title: Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice.
abstract: To make a tumor targeting nano-sized drug delivery system, biocompatible and biodegradable glycol chitosan (M(w)=250 kDa) was modified with hydrophobic cholanic acid. The resulting hydrophobically modified glycol chitosans (HGCs) that formed nano-sized self-aggregates in an aqueous medium were investigated as an anticancer drug carrier in cancer treatment. Insoluble anticancer drug, cisplatin (CDDP), was easily encapsulated into the hydrophobic cores of HGC nanoparticles by a dialysis method, wherein the drug loading efficiency was about 80%. The CCDP-encapsulated HGC (CDDP-HGC) nanoparticles were well-dispersed in aqueous media and they formed a nanoparticles structure with a mean diameter about 300-500 nm. As a nano-sized drug carrier, the CDDP-HGC nanoparticles released the drug in a sustained manner for a week and they were also less cytotoxic than was free CDDP, probably because of sustained release of CDDP from the HGC nanoparticles. The tumor targeting ability of CDDP-HGC nanoparticles was confirmed by in vivo live animal imaging with near-infrared fluorescence Cy5.5-labeled CDDP-HGC nanoparticles. It was observed that CDDP-HGC nanoparticles were successfully accumulated by tumor tissues in tumor-bearing mice, because of the prolonged circulation and enhanced permeability and retention (EPR) effect of CDDP-HGC nanoparticles in tumor-bearing mice. As expected, the CDDP-HGC nanoparticles showed higher antitumor efficacy and lower toxicity compared to free CDDP, as shown by changes in tumor volumes, body weights, and survival rates, as well as by immunohistological TUNEL assay data. Collectively, the present results indicate that HGC nanoparticles are a promising carrier for the anticancer drug CDDP.
authors.affiliation: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Yoo-Shin
authors.initials: YS
authors.lastname: Kim
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Hae Yun
authors.initials: HY
authors.lastname: Nam
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Min
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Jo
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C118638:glycol-chitosan; D048271:Chitosan; D002945:Cisplatin