[Preparation of PEG-modified nanostructured lipid carriers loaded with hydroxycamptothecin and tissue distribution in mice].
Hydroxycamptothecin (HCPT) loaded PEG modified nanostructured lipid carriers (HCPT-PEG-NLC) and nanostructured lipid carriers (HCPT-NLC) were prepared by melt emulsification and homogenization method. The morphology, particle size and encapsulation efficiency of them were investigated. HCPT concentrations in plasma, heart, liver, spleen, lung, kidney and ovary were determined after iv of HCPT injection, HCPT-PEG-NLC and HCPT-NLC in mice. The targeting indexes of HCPT-PEG-NLC and HCPT-NLC were calculated. The transmission electron microscope imaging showed that HCPT-PEG-NLC and HCPT-NLC exhibited a spherical shape. The particle sizes of them were (88.6 +/- 22.5) and (127.2 +/- 43.4) nm. The encapsulation efficiency were (90.51 +/- 3.29)% and (84.37 +/- 2.81)%, respectively. After iv injection into the tail vein of mice, HCPT plasma concentrations of HCPT-PEG-NLC and HCPT-NLC were higher than that of HCPT injection at each sampling time. They also showed longer elimination time in every tissue. HCPT-NLC accumulated in endothelial system (RES), Re and Ce of it in liver and spleen were significantly higher than HCPT-PEG-NLC. HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT. MRT and AUC0-24 h of it were 19.80 and 17.02 times higher than those of HCPT injection. It also significantly reduced phagocytosis of RES, and showed lung targeting effect (Re and Ce were 14.51 and 41.35). To summarize, HCPT-PEG-NLC could prolong the circulation time of HCPT in vivo, and had the lung targeting effect. It was a promising carrier to increase therapeutic effect of HCPT in treating lung cancer.
Zhang
Xin-Xin
XX
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Gan
Yong
Y
Yang
Xing-Gang
XG
Zhu
Chun-Liu
CL
Gan
Li
L
Nie
Shu-Fang
SF
Pan
Wei-San
WS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D008055:Lipids / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D051379:Mice; D012157:Mononuclear Phagocyte System / Q000502:physiology; D053758:Nanoparticles; D010316:Particle Size; D010587:Phagocytosis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D008055:Lipids; D011092:Polyethylene Glycols; C028098:10-hydroxycamptothecin; D002166:Camptothecin