Deferasirox-loaded pluronic nanomicelles: Synthesis, characterization, in vitro and in vivo studies

Abstract

The development of biocompatible and biodegradable microemulsions to deliver drug molecules is a challenging task in pharmacological sciences. In this study, deferasirox (DEF) formulated into oil-in-water microemulsions in the presence of non-ionic Pluronic as a surfactant to improve its oral bioavailability with loading efficiency (73.0% ± 8.4). Size of the DFX-loaded microemulsions system by dynamic light scattering (DLS) was about 9 nm. In vitro cytotoxic effects of DFX and DFX-loaded microemulsions on Hep G2 (cancerous) and HUVEC (normal) cell lines were assessed using the tetrazolium-based colorimetric assay (MTT test). Based on MTT results, in Hep G2 cancer cells, DFX-loaded microemulsions exerted greater anti-proliferative effects than free DFX, while in HUVEC cells, encapsulated DFX induced less cytotoxicity. In order to compare the in vivo activities of free DFX and DFX-loaded microemulsions, rats received oral intubation of both solutions for six weeks. Oral gavage treatment of free DFX significantly increased serum ALT, AST, BUN, and creatinine compared to the serum parameters of healthy control rats. Free DFX treatment also increased serum and liver MDA levels. Treatment with DFX-loaded microemulsions did not induce a significant elevation in serum biochemical parameters and liver MDA content. Histopathological analysis of liver and kidney sections confirmed the biological data. Our results demonstrated Pluronic oil-in-water microemulsion as a safe and stable nanoformulation with a considerable potential for drug delivery.