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Open AccessArticle

Biodistribution and Biosafety of a Poly(Phosphorhydrazone) Dendrimer, an Anti-Inflammatory Drug-Candidate

1
INSERM, U1043, CNRS, U5282, Université de Toulouse, UPS, Centre de Physiopathologie de Toulouse-Purpan, F-31300 Toulouse, France
2
CNRS, UMR 5089, Université de Toulouse, UPS, Institut de Pharmacologie et de Biologie Structurale, IPBS, 205 route de Narbonne, BP 64182, F-31077 Toulouse CEDEX 4, France
3
CNRS, UPR 8241, Laboratoire de Chimie de Coordination, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France
4
LCC-CNRS, Université de Toulouse, CNRS, Toulouse, France
5
CNRS, UMR 5623, Université de Toulouse, UPS, Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique, IMRCP, 118 route de Narbonne, F-31062 Toulouse CEDEX 9, France
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(9), 475; https://doi.org/10.3390/biom9090475
Received: 31 July 2019 / Revised: 2 September 2019 / Accepted: 6 September 2019 / Published: 11 September 2019
Dendrimers are nanosized, arborescent polymers of which size and structure are perfectly controlled. This is one reason why they are widely used for biomedical purposes. Previously, we showed that a phosphorus-based dendrimer capped with anionic azabisphosphonate groups (so-called ABP dendrimer) has immuno-modulatory and anti-inflammatory properties towards human immune cells in vitro. Thereafter, we have shown that the ABP dendrimer has a promising therapeutic efficacy to treat models of chronic inflammatory disorders. On the way to clinical translation, the biodistribution and the safety of this drug-candidate has to be thoroughly assessed. In this article, we present preliminary non-clinical data regarding biodistribution, hematological safety, genotoxicity, maximal tolerated doses, and early cardiac safety of the ABP dendrimer. One of the genotoxicity assays reveals a potential mutagen effect of the item at a concentration above 200 µM, i.e., up to 100 times the active dose in vitro on human immune cells. However, as the results obtained for all the other assays show that the ABP dendrimer has promising biodistribution and safety profiles, there is no red flag raised to hamper the regulatory pre-clinical development of the ABP dendrimer. View Full-Text
Keywords: azabisphosphonate; biodistribution; dendrimers; drug candidate; preclinical development; rabbit; rodents; safety azabisphosphonate; biodistribution; dendrimers; drug candidate; preclinical development; rabbit; rodents; safety
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Fruchon, S.; Bellard, E.; Beton, N.; Goursat, C.; Oukhrib, A.; Caminade, A.-M.; Blanzat, M.; Turrin, C.-O.; Golzio, M.; Poupot, R. Biodistribution and Biosafety of a Poly(Phosphorhydrazone) Dendrimer, an Anti-Inflammatory Drug-Candidate. Biomolecules 2019, 9, 475.

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