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Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation.

Authors :
Serna, Naroa
López-Laguna, Hèctor
Aceituno, Patricia
Rojas-Peña, Mauricio
Parladé, Eloi
Voltà-Durán, Eric
Martínez-Torró, Carlos
Sánchez, Julieta M.
Di Somma, Angela
Carratalá, Jose Vicente
Livieri, Andrea L.
Ferrer-Miralles, Neus
Vázquez, Esther
Unzueta, Ugutz
Roher, Nerea
Villaverde, Antonio
Source :
Pharmaceutics; Nov2023, Vol. 15 Issue 11, p2632, 14p
Publication Year :
2023

Abstract

Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19994923
Volume :
15
Issue :
11
Database :
Complementary Index
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
173868818
Full Text :
https://doi.org/10.3390/pharmaceutics15112632