Cationic Liposome Formulations Of Tenofovir And Their Role In Enhancing Hepatocyte Uptake

Tenofovir, a nucleotide analogue of adenosine monophosphate, has potent inhibitory activities against human immunodeficiency virus as well as hepatitis B virus. In order to enhance the therapeutic efficacy of tenofovir in treating Chronic HBV infection and reduce nephrotoxicity, we attempted to develop a novel liposome formulation that can deliver the drug more efficiently into hepatocytes.For preparing the liposomal formulation, ethanol was added to blank liposome solution with vigorous mixing to reach the final concentration 30%(v/v). Tenofovir solution was then slowly added under vortexing and the mixture was incubated for 1h and dialyzed to remove the ethanol. The tenofovir encapsulated liposomes and the free drugs were separated by Sephadex column filtration and assayed by HPLC. The encapsulation efficiencies were evaluated and various lipid compositions were screened for optimum drug loading and encapsulation efficeincy. Factors such as drug lipid ratio, cationic lipids structure were evaluated. The optimized recipe of liposome was [DSPC:CHOL:DMTAP:Cerebrosides:DSPE-PEG (6:3:2:1:0.5), drug:lipid(0.03)] and the encapsulation efficiency was about 86.05±2.20%. The size distribution and zeta potential were measured by PCS. The size and polydispercity index of the liposomes were 278.4±67.6nm and 0.117-0.350 respectively and the Zeta potential was about 31±5 mV. The samples can be stored stably for more than 1 month in the 4℃HEPES solution.To investigate the effect of liposome formulation in promoting hepatocyte uptake of tenofovir, human hepatic carcinoma cells SMMC-7721 were used as a model. The results showed that the liposomal formulations resulted in enhanced drug...