Preparation of Lamivudinyl palmitate nanoemulsome for liver-targeting delivery

The water solubility and side effects of lamivudine limit its application for the treatment of viral hepatitis type B and human immunodeficiency virus. In order to increase the solubility of LA and improve the in vivo membrane permeability of the drug, LA was modified with hexadecane acid to prepare the prodrug lamivudine palmitic acid (LAP) and loaded into nanoemulsome (NES). LAP-NES was prepared by the thin film dispersion method. The LAP-NES showed the sustained release performance up to 72h in pH 7.4 PBS. Moreover, the pharmacokinetics of LAP-NES after tail vein injection in rats and the biodistribution characteristics were evaluated. The tmax of LAP-NES was 2.5h. The t1/2, clearance rate and average retention time of LAP-NES obviously prolonged compared with free LAP. The tissue biodistribution behavior of NES in vivo showed the good targeting in the liver and spleen, with the maximum at 4h and then the fluorescence slowly decreased until 72h. LAP-NES could significantly delay the release of LA in vivo, effectively prolong the elimination time and had obvious liver-targeting ability. In summary, LAP-NES shows great potential for liver-targeting delivery to increase the therapeutic effect and decrease the side effects of LA.