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.