Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer.

Abstract

To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis. Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model. Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer. Imiquimod administration through abigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.