Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity.
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.
Hyung Park
Jae
J
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Haweolgog-dong, Sungbook-gu, Seoul 136-791, Republic of Korea.
Kwon
Seunglee
S
Lee
Minsu
M
Chung
Hesson
H
Kim
Ji-Hyun
JH
Kim
Yoo-Shin
YS
Park
Rang-Woon
RW
Kim
In-San
IS
Bong Seo
Sang
S
Kwon
Ick Chan
IC
Young Jeong
Seo
S
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
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; C118638:glycol-chitosan; D004317:Doxorubicin; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate