title: Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity.
abstract: Self-assembled nanoparticles, formed by polymeric amphiphiles, have been demonstrated to accumulate in solid tumors by the enhanced permeability and retention effect, following intravenous administration. In this study, hydrophobically modified glycol chitosans capable of forming nano-sized self-aggregates were prepared by chemical conjugation of fluorescein isothiocyanate or doxorubicin to the backbone of glycol chitosan. Biodistribution of self-aggregates (300 nm in diameter) was evaluated using tissues obtained from tumor-bearing mice, to which self-aggregates were systemically administered via the tail vein. Irrespective of the dose, a negligible quantity of self-aggregates was found in heart and lung, whereas a small amount (3.6-3.8% of dose) was detected in liver for 3 days after intravenous injection of self-aggregates. The distributed amount of self-aggregates gradually increased in tumor as blood circulation time increased. The concentration of self-aggregates in blood was as high as 14% of dose at 1 day after intravenous injection and was still higher than 8% even at 3 days. When self-aggregates loaded with doxorubicin were administered into the tumor-bearing mice via the tail vein, they exhibited lower toxicity than but comparable anti-tumor activity to free doxorubicin. These results revealed the promising potential of self-aggregates on the basis of glycol chitosan as a carrier for hydrophobic anti-tumor agents.
authors: Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Haweolgog-dong, Sungbook-gu, Seoul 136-791, Republic of Korea.
authors: Jae
authors: J
authors: Hyung Park
authors: Seunglee
authors: S
authors: Kwon
authors: Minsu
authors: M
authors: Lee
authors: Hesson
authors: H
authors: Chung
authors: Ji-Hyun
authors: JH
authors: Kim
authors: Yoo-Shin
authors: YS
authors: Kim
authors: Rang-Woon
authors: RW
authors: Park
authors: In-San
authors: IS
authors: Kim
authors: Sang
authors: S
authors: Bong Seo
authors: Ick Chan
authors: IC
authors: Kwon
authors: Seo
authors: S
authors: Young Jeong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry; D001835:Body Weight; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry*; D009368:Neoplasm Transplantation; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; C118638:glycol-chitosan; D004317:Doxorubicin; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate