Development and characterization of a temozolomide-loaded nanoemulsion and the effect of ferrocene pre and co-treatments in glioblastoma cell models.

BACKGROUND: Glioblastoma is a severe brain tumor that requires aggressive treatment involving surgery, radiotherapy, and chemotherapy, offering a survival rate of only 15 months. Fortunately, recent nanotechnology progress has enabled novel approaches and, alongside ferrocenes' unique properties of cytotoxicity, sensitization, and interaction with reactive oxygen species, have brought new possibilities to complement chemotherapy in nanocarrier systems, enhancing treatment results. METHODS: In this work, we developed and characterized a temozolomide-loaded nanoemulsion and evaluated its cytotoxic potential in combination with ferrocene in the temozolomide-resistant T98G and temozolomide-sensitive U87 cell lines. The effects of the treatments were assessed through acute assays of cell viability, cell death, mitochondrial alterations, and a treatment protocol simulation based on different two-cycle regimens. RESULTS: Temozolomide nanoemulsion showed a z-average diameter of 173.37 ± 0.86 nm and a zeta potential of - 6.53 ± 1.13 mV. Physicochemical characterization revealed that temozolomide is probably associated with nanoemulsion droplets instead of being entrapped within the nanostructure, allowing a rapid drug release. In combination with ferrocene, temozolomide nanoemulsion reduced glioblastoma cell viability in both acute and two-cycle regimen assays. The combined treatment approach also reversed T98G's temozolomide-resistant profile by altering the mitochondrial membrane potential of the cells, thus increasing reactive oxygen species generation, and ultimately inducing cell death. CONCLUSIONS: Altogether, our results indicate that using nanoemulsion containing temozolomide in combination with ferrocene is an effective approach to improve glioblastoma therapy outcomes.

Polymeric nanoparticles containing babassu oil: A proposed drug delivery system for controlled release of hydrophilic compounds.

Different drug delivery systems are prepared on the nanoscale to improve performance in drug formulations, such as nanoparticles or nanoemulsions. Polymeric nanoparticles have been used to encapsulate drugs for several applications because of some characteristics of these carriers to control drug delivery, transport molecules to a specific tissue, protect the drugs, and increase drug bioavailability. When using nanocapsules, an essential parameter for encapsulating different hydrophilic or lipophilic molecules is the characteristics of the core. Babassu oil (BBS) is a natural product from Brazil, composed majoritary of short-chain saturated fatty acids. BBS has an elevated hydrophilic-lipophilic balance (HLB), which may promote interaction of the oil with hydrophilic drugs. In this study, we developed and characterized particles containing babassu oil, solely or combined with sorbitan monostearate (Span® 60) or medium chain triglycerides (MCT) in the core to test different HLB and evaluated the encapsulation of a model hydrophilic molecule. Different techniques were used to characterize all formulations in terms of size and distribution, and in vitro drug release by dialysis technique was performed. The BBS was also characterized and presented 46,05 ± 1,11% and 15,38 ± 0,06% of lauric and myristic acid, respectively; saponification index of 248.87 ± 0.64 mg of KOH per gram of BBS, and no oxidation of the oil was indicated by means of peroxide index. Evaporation of solvent carried in the room or reduced pressure influenced the particles' size; nevertheless, all had a z-average smaller than 220 nm. Nanoparticles with a ratio among aqueous phase and organic phase of 2.8 were considered adequate to encapsulate diclofenac sodium. The particles size/zeta potential were 189.83 ± 7.86 nm / - 10.39 ± 2.52 mV, 156.80 ± 4.77 nm / - 9.27 ± 4.61 mV, and 168.87 ± 5.22 nm / - 12.98 ± 4.66 mV to nanoparticles prepared with BBS + MCT, BBS, and BBS + Span® 60, respectively. All formulations exhibited an amount of drug content close to the theoretical amount (1.0 mg mL-1), and no difference was observed in the release profile among the three nanoparticles. Formulation containing only babassu oil in the core displayed 66.78 ± 15.62% of encapsulation efficiency to diclofenac sodium, the highest value among all formulations tested. Results demonstrate that the innovative nanoparticles containing BBS promote the encapsulation of a model hydrophilic molecule, and other components can be evaluated to change the core's hydrophilicity and encapsulation of molecules.