title: Characterization of 9-nitrocamptothecin-in-cyclodextrin-in-liposomes modified with transferrin for the treating of tumor.
abstract: Encapsulation of hydrophobic drugs in the form of drug-cyclodextrin (CD) complex in liposomes has been applied as a novel strategy to combine the relative advantages of CDs and liposomes into one system, naming drug-in-CD-in-liposome (DCL). In the present study, soluble 9-NC/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes were prepared using the freeze-drying technique. Then 9-NC inclusion complexes were further encapsulated into liposomes by ethanol injection method and transferrin (Tf) was conjugated to the surface of 9-NC DCL to obtain Tf modified 9-NC DCL (Tf-9-NC-CL). Compared to PEGylated 9-NC DCL (P-9-NC-CL), the lactone stability and vesicle stability of Tf-9-NC-CL were significantly increased. Both 9-NC and HP-β-CD were found to release from the DCL and Tf modification resulted in reduced release of them. The enhanced targeting efficiency of the Tf-modified liposomes was demonstrated by flow cytometry and confocal microscopy. In vivo pharmacokinetics in rats showed improved lactone stability of 9-NC following intravenous injection of Tf-9-NC-CL. The cytotoxicity of Tf-9-NC-CL against tumor cells and normal cells was investigated in vitro and the antitumor efficacy was evaluated in S180 tumor-bearing mice in vivo. Compared with free 9-NC, 9-NC inclusion complexes and P-9-NC-CL, Tf-9-NC-CL demonstrated the strongest cytotoxicity to tumor cells. And the inhibitory rate of tumor (IRT) values were determined to be 43.08%, 56.92%, 67.69% and 80.00% for 9-NC solution, inclusion complexes, P-9-NC-CL and Tf-9-NC-CL, respectively. In conclusion, Tf modification can be useful in increasing vesicle stability, targeting drug delivery efficiency and antitumor efficacy of DCL containing hydrophobic antitumor drugs, such as 9-NC.
authors.affiliation: Pharmaceutical Research Laboratory, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: chenjun75@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Pharmaceutical Research Laboratory, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Pharmaceutical Research Laboratory, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Hubei Collaborative Innovation Center of Targeted Antitumor Drug, Jingchu University of Technology, Jingmen 448000, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Peng
authors.affiliation: Pharmaceutical Research Laboratory, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Dong
authors.affiliation: Pharmaceutical Research Laboratory, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Hubei Collaborative Innovation Center of Targeted Antitumor Drug, Jingchu University of Technology, Jingmen 448000, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Hubei Collaborative Innovation Center of Targeted Antitumor Drug, Jingchu University of Technology, Jingmen 448000, China.
authors.forename: Zheyun
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Hubei Collaborative Innovation Center of Targeted Antitumor Drug, Jingchu University of Technology, Jingmen 448000, China. Electronic address: yxixiong@163.com.
authors.forename: Xixiong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D007783:Lactones / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D009369:Neoplasms / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014168:Transferrin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003505:Cyclodextrins; D004337:Drug Carriers; D007783:Lactones; D008081:Liposomes; D014168:Transferrin; C079905:rubitecan; D002166:Camptothecin
keywords: 9-Nitrocamptothecin; 9-Nitrocamptothecin (CID: 472335); Antitumor efficacy; Coumarin-6 (CID: 100334); Cyclodextrin; Liposomes; Stability; Transferrin modification