TY - JOUR
T1 - One-step microfluidics production of enzyme-loaded liposomes for the treatment of inflammatory diseases
AU - Costa, Clarinda
AU - Liu, Zehua
AU - Simões, Sandra I.
AU - Correia, Alexandra
AU - Rahikkala, Antti
AU - Seitsonen, Jani
AU - Ruokolainen, Janne
AU - Aguiar-Ricardo, Ana
AU - Santos, Hélder A.
AU - Corvo, M. Luísa
N1 - Funding Information:
C. Costa and A. Aguiar-Ricardo are grateful for the financial support of the Associate Laboratory for Green Chemistry-LAQV, Faculdade de Ci?ncias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal, which is financed by national funds from FCT/MCTES (UIDB/50006/2020). C. Costa also acknowledges the FCT/MCTES for the grant PD/BD/142880/2018 and for the travel grant. M.L. Corvo acknowledges the financial support from Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal, which is supported in part by UID/DTP/04138/2020 from FCT/MCTES, Portugal. H.A. Santos acknowledges financial support from the HiLIFE Research Funds and Sigrid Jus?lius Foundation, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Funding Information:
C. Costa and A. Aguiar-Ricardo are grateful for the financial support of the Associate Laboratory for Green Chemistry-LAQV, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal , which is financed by national funds from FCT/MCTES ( UIDB/50006/2020 ). C. Costa also acknowledges the FCT/MCTES for the grant PD/BD/142880/2018 and for the travel grant. M.L. Corvo acknowledges the financial support from Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal , which is supported in part by UID/DTP/04138/2020 from FCT/MCTES, Portugal. H.A. Santos acknowledges financial support from the HiLIFE Research Funds and Sigrid Jusélius Foundation, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland .
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - Cu
KW - Inflammation
KW - Liposomes
KW - Microfluidics
KW - ROS
KW - Zn- superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=85099200802&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2020.111556
DO - 10.1016/j.colsurfb.2020.111556
M3 - Article
C2 - 33421927
AN - SCOPUS:85099200802
SN - 0927-7765
VL - 199
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
M1 - 111556
ER -