ABSTRACT
The aim of this work was to investigate the in vitro cytotoxic effect of previously developed nanocapsules, nanoemulsion, and microemulsion based on bullfrog oil (BFO) against human melanoma cells (A2058). The nanosystems were produced as described in previous studies and characterized according to droplet/particle distribution and zeta potential. The biocompatibility was evaluated by the determination of the hemolytic potential against human erythrocytes. The cytotoxicity assessment was based on MTT and cell death assays, determination of Reactive Oxygen Species (ROS) levels, and cell uptake. The nanosystems were successfully reproduced and showed hemolytic potential smaller than 10% at all oil concentrations (50 and 100 µg.mL-1) (p < 0.05). The MTT assay revealed that the nanosystems decreased the mitochondrial activity up to 92 ± 2% (p < 0.05). The study showed that the free BFO induced cell apoptosis, while all the nanostructured systems caused cell death by necrosis associated with a ROS overproduction. This can be related to the increased ability of the nanostructured systems to deliver the BFO across all cellular compartments (membrane, cytoplasm, and nucleus). Finally, these results elucidate the in vitro BFO nanosystems cytotoxic effect against human melanoma cells (A2058), revealing the emulsified ones as the most cytotoxic systems. Overall, the findings suggest that the safety and antineoplastic activity of these systems can be further investigated by in vivo studies.
Subject(s)
Antineoplastic Agents/pharmacology , Melanoma/drug therapy , Nanostructures , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Cell Line, Tumor , Emulsions , Erythrocytes/drug effects , Erythrocytes/metabolism , Hemolysis/drug effects , Humans , Melanoma/pathology , Mitochondria/metabolism , Nanocapsules , Oils/isolation & purification , Oils/pharmacology , Oils/toxicity , Particle Size , Rana catesbeiana/metabolism , Reactive Oxygen Species/metabolism , Skin Neoplasms/pathologyABSTRACT
Poorly soluble active pharmaceutical ingredients (APIs) create major problems in drug dosage form formulation resulting in significant delays in drug pharmaceutical screening, impairing the drug dosage form production. Aiming to minimize the use of excipients for increasing drug apparent solubility and, as a result, its bioavailability, exploration of innovative approaches is an earnest need. Microemulsion is an alternative drug delivery system that emerged as a valuable tool to achieve safe formulations for insoluble compounds and to improve their biopharmaceutical properties and pharmacokinetics. This review aims to present the state of the art of microemulsion systems, bringing an overview about their origin and how they can be properly produced and thoroughly characterized by different approaches. Furthermore, comments on regulatory issues regarding stability assessment and toxicity evaluation are discussed. The review concludes with a current opinion on microemulsion systems. The overall objective of this work was to describe all the potentialities of microemulsion systems as a drug carrier for therapeutic purposes, highlighting the unique features of this nanotechnological platform. Display Image.