Lipid nanoparticles loaded with 10-hydroxycamptothecin-phospholipid complex developed for the treatment of hepatoma in clinical application.
For the purpose of clinical intravenous injection of 10-hydroxycamptothecin, a novel formulation of lipid nanoparticles loaded with 10-hydroxycamptothecin-phospholipid complex (HCPT-PC-LNs) was prepared by solvent evaporation and high-pressure homogenization methods. Spherical particles with a mean particle size of 200 nm and high encapsulation efficiency of 97.39 +/- 0.91% could be achieved under optimal conditions. In vitro release profile showed that the release pattern of HCPT from nanoparticles was retarded with neglectable initial burst release and well-fitted to Ritger-Peppas equation. In vivo distribution studies in mice showed that HCPT-PC-LNs were mainly localized in liver. Besides, in situ mouse hepatoma model was established and tumor uptake of HCPT-PC-LNs was much higher than that of free HCPT (more than 18-fold). It was found that HCPT-PC-LNs exhibited high growth inhibitory effect on human liver cancer cells by MTT assay. The cellular uptake of HCPT was 24.33 +/- 1.30 x 10(-7) microg/cell in HCPT-PC-LNs treated group at 12 h, which was almost 14-fold higher than that of free HCPT (1.72 +/- 0.57 x 10(-7) microg/cell). This study suggested that the HCPT-PC-LNs could be utilized as a novel formulation for liver tumors therapy, which might be applied in clinic in the near future.
Wei
Wei
W
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Sichuan, People's Republic of China.
Shi
San-Jun
SJ
Liu
Jie
J
Sun
Xun
X
Ren
Ke
K
Zhao
Dong
D
Zhang
Xiao-Ning
XN
Zhang
Zhi-Rong
ZR
Gong
Tao
T
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010743:Phospholipids; C028098:10-hydroxycamptothecin; D002166:Camptothecin