Development and Evaluation of Febuxostat Loaded D-α-tocopheryl Polyethylene Glycol 1000 Succinate Micelles for Lung Cancer

Mohammad Y. Alfaifi, Ali A. Shati, Serag Eldin I. Elbehairi, Usama A. Fahmy, Nabil A. Alhakamy and Shadab Md.

Background and Objective: Febuxostat (FBX) is a proven prophylactic agent in the management of tumor lysis syndrome in patients with malignant tumors. The clinical application of FBX is hindered due to poor solubility and bioavailability. The purpose of the present study was to develop miceller delivery of FBX using an amphiphilic and non-ionic macromolecule, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for the treatment of lung cancer. Materials and Methods: FBX-loaded TPGS micelles (TPGS-FBX-M) were formulated by thin-film hydration method and are characterized for particle size and morphology using dynamic light scattering techniques and transmission electron microscopy. Developed miceller formulation of FBX (TPGS-FBX-M) was further evaluated for entrapment efficiency and in vitro release. Results: Nano-sized spherical miceller deliveries of TPGS-FBX-M displayed a release of 72.7% within 12 h. The formulation was employed to assess cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549), where TPGS-FBX-M micelles were found to reduce IC50 values as compared to free FBX which might be due to increased uptake of FBX and effectiveness against A549 cells. An increased cell cycle blockade at the G2/M phase improved apoptotic activity and a significant increase in the expression of caspase 3 for TPGS-FBX-M as compared to free FBX incubation in vitro. Conclusion: This impressive drug delivery platform for lipophilic agents can also be used to deliver other hydrophobic chemotherapeutics to target cancer cells for improves efficacy and safety.

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