[9-nitrocamptothecin nanostructured lipid carrier system: in vitro releasing characteristics, uptake by cells, and tissue distribution in vivo].
OBJECTIVE
To study the release and cell uptake characteristics of 9-nitrocamptothecin (9-NC) nanostructured lipid carrier system (NLC) in vitro and its tissue distribution characteristics in vivo.


METHODS
Mouse peritoneal macrophages were used to investigate the uptake of nanoparticles by cells in vitro. The tissue distribution of 9-nitrocamptothecin solution and stealth nanostructured lipid carrier system (S-NLC) was determined after intravenous administration to mice at a single dose of 1.5 mg kg(-1). The release and crystalloid characteristics were also investigated.


RESULTS
X-ray diffraction spectrum showed that 9-NC probably was amorphous in S-NLC. The liquid lipid did not change the characteristics of the solid matrix in nanoparticles. The in vitro release and cell uptake characteristics of stealth and non-stealth 9-NC-NLC were investigated, separately. The results showed that the stealth 9-NC-NLC had sustained-release characteristics and could resist the absorption effect of the additional plasmas to a certain extent. In addition, the cell uptake percentage of stealth 9-NC-NLC was much lower than that of the non-stealth ones. The tissues distribution results showed that 9-NC in the S-NLC was mainly found in the lung, liver, pancreas and ovary/uterus, while the quantity of 9-NC was much lower in heart and kidney. The AUQ(0-t), of S-NLC in blood, ovary/uterus, pancreas, liver and lung were higher than that of 9-nitrocamptothecin solution. The weight-average drug targeting efficiency (Te*) of S-NLC in liver and lung were significantly higher than that of 9-nitrocamptothecin solution. The mean residence times (MRT) of S-NLC was 44 h, while that of 9-nitrocamptothecin solution was 8 h. Therefore, S-NLC showed obvious targeting effects on liver and lung.


CONCLUSIONS
S-NLC with PEG flexible chains has sustained-release characteristics and can prolong its circulation in blood and have good targeting efficiency on liver and lung.
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, China.
Jun-chan
JC
Li
Xian-yi
XY
Sha
Li-jun
LJ
Zhang
Xiao-ling
XL
Fang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D006601:Hexoses / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000502:physiology*; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010587:Phagocytosis; D010713:Phosphatidylcholines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006601:Hexoses; D010713:Phosphatidylcholines; D011092:Polyethylene Glycols; C009314:polyethylene glycol monostearate; C079905:rubitecan; C009298:sorbitan monostearate; D002166:Camptothecin