Pluronic F127/Doxorubicin microemulsions: Preparation, characterization, and toxicity evaluations

• Synthesis of Pluronic F127 microemulsions to enhance the bioavailability of doxorubicin (DOX). • Quantum theory of atoms in molecules (QTAIM) analysis to determine the nature of interactions. • DOX microemulsion size was about 7.0 nm by dynamic light scattering analysis. • In vitro toxicity of DOX-loaded microemulsions were assessed on MCF-7, C152 and HUVEC cell lines. • New drug delivery system formulation shows promise for cancer treatment. The development of drug delivery systems minimizing the side effects of conventional chemotherapy is one of the major challenges in the field of biomaterials for cancer treatment. This work reports the formulation and characterization of oil-in-water Pluronic F127 microemulsions to enhance the bioavailability of doxorubicin (DOX). The density functional theory (DFT) calculations at the M06-2X level of theory were done to study the interaction details of DOX with ethyl butyrate, sodium caprylate, and one unit of the polymeric chain of surfactant Pluronic F127 in water solution, which are used in the synthesis process. Specifically, the quantum theory of atoms in molecules (QTAIM) analysis was performed to determine the nature of interactions. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were calculated to show the direction of charge transfer within each complex. Furthermore, the natural bond orbital (NBO) analysis was performed on the studied systems. The size of F127/DOX microemulsion was about 7.0 nm by dynamic light scattering analysis. In vitro toxicity of standard DOX and DOX-loaded microemulsions were assessed against MCF-7 and C152 (malignant) and HUVEC (non-malignant) cell lines. Intracellular lactate dehydrogenase (LDH) leakage was evaluated as an indicator of membrane integrity. In vitro assessments revealed that Pluronic F127/DOX microemulsions caused substantial morphological changes and greater cytotoxic effects than standard DOX. Pluronic F127/DOX microemulsions were injected intraperitoneally at 12 and 24 mg/kg into rats. The free (bulk) DOX group induced severe histopathological changes and significant increases in serum kidney markers and serum liver enzymes. The 24 mg/kg dose of Pluronic F127/DOX microemulsions also induced fatty changes and elevation of serum liver enzymes and creatinine. Overall, this new drug delivery system formulation shows promise for cancer treatment and deserves to be further studied in the future.