한빛사 논문
Abstract
Jae Hyung Parka, b, Seunglee Kwona, Minsu Leea, Hesson Chunga, Ji-Hyun Kimc, Yoo-Shin Kimc, Rang-Woon Parkc,1, In-San Kimc, Sang Bong Seod, Ick Chan Kwona, Seo Young Jeonga
a Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Haweolgog-dong, Sungbook-gu, Seoul 136-791, Republic of Korea
b Department of Advanced Polymer and Fiber Materials, College of Environment and Applied Chemistry, Kyung Hee University, Gyeonggi-do 449-701, Republic of Korea
c Department of Biochemistry, School of Medicine, Kyungpook National University, 101 Dongin-dong, Jung-gu, Daegu 700-422, Republic of Korea
d JAKWANG Co., Ltd., Ansung, Kyonggi 456-380, Republic of Korea
Corresponding author : Rang-Woon Park, Ick Chan Kwon
1 Also corresponding author
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.
Keywords : Drug delivery; Glycol chitosan; Nanoparticle; Self-assembly
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