Development of nanobigel system combining apoptosis-inducing daidzein and flaxseed oil for the synergistic treatment of skin cancer

Abstract

Daidzein (DDZ), an isoflavone containing phytoestrogen, and flaxseed oil (FSO), an omega-3-polyunsaturated fatty acid rich dietary lipid, are known to exert anticancer effects via inducing apoptosis in cancer cells. However, oral administration of DDZ and FSO is associated with biopharmaceutical issues. This study aimed to develop a stable topical bigel (BG) system containing DDZ and FSO to exert synergistic effects in the treatment of skin cancer. High speed homogenization method was used for the preparation of DDZ-loaded bigel (DDZ@BG). In vitro investigations and morphological studies were performed to characterize the developed formulation. MTT cytotoxicity tests were conducted to evaluate the effect of the combination of DDZ and FSO on A431human skin cancer cell lines. To assess the toxicity, skin irritation studies using the Draize test was performed followed by histopathological analysis. The optimized DDZ@BG exhibited uniform texture, nanometric size and high drug content with sustained release profile and improved drug permeation. The MTT cytotoxicity studies revealed an IC50 value of 110.2 μg/mL for the optimized formulation. The developed nanobigel formulation exhibited high potential in the effective topical treatment of skin cancer with improved safety profile.