글리콜 키토산-독소루비신 나노복합체의 생체분포와 항암효과
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Self-assembled nanoparticles, formed by polymeric amphiphiles, have been demonstrated to accumulate in solid tumors bythe 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 for investigating their biodistribution in and anti-tumor activity to the tumor-bearing mice. Biodistribution of self-aggregates (300 nm in diameter) was evaluated using tissues obtained from tumor-bearing mice, to which self-aggregates were systemically administrated 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 increasedin tumor as blood circulation time increased. The concentration of self-aggregates in blood was as high as 10 % of does at one day after intravenous injection and was still higher than 8 % even at three days. From in vivo animal tests, it was evident that the self-aggregates loaded with doxorubicin exhibit 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.