title: Synthesis and characterization of the tumor targeting mitoxantrone-insulin conjugate.
abstract: Anticancer drugs have serious side effects arising from their poor malignant cells selectivity. Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at 37 degrees C within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1% of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 microg x h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 microg x h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes (TIC) no larger than 0.3 besides good tumor targeting efficiency with TIC of 1.67. The results suggest the feasibility to promote the curative effect in cancer chemotherapy by using insulin as the vector of anti-cancer drugs.
authors.affiliation: Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051379:Mice; D008942:Mitoxantrone / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D007328:Insulin; D008942:Mitoxantrone