Biodistribution in mice and severity of damage in rat lungs following pulmonary delivery of 9-nitrocamptothecin liposomes.
This study was designed to investigate in vitro release, in vivo tissue distribution and the damage to the lungs of 9-nitrocamptothecin (9-NC) liposomes. In vitro release of 9-NC from liposomes was carried out in phosphate buffer saline solution (PBS) pH 7.4. The tissue distribution of 9-NC liposomes and 9-NC solution was determined after pulmonary delivery to mice. The tissue distribution of 9-NC liposomes after intravenous administration was also studied. The changes of pulmonary edema index and histology of lungs in rats were investigated to evaluate the severity of the damage after pulmonary delivery. The results showed that 9-NC was continuously released from liposomes in PBS pH 7.4 for 24h at 37 degrees C. After pulmonary delivery, the mean residence time (MRT) of 9-NC liposomes in the lungs was 3.4 times as long as that of 9-NC solution and the total AUC0-t of all tissues in mice of the liposomes was 2.2-fold higher than that of the solution, indicating that the liposomes had sustained-release characteristics. Following intravenous administration and pulmonary delivery, the targeting efficiency (Te) to the lung of 9-NC liposomes was 0.14 and 2.02, respectively, which showed that intratracheal instillation can deliver the drug mainly to the lung and decrease the accumulation of the drug in other tissues at different concentrations. The pulmonary edema index and the histological changes of the lungs in 9-NC liposome group were significantly different from those in 9-NC solution group. The lung damage by liposomes was less severe than that by solution. Pulmonary delivery of 9-NC liposomes could directly deliver the drug to the lung and make the drug accumulate in the lung with sustained-release characteristics, changing the disposition behavior in vivo, decreasing the toxic and side effects on other tissues and reduce the severity of damage to lungs following intratracheal instillation.
Zhang
Li-Jun
LJ
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Xing
Bin
B
Wu
Jiang
J
Xu
Bai
B
Fang
Xiao-Ling
XL
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004333:Drug Administration Routes; D005260:Female; D066298:In Vitro Techniques; D008081:Liposomes; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; C079905:rubitecan; D002166:Camptothecin