Preparation of irinotecan-loaded folate-targeted liposome for tumor targeting delivery and its antitumor activity.
The purpose of this study was to investigate the in vivo distribution and antitumor activity of irinotecan (camptothecin (CPT)-11)-loaded folate-targeted liposome (F-Lip) in tumor-bearing mice following i.v. administration. Folate-poly(ethylene glycol)-distearoylphosphatidylcholine (FA-PEG-DSPE) was synthesized by amide reaction of DSPE-PEG-NH(2) and FA. F-Lip modified by FA-PEG-DSPE was prepared by an ammonium sulfate gradient. The mean particle size and entrapment efficiency of F-Lip with negative charge were 197.8 ± 4.58 nm and 91.39 ± 2.34 %, respectively. The distributions of CPT-11 and SN-38 in the tumor after i.v. administration of F-Lip, CPT-11-loaded liposomes (C-Lip), and CPT-11 injection (C-Inj) were far greater with the F-Lip group in comparison to the C-Inj and C-Lip, which might contribute to folate-meditated targeting uptake by the folate receptor on the surface of the tumor cells. The uptake of CPT-11 in the liver and rectum for two liposome groups were all markedly increased as compared to the C-Inj. Moreover, F-Lip exhibited a dose-dependent tumor growth inhibition and superior anticancer activity to C-Lip and C-Inj after i.v. administration. It also showed no significant body weight loss and much lower toxicity on the center immune organs. Therefore, F-Lip may be presented as potential candidates for tumor targeting drug delivery.
Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
Ziqiang
Z
Zhang
Jing
J
Yao
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000138:chemical synthesis; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000008:administration & dosage* / Q000138:chemical synthesis; D000077146:Irinotecan; D008081:Liposomes; D051379:Mice; D008813:Mice, Inbred ICR; D011897:Random Allocation; D051381:Rats; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D000077146:Irinotecan; D005492:Folic Acid; D002166:Camptothecin