Abstract

Background and Objective: Role of dietary phenolic compounds in the modification of pathophysiological conditions in cancer is immense. Thus, ellagic acid (EA), a natural polyphenolic compound has been recognized for its anticancer activity in different preclinical studies. However, clinical application is limited because of its poor aqueous solubility and thereby, inadequate oral bioavailability. The present work was aimed to formulate micellar delivery, an effective nano-delivery tool for EA, using D-α-tocopheryl polyethylene glycol succinate (TPGS) by film-hydration method. Materials and Methods: Film hydration method was introduced to encapsulate EA within the TPGS micellar structure, which was then characterized and evaluated for in vitro release study. EA-TPGS micelle was further exposed to OVACR3 to determine cancer protecting potential of the formulation. Results: The delivery system (EA-TPGS micelles) consists of spherical shape of 113.2±23 nm with 0.260±0.038 PDI and drug-encapsulation efficiency of 88.67%±3.21. In vitro release profile in the phosphate-buffer saline was found to observe sustained pattern with 67.8% cumulative release within 12 h. Further, a dose dependent cytotoxicity of EA-TPGS micelles was observed on OVACR3 cells with an IC50 value of 12.36 μM. EA-TPGS significantly reduced viable cells via arrest of G1 phase of cell cycle and thereby induce apoptosis probably through inhibiting p15 and p21. Decreased fluorescence unit in ROS determination assay also reflected potential antioxidant activity of the EA-TPGS. Conclusion: These findings strengthened that use of EA-TPGS micelles could overcome the limitations in delivery of hydrophobic chemotherapeutics through oral route.