Passive Diffusion vs Active pH-Dependent Encapsulation of
Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into
Folate-Targeted Ferritin Delivery System

J 2021

Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System

SKUBALOVA, Z., S. REX, M. SUKUPOVA, M. ZAHALKA, Petr SKLÁDAL et. al.

Basic information

Original name

Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System

Authors

SKUBALOVA, Z., S. REX, M. SUKUPOVA, M. ZAHALKA, Petr SKLÁDAL (203 Czech Republic, guarantor, belonging to the institution), Jan PŘIBYL (203 Czech Republic, belonging to the institution), H. MICHALKOVA, A. WEERASEKERA, V. ADAM and Z. HEGER

Edition

International Journal of Nanomedicine, Albany, New Zealnad, Dove Medical PRESS LTD, 2021, 1178-2013

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

New Zealand

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.033

RIV identification code

RIV/00216224:14740/21:00124270

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.2147/IJN.S275808

UT WoS

000607548900001

Keywords in English

drug delivery; nanomedicine; lenvatinib; vandetanib

Abstract

V originále

Introduction: The present study reports on examination of the effects of encapsulating the tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib into a biomacromolecular ferritin-based delivery system. Methods: The encapsulation of TKIs was performed via two strategies: i) using an active reversible pH-dependent reassembly of ferritin's quaternary structure and ii) passive loading of hydrophobic TKIs through the hydrophobic channels at the junctions of ferritin subunits. After encapsulation, ferritins were surface-functionalized with folic acid promoting active-targeting capabilities. Results: The physico-chemical and nanomechanical analyses revealed that despite the comparable encapsulation efficiencies of both protocols, the active loading affects stability and rigidity of ferritins, plausibly due to their imperfect reassembly. Biological experiments with hormone-responsive breast cancer cells (T47-D and MCF-7) confirmed the cytotoxicity of encapsulated and folate-targeted TKIs to folate-receptor positive cancer cells, but only limited cytotoxic effects to healthy breast epithelium. Importantly, the long-term cytotoxic experiments revealed that compared to the pH-dependent encapsulation, the passively-loaded TKIs exert markedly higher anticancer activity, most likely due to undesired influence of harsh acidic environment used for the pH-dependent encapsulation on the TKIs' structural and functional properties. Conclusion: Since the passive loading does not require a reassembly step for which acids are needed, the presented investigation serves as a solid basis for future studies focused on encapsulation of small hydrophobic molecules.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

SKUBALOVA, Z., S. REX, M. SUKUPOVA, M. ZAHALKA, Petr SKLÁDAL, Jan PŘIBYL, H. MICHALKOVA, A. WEERASEKERA, V. ADAM and Z. HEGER. Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System. International Journal of Nanomedicine. Albany, New Zealnad: Dove Medical PRESS LTD, 2021, vol. 16, No 2021, p. 1-14. ISSN 1178-2013. Available from: https://dx.doi.org/10.2147/IJN.S275808.

@article{1836579,
   author = {Skubalova, Z. and Rex, S. and Sukupova, M. and Zahalka, M. and Skládal, Petr and Přibyl, Jan and Michalkova, H. and Weerasekera, A. and Adam, V. and Heger, Z.},
   article_location = {Albany, New Zealnad},
   article_number = {2021},
   doi = {http://dx.doi.org/10.2147/IJN.S275808},
   keywords = {drug delivery; nanomedicine; lenvatinib; vandetanib},
   language = {eng},
   issn = {1178-2013},
   journal = {International Journal of Nanomedicine},
   title = {Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System},
   url = {https://www.dovepress.com/passive-diffusion-vs-active-ph-dependent-encapsulation-of-tyrosine-kin-peer-reviewed-fulltext-article-IJN},
   volume = {16},
   year = {2021}
}

TY  - JOUR
ID  - 1836579
AU  - Skubalova, Z. - Rex, S. - Sukupova, M. - Zahalka, M. - Skládal, Petr - Přibyl, Jan - Michalkova, H. - Weerasekera, A. - Adam, V. - Heger, Z.
PY  - 2021
TI  - Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System
JF  - International Journal of Nanomedicine
VL  - 16
IS  - 2021
SP  - 1-14
EP  - 1-14
PB  - Dove Medical PRESS LTD
SN  - 11782013
KW  - drug delivery
KW  - nanomedicine
KW  - lenvatinib
KW  - vandetanib
UR  - https://www.dovepress.com/passive-diffusion-vs-active-ph-dependent-encapsulation-of-tyrosine-kin-peer-reviewed-fulltext-article-IJN
N2  - Introduction: The present study reports on examination of the effects of encapsulating the tyrosine kinase inhibitors (TKIs) vandetanib and lenvatinib into a biomacromolecular ferritin-based delivery system. Methods: The encapsulation of TKIs was performed via two strategies: i) using an active reversible pH-dependent reassembly of ferritin's quaternary structure and ii) passive loading of hydrophobic TKIs through the hydrophobic channels at the junctions of ferritin subunits. After encapsulation, ferritins were surface-functionalized with folic acid promoting active-targeting capabilities. Results: The physico-chemical and nanomechanical analyses revealed that despite the comparable encapsulation efficiencies of both protocols, the active loading affects stability and rigidity of ferritins, plausibly due to their imperfect reassembly. Biological experiments with hormone-responsive breast cancer cells (T47-D and MCF-7) confirmed the cytotoxicity of encapsulated and folate-targeted TKIs to folate-receptor positive cancer cells, but only limited cytotoxic effects to healthy breast epithelium. Importantly, the long-term cytotoxic experiments revealed that compared to the pH-dependent encapsulation, the passively-loaded TKIs exert markedly higher anticancer activity, most likely due to undesired influence of harsh acidic environment used for the pH-dependent encapsulation on the TKIs' structural and functional properties. Conclusion: Since the passive loading does not require a reassembly step for which acids are needed, the presented investigation serves as a solid basis for future studies focused on encapsulation of small hydrophobic molecules.
ER  -

SKUBALOVA, Z., S. REX, M. SUKUPOVA, M. ZAHALKA, Petr SKLÁDAL, Jan PŘIBYL, H. MICHALKOVA, A. WEERASEKERA, V. ADAM and Z. HEGER. Passive Diffusion vs Active pH-Dependent Encapsulation of Tyrosine Kinase Inhibitors Vandetanib and Lenvatinib into Folate-Targeted Ferritin Delivery System. \textit{International Journal of Nanomedicine}. Albany, New Zealnad: Dove Medical PRESS LTD, 2021, vol.~16, No~2021, p.~1-14. ISSN~1178-2013. Available from: https://dx.doi.org/10.2147/IJN.S275808.

Detailed Information on Publication Record