In vivo Bio-Distribution and Toxicity Evaluation of Polymeric and Lipid-Based Nanoparticles: A Potential Approach for Chronic Diseases Treatment

João Fonseca-Gomes,^1,2,* Joana A Loureiro,^3,* Sara R Tanqueiro,^1,2 Francisco M Mouro,^1,2 Pedro Ruivo,² Tânia Carvalho,² Ana M Sebastião,^1,2 Maria José Diógenes,^1,2,* Maria Carmo Pereira<sup>1– 3,*

1</sup>Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal; ²Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal; ³LEPABE – Laboratory for Process Engineering, Environment, Biotechnology & Energy, Faculty of Engineering, University of Porto, Porto 4200-465, Portugal

*These authors contributed equally to this work

Correspondence: Maria José Diógenes
Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Avenida Professor Egas Moniz, Lisbon 1649-028, Portugal
Email diogenes@medicina.ulisboa.pt
Maria Carmo Pereira
Faculty of Engineering, University of Porto, R. Dr. Roberto Frias, s/n, Porto 4200-465, Portugal
Email mcsp@fe.up.pt

Introduction: Nanoparticles (NPs), as drug delivery systems, appear to be a promising tool for prolonged therapeutic strategies as they allow a controlled drug release over time. However, most of the studies found in the literature simply contemplate the use of a single or low number of dosages with low NPs concentrations. In the context of chronic diseases, like Alzheimer’s disease, cancer or human immunodeficiency virus (HIV), where the therapeutic scheme is also chronic, studies with numerous repeated dosages are often neglected.
Methods: We screened different NPs, polymeric and lipid-based, in a repeated-dose toxicity study, to evaluate the safety and tissue distribution of promising nanocarriers to be used in the treatment of long-lasting diseases.
Results: After administrating 24 high concentrated doses of the selected NPs intraperitoneally (i.p.) (3 times a week for 2 months), animals have presented NPs accumulation in different tissues. However, neither toxicity, bodyweight changes nor clinical signs of disease were observed.
Discussion: This work demonstrates no general adverse effects upon the studied NPs repeated-dose exposure, indicating the most promising NPs to be used in the different therapeutic circumstances, which may be useful in chronic diseases treatment.

Keywords: long-lasting treatment, drug delivery systems, nanocarriers, liposomes, solid lipid nanoparticles, PLGA nanoparticles