DNA/chitosan nanocomplex as a novel drug carrier for doxorubicin.
The present study was to investigate the potentials of DNA/chitosan nanocomplexes as a carrier for small drug delivery. Two highly water-soluble chitosans (87 kDa and 18 kDa) were prepared and labeled with fluorescein isothiocyanate (FITC). DNA/chitosan nanocomplexes were prepared by mixing salmon testes DNA and the FITC labeled chitosan (FITC-chitosan) and their biophysical properties and biodistribution in vivo were then investigated. The molecular weight of chitosan and the ratio of the positive amino group of chitosan to the negative phosphate group of DNA (N/P ratio) influenced the physical properties of the nanocomplexes. The fluorescence intensity of both types of the free FITC-chitosan decreased rapidly within 4 hr post-injection. In contrast, the DNA/chitosan nanocomplexes were accumulated in the liver and kidneys and remained at a relatively high stable level in these tissues and in blood up to 24 hr post-injection. This study also assessed the stability of the anti-cancer drug doxorubicin (DOX) when it was conjugated to chitosan to form a chitosan-doxorubicin conjugate (chi-DOX), which was then mixed with DNA to form a DNA/chitosan-doxorubicin nanocomplex (DNA/chi-DOX). Both the chi-DOX and DNA/chi-DOX complexes exerted cytotoxic effects on HeLa, HepG2, QGY-7703, and L02 cells, while the non-malignant L02 cells were less sensitive to the DNA-containing complex than to the chi-DOX complex, suggesting possible selectivity. Studies in tumor-bearing animals demonstrated that DNA/chi-DOX could efficiently deliver doxorubicin to the tumor and liver, implying that the DNA/chitosan nanocomplex may represent a novel drug carrier.
Cheng
Xiaoyun
X
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
Zhang
Feng
F
Zhou
Guangxin
G
Gao
Shuying
S
Dong
Lei
L
Jiang
Wei
W
Ding
Zhi
Z
Chen
Jiangning
J
Zhang
Junfeng
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D048271:Chitosan / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D019793:Fluorescein; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D049329:Nanostructures; D012995:Solubility; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004337:Drug Carriers; D004317:Doxorubicin; D004247:DNA; D048271:Chitosan; D019793:Fluorescein