Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice

• Published in: Journal of controlled release Vol. 127; no. 1; pp. 41 - 49
• Main Authors: Kim, Jong-Ho, Kim, Yoo-Shin, Park, Kyeongsoon, Lee, Seulki, Nam, Hae Yun, Min, Kyung Hyun, Jo, Hyung Gon, Park, Jae Hyung, Choi, Kuiwon, Jeong, Seo Young, Park, Rang-Woon, Kim, In-San, Kim, Kwangmeyung, Kwon, Ick Chan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07.04.2008; Elsevier
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Biological and medical sciences; Cell Survival - drug effects; Chitosan - chemistry; Chitosan - pharmacokinetics; Cisplatin; Cisplatin - administration & dosage; Cisplatin - chemistry; Cisplatin - pharmacokinetics; Cisplatin - therapeutic use; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug delivery system; General pharmacology; Humans; Hydrophobically modified glycol chitosan; In vivo antitumor efficacy; Male; Medical sciences; Mice; Nanoparticles - chemistry; Particle Size; Passive tumor targeting; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Self-assembled nanoparticles; Solubility; Tissue Distribution; Xenograft Model Antitumor Assays; Hydrophobically modified glycol chitosan; In vivo antitumor efficacy; Self-assembled nanoparticles; Drug delivery system; Cisplatin; Passive tumor targeting; Antineoplastic agent; Targeting; Nanoparticle; Drug carrier; Target; Efficiency; Microparticle; Platinum II Complexes; Pharmaceutical technology; Rodentia; Polymer; Malignant tumor; In vivo; Alkylating agent; Vertebrata; Mammalia; Mouse; Animal; Chitosan; Glycol; Cancer
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2007.12.014

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.