PEGylated meloxicam-loaded nanocapsules reverse in vitro damage on caspase activity and do not induce toxicity in cultured human lymphocytes and mice

• Published in: Biomedicine & pharmacotherapy 2018-11, Vol.107, p.1259-1267
• Main Authors: Nishihira, Vivian S.K., Fontana, Barbara D., Ianiski, Francine R., de Almeida, Hemilaine S., Posser, Christopher P., Dias, Juliane B., Parodi, Crystian B., Piva, Manoela M., Gris, Anderson, Mendes, Ricardo E., Duarte, Marta M.M.F., Sagrillo, Michele R., Luchese, Cristiane, Rech, Virginia C., Vaucher, Rodrigo A.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Body Weight - drug effects; Caspases - metabolism; Cell Survival - drug effects; Cell viability; Cells, Cultured; DNA Damage; Eating - drug effects; Humans; Hydrogen Peroxide - toxicity; Lymphocytes - drug effects; Lymphocytes - enzymology; Lymphocytes - pathology; Male; Meloxicam - pharmacology; Meloxicam - toxicity; Mice; Mice, Inbred C57BL; Nanocapsules - chemistry; Nanoparticles; Nanotoxicology; Non-steroidal anti-inflammatory; Organ Specificity; PEGylated; Polyethylene Glycols - chemistry; Spleen - drug effects; Spleen - pathology; Toxicity Tests
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.08.120

•M-NCPEG and M-NC did not alter toxicological parameters in vitro and in vivo models.•H2O2-inducing damage was partially reverted by M-NCPEG and M-NC.•M-NCPEG is safe to be used as an alternative treatment for inflammatory-related diseases. Meloxicam is an anti-inflammatory drug that has a potential protective effect in many common diseases. However, this molecule is quickly eliminated from the body due to it short half-life. One way to overcome this problem is to incorporate meloxicam into lipid-core nanocapsules which may increase it anti-inflammatory effects. In view of this, the objective of this work was to evaluate the potential toxicity and safety of these novel nanomaterials both in vitro and in vivo. Here, we evaluated the effects of uncoated meloxicam-loaded nanocapsules (M-NC), uncoated and not loaded with meloxicam or blank (B-NC), PEGylated meloxicam-loaded lipid-core nanocapsules (M-NCPEG), blank PEGylated lipid-core nanocapsules (B-NCPEG) and free meloxicam (M-F) in vitro through the analysis of cell viability, caspase activity assays and gene expression of perforin and granzyme B. Meanwhile, the in vivo safety was assessed using C57BL/6 mice that received nanocapsules for seven days. Thus, no change in cell viability was observed after treatments. Furthermore, M-NC, M-NCPEG and M-F groups reversed the damage caused by H2O2 on caspase-1, 3 and 8 activities. Overall, in vivo results showed a safe profile of these nanocapsules including hematological, biochemical, histological and genotoxicity analysis. In conclusion, we observed that meloxicam nanocapsules present a safe profile to use in future studies with this experimental protocol and partially reverse in vitro damage caused by H2O2.