF under the PT2020 Partnership [POCI-01-0145-FEDER- 007265]
  5. iNOVA4Health Research Unit [LISBOA-01-0145-FEDER-007344]
  6. FEDER
  7. MostMicro unit [LISBOA-01-0145-FEDER-007660]
  8. FEDER funds through COMPETE2020 - (POCI)
  9. national funds through FCT
  10. [PTDC/QEQ-EPR/5841/2014]
  11. [PTDC/QEQ-FTT/3289/2014]
  12. [IF/00210/2014/CP1244/CT0003]
  13. [UID/Multi/04551/2013]
  14. Fundação para a Ciência e a Tecnologia [UID/Multi/04551/2013, PD/BD/128201/2016, SFRH/BD/100563/2014] Funding Source: FCT

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Since the approval of recombinant human insulin by FDA in 1982, more than 200 proteins are currently available for pharmaceutical use to treat a wide range of diseases. However, innovation is still required to develop effective approaches for drug delivery. Our aim is to investigate the potential use of fluorinated ionic liquids (FILs) as drug delivery systems (DDS) for therapeutic proteins. Some initial parameters need to be assessed before further studies can proceed. This work evaluates the impact of FILs on the stability, function, structure and aggregation state of lysozyme. Different techniques were used for this purpose, which included differential scanning fluorimetry (DSF), spectrophotometric assays, circular dichroism (CD), dynamic light scattering (DLS), and scanning and transmission electron microscopy (SEM/TEM). Ionic liquids composed of cholinium-, imidazolium- or pyridinium- derivatives were combined with different anions and analysed at different concentrations in aqueous solutions (below and above the critical aggregation concentration, CAC). The results herein presented show that the addition of ionic liquids had no significant effect on the stability and hydrolytic activity of lysozyme. Moreover, a distinct behaviour was observed in DLS experiments for non-surfactant and surfactant ionic liquids, with the latter encapsulating the protein at concentrations above the CAC. These results encourage us to further study ionic liquids as promising tools for DDS of protein drugs. (C) 2017 Elsevier B.V. All rights reserved.

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