Toxicity and biodistribution of orally administered casein nanoparticles
Gil AG (1), Irache JM (2), Peñuelas I (3), González Navarro CJ (4), López de Cerain A (5).
1 (a) Department of Pharmacology and Toxicology, Drug Development Unit, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
2 (b) Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
3 (c) Radiopharmacy Unit, Clínica Universidad de Navarra, 31008 Pamplona, Spain.
4 (d) Centro Nacional de Tecnología y Seguridad Alimentaria, 31570, San Adrian, Spain.
5 (a) Department of Pharmacology and Toxicology, Drug Development Unit, Faculty of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds.However, till now, no information about their possible specific hazards in vivo was available.
The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found.
This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females.
These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day.
CITATION Food Chem Toxicol. 2017 Jun 10. pii: S0278-6915(17)30328-9. doi: 10.1016/j.fct.2017.06.020