Carvone Schiff base of isoniazid as a novel antitumor agent: Nanoemulsion development and pharmacokinetic evaluation

In the present study, various nanoemulsion formulations of carvone Schiff base of isoniazid (CSB-INH) were developed by aqueous phase titration method in order to evaluate its anticancer potential. Developed nanoemulsions of CSB-INH were characterized in terms of thermodynamic stability, self-nanoemulsification efficiency, droplet size, polydispersity index (PI), zeta potential (ZP), viscosity, refractive index (RI), % transmittance (%T), surface morphology and in vitro drug release studies. Based on lowest droplet size (19.4 nm), least PI(0.189), lowest viscosity (29.6 cP), optimal values of ZP (-30.8 mV) & RI (1341), highest %T (98.9%), highest drug release profile (94.5% after 24 h) and the presence of lowest concentration of Triacetin (12% w/w), formulation N1 was selected for in vitro cytotoxicity and in vivo pharmacokinetic studies. Cytotoxicity studies on human colon cancer cells indicated that CSB-INH in optimized nanoemulsion is around nine times more efficacious than free CSB-INH. Pharmacokinetic studies in Albino rats showed rapid absorption (rate and extent) of CSB-INH from optimized nanoemulsion as compared to its suspension formulation. These results indicated the potential of developed nanoemulsion for oral delivery of CSB-INH for chemoprevention of colon cancer. (C) 2014 Elsevier B.V. All rights reserved.