One-step microfluidics production of enzyme-loaded liposomes for the treatment of inflammatory diseases

Clarinda Costa, Zehua Liu, Sandra I. Simões, Alexandra Correia, Antti Rahikkala, Jani Seitsonen, Janne Ruokolainen, Ana Aguiar-Ricardo*, Hélder A. Santos, M. Luísa Corvo

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

The biopharmaceuticals market is constantly growing. Despite their advantages over the conventional drugs, biopharmaceuticals have short biological half-lifes, which can be increased using liposomes. However, the common bulk methods to produce biopharmaceuticals-loaded liposomes result in lost of encapsulation efficiency (E.E.), resulting in an expensive process. Herein, the encapsulation of a therapeutic enzyme in liposomes is proposed, using a glass-capillary microfluidic technique. Cu,Zn- Superoxide dismutase (SOD) is successfully encapsulated into liposomes (SOD@Liposomes). SOD@Liposomes with a mean size of 135 ± 41 nm, a polydispersity index of 0.13 ± 0.01, an E.E. of 59 ± 6 % and an enzyme activity of 82 ± 3 % are obtained. in vivo experiments show, through an ear edema model, that SOD@Liposomes administered by the intravenous route enable an edema inhibition of 65 % ± 8 %, over the 20 % ± 13 % of SOD in its free form. The histopathological analyses show a higher inflammatory cell accumulation on the ear treated with SOD in its free form, than treated with SOD@Liposomes. Overall, this work highlights the potential of microfluidics for the production of enzyme-loaded liposomes with high encapsulation efficiency, with the intrinsic advantages of the low time-consuming and easily upscaling microfluidic assembly method.

Original languageEnglish
Article number111556
Number of pages8
JournalColloids and Surfaces B: Biointerfaces
Volume199
DOIs
Publication statusPublished - Mar 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • Cu
  • Inflammation
  • Liposomes
  • Microfluidics
  • ROS
  • Zn- superoxide dismutase

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