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Aspherical and Spherical InvA497-Functionalized Nanocarriers for Intracellular Delivery of Anti-Infective Agents.

Castoldi, Arianna
; ; 
De Rossi, Chiara
; 
Mayr, Karsten
; ; 
Hartmann, Rolf
; ; 
Gordon, Sarah
; 
Lehr, Claus-Michael
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Issue Date
2018-12-05
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Abstract
The objective of this work was to evaluate the potential of polymeric spherical and aspherical invasive nanocarriers, loaded with antibiotic, to access and treat intracellular bacterial infections. Aspherical nanocarriers were prepared by stretching of spherical precursors, and both aspherical and spherical nanocarriers were surface-functionalized with the invasive protein InvA497. The relative uptake of nanocarriers into HEp-2 epithelial cells was then assessed. Nanocarriers were subsequently loaded with a preparation of the non-permeable antibiotic gentamicin, and tested for their ability to treat HEp-2 cells infected with the enteroinvasive bacterium Shigella flexneri. InvA497-functionalized nanocarriers of both spherical and aspherical shape showed a significantly improved rate and extent of uptake into HEp-2 cells in comparison to non-functionalized nanocarriers. Functionalized and antibiotic-loaded nanocarriers demonstrated a dose dependent killing of intracellular S. flexneri. A slight but significant enhancement of intracellular bacterial killing was also observed with aspherical as compared to spherical functionalized nanocarriers at the highest tested concentration. InvA497-functionalized, polymer-based nanocarriers were able to efficiently deliver a non-permeable antibiotic across host cell membranes to affect killing of intracellular bacteria. Functionalized nanocarriers with an aspherical shape showed an interesting future potential for intracellular infection therapy.
Citation
Pharm Res. 2018 Dec 5;36(1):22. doi: 10.1007/s11095-018-2521-3.
Affiliation
HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
Publisher
Springer
Journal
Pharmaceutical research
URI
http://hdl.handle.net/10033/621663
DOI
10.1007/s11095-018-2521-3
PubMed ID
30519925
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Article
Language
en
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ISSN
1573-904X
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Attribution-NonCommercial-ShareAlike 4.0 International
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publications of the research group drug delivery ([HIPS] DDEL)
publications of the research group drug design and optimization(HIPS]DDOP)
publications of the research group of microbial natural substances([HIPS]MINS)
publications of the work group of molecular Infectionbiology (MIBI)