title: Hydroxyethyl starch conjugates for improving the stability, pharmacokinetic behavior and antitumor activity of 10-hydroxy camptothecin.
abstract: 10-Hydroxy camptothecin (10-HCPT)-hydroxyethyl starch (HES) conjugates were prepared to improve the water solubility, prolong the half-life in plasma and increase the antitumor efficacy of 10-HCPT, and the structures of the conjugates were confirmed by NMR and infrared spectroscopy. The 10-HCPT conjugates showed good sustained release effect in phosphate-buffered saline (PBS), rat plasma and liver homogenate. Meanwhile, 10-HCPT-HES conjugates achieved much lower IC50 and higher cytotoxicity effects than the free 10-HCPT on Hep-3B and SMMC-7721 cell lines. The pharmacokinetics results of 10-HCPT-HES conjugates demonstrated that the biological half-life of 10-HCPT was increased from 10 min to 2.94 h and 3.76 h, respectively, in comparison with the commercial 10-HCPT injection. The pharmacodynamics results indicated that 10-HCPT-HES conjugate had a better antitumor efficiency against nude mouse with Hep-3B tumor than the commercial 10-HCPT injection, and the inhibition ratio of tumor was 78.3% and 31.5%, respectively, at the dose of 1.0 mg/kg. These findings suggest that 10-HCPT-HES conjugate is a promising drug delivery system providing improved long circulating effect, greater stability and better antitumor effect.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Guofei
authors.initials: G
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Materials Science and Engineering, Xi' an Jiaotong University, Xi' an 710049, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yin
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: bbparmcai@sina.com.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: tanglab@126.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004355:Drug Stability; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry*; D008297:Male; D008819:Mice, Nude; D015394:Molecular Structure; D017208:Rats, Wistar; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D006895:Hydroxyethyl Starch Derivatives; C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: 10-Hydroxy camptothecin; Antitumor efficacy; Conjugates; Cytotoxicity; Hydroxyethyl starch; Pharmacokinetics