Preparation and optimization of pravastatin-naringenin nanotransfersomes to enhance bioavailability and reduce hepatic side effects

The present investigation was undertaken to develop a statistically and optimized omega-3-phospholipid based nanotransfersomes [NTFs] loaded with Pravastatin sodium [PVS] and Naringin [NG] in order to reverse the PVS induced hepatic marker enzymes elevation, decrease lipid peroxidation, and enhance the anti-oxidant cascade. NTFs were developed by a modified thin-film hydration technique using omega-3- phospholipids and sodium deoxycholate. The composition of the NTFs was statistically optimized by the design of Experiments using Box-Behnken design with three factors at three levels. They were characterized for size, EE%, ex-vivo permeation, and in-vivo hepatic markers enzymes level estimation. Omega-3-phospholipid has the most prominent effect on the particle size, followed by sodium deoxycholate. However, EE [%] is mostly affected by sodium deoxycholate, followed by omega-3-phospholipid. The optimized NTFs showed particle size, EE%, and cumulative % permeation of 191 nm, 76% and 55% respectively. The in-vivo study of optimized formulation revealed that NG act synergistically with omega-3-phospholipids, and potentially reverse the hepatic marker enzymes [ALT], and lipid peroxidative markers [MDA] induced by PVS to 54 IU/L and 45 mmol/mg protein respectively.