Tissue distribution, pharmacokinetics and stability studies of zidovudine delivered by niosomes and proniosomes.
Niosomes containing zidovudine (ZDV), an anti-HIV drug for intravenous administration were formulated by a thin-film hydration technique. Proniosomes were prepared in the form of a slurry using beta-cyclodextrin as carrier. The effect of the surfactants Tween and Span and the negative charge-inducing agent dicetylphosphate (DCP) on tissue distribution of niosomes and proniosomes was studied. The distribution of ZDV in lungs, kidney, heart, liver and spleen of mice after intravenous bolus injection was higher in Tween 80 niosomes without DCP than either niosomes with DCP or Tween 80 proniosomes. The amount of ZDV in plasma was low in Tween 80 niosomes without DCP. The results of a pharmacokinetic study in rabbits confirmed that Tween 80 formulations with DCP were cleared from the circulation within five hours. An increased half-life of 202 minutes and mean residence time of 212.1 minutes was observed in Tween 80 formulation. A stability study showed that after 90 days of storage, the drug leakage from Tween 80 formulations stored at room temperature was significant (p < 0.001) compared to niosomes stored at 4 degrees C. Encapsulation ZDV in proniosomes reduced drug leakage from vesicles stored at room temperature. These results demonstrate that niosomes are a promising vehicle for targeted delivery of ZDV to macrophages in spleen and liver.
Ruckmani
Kandasamy
K
Department of Pharmaceutical Technology, Anna University Tiruchirappalli, Tamilnadu 620024, India.
Sankar
Veintramuthu
V
Sivakumar
Manickam
M
D000704:Analysis of Variance; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D006207:Half-Life; D008081:Liposomes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D010316:Particle Size; D011136:Polysorbates; D011817:Rabbits; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D015215:Zidovudine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D008081:Liposomes; D011136:Polysorbates; D015215:Zidovudine