Abstract

In this work, we designed a drug delivery nanosystem based on oil-in-water Pluronic F127 nanomicelles to encapsulate and control the release of the antineoplasic drug carfilzomib (CFZ), and hypothesized that CFZ entrapment might result in a better effective and more localized cytotoxic effect on cancerous cells and to reduce its undesirable side effects for in vitro and in vivo applications. Pluronic F127/CFZ nanomicelles showed a high drug encapsulation efficiency (74.8%) and were allowed to achieve a sustained release pattern. Computational analyses were conducted to increase understanding of the nature and strength of mutual interactions between Pluronic F127 and CFZ. Simulation data indicated that the position of heteroatoms on CFZ influences the strength of attractive interactions in the Pluronic F127/CFZ nanomicelles. Cytotoxic activity of free and encapsulated CFZ was assayed in several cancerous cell lines, SHY-SY5Y human neuroblastoma, MCF7 breast, and HeLa cervical cancer cells employing the MTT colorimetric assay. We found that Pluronic F127/CFZ nanomicelles exhibited greater anti-proliferative activity than free CFZ (lower IC50s) and induced evident morphological alterations in cancer cells. Caspase-3 activity was assessed to determine the main mechanism of drug-induced cell death. Compared to free CFZ, our formulation only increased caspase-3 activity in HeLa cells. To examine the short-term toxicity of F127/CFZ nanomicelles, intravenous injections of free CFZ and F127/CFZ nanomicelles at three doses of 0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg for five consecutive days were administered to an animal model. The potential anti-bactericidal activity of this new formulation was also assayed against four standard bacteria, including Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. Unfortunately, no significant bacteria-killing effects were detected despite other drugs of the same family showing promising results. Still, our new formulation showed desirable anti-cancer effects and might be a good therapeutic modality for cancer treatment. © 2021 Elsevier B.V.