Study On Azidothymidine Palmitate Nanoemulsion

The method of HPLC was established to determine Azidothymidine palmitate(AZTP) in nanoemulsion. Processing factors were studied by single factor test and orthogonal experimental design and the best formulation and technique were optimized. AZTP nanoemulsion obtained was a milky, semitransparent and homogeneous phase system and the mean diameter was 55.3±26.0nm.The physical and the chemical stability of AZTP nanoemulsion were respectively studied Simultaneously, the stability of AZTP nanoemulsion in diluents was investigated. It was found that AZTP nanoemulsion should be stored at lower temperature avoiding light and be diluted with glucose injection.The HPLC method of parent compound AZT in mice was established and the AZT concentration in the plasma and tissues of the mice was determined. The amount of drug distribution in plasma and tissues was examined after intravenous administration of AZTP nanoemulsion and AZTP solution. The results show that tissue targeting efficiency of AZTP nanoemulsion was 1.02 times, 1.05 times, 1.90 times, 1.52 times, 1.10 times, 0.52 times and 1.78 times of that of AZTP solution in plasma, heart, liver, spleen, lung, kidney and brain respectively. AZTP nanoemulsion significantly increased the amount of drug distribution in liver, spleen and brain, decreased the amount of drug distribution in kidney, compared with AZTP solution.Two kinds of modified AZTP nanoemulsion (galactosylated AZTP nanoemulsion and PEG modified galactosylated AZTP nanoemulsion) were prepared and compared with conventional AZTP nanoemulsion to examine effects of targeting adjuvant. The pharmacokinetics parameters were fitted and calculated by Topfit program. The results show that modified AZTP nanoemulsion significantly increased the amount of drug distribution in liver and possessed liver targeting character.