Journal
NANOTECHNOLOGY
Volume 28, Issue 5, Pages -Publisher
IOP PUBLISHING LTD
DOI: 10.1088/1361-6528/aa5188
Keywords
nanohydrogels; chitosan; DLS; AF4; AFM-PFQNM; MRI contrast agents
Funding
- ANR [ANR-13-ENM2-0001-01]
- Region Wallone [1317980]
- Romanian National Authority for Scientific Research CCCDI-UEFISCDI [4-006/2014]
- Region Champagne Ardenne
- DRRT Champagne Ardenne (through MESR)
- EU-program FEDER (Project NanoBio2, Nano'Mat Platform)
- ARC [AUWB-2010-10/15-UMONS-5]
- FNRS
- ENCITE program
- COST TD1004 (Theranostics imaging and therapy: an action to develop novel nanosized systems for imaging-guided drug delivery)
- UIAP VII program
- Center for Microscopy and Molecular Imaging (CMMI - European Regional Development Fund)
- Microscopy and Molecular Imaging (CMMI - Walloon Region)
- French National Agency for Research called 'Investissements d'Avenir', Equipex Arronax-Plus [ANR-11-EQPX-0004]
- French National Agency for Research called 'Investissements d'Avenir', Labex [ANR-11-LABX-0018-01]
- Agence Nationale de la Recherche (ANR) [ANR-13-ENM2-0001] Funding Source: Agence Nationale de la Recherche (ANR)
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Chitosan CS-tripolyphosphate TPP/hyaluronic acid HA nanohydrogels loaded with gadolinium chelates (GdDOTA subset of CS-TPP/HA NGs) synthesized by ionic gelation were designed for lymph node (LN) MRI. In order to be efficiently drained to LNs, nanogels (NGs) needed to exhibit a diameter phi < 100 nm. For that, formulation parameters were tuned, using (i) CS of two different molecular weights (51 and 37 kDa) and (ii) variable CS/TPP ratio (2 < CS/TPP < 8). Characterization of NG size distribution by dynamic light scattering (DLS) and asymetrical flow-field-flow-fractionation (AF4) showed discrepancies since DLS diameters were consistently above 200 nm while AF4 showed individual nano-objects with phi < 100 nm. Such a difference could be correlated to the presence of aggregates inherent to ionic gelation. This point microscopy (AFM) in liquid mode which highlighted the main presence of individual nano-objects in nanosuspensions. Thus, combination of DLS, AF4 and AFM provided a more precise characterization of GdDOTA subset of CS-TPP/HA nanohydrogels which, in turn, allowed to select formulations leading to NGs of suitable mean sizes showing good MRI efficiency and negligible toxicity.
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