OBJECTIVE To prepare paclitaxel-loaded anionic chitosan micelles (PTX-ACM) and study thebiodistribution of PTX-ACM and Paclitaxel Injection (PTX-INJ) in mice.METHODS PTX-ACM were prepared by dialysis method. PTX-ACM and PTX-INJ were[KG)] administered to mice by tail vein at the dosage of 20 mg·kg-1 body weight. The RP-HPLC method was established to determine the PTX concentrations in plasma and tissues of mice. The in vivo distribution and targeting were evaluated by the pharmacokinetic parameters (AUC, MRT) and targeting parameters (re, Ce and te).RESULTS The drug loading and drug encapsulation efficiency of PTX-ACM were up to 89.90% and 34.59%, respectively, and the diameters and Zeta potential were 179.9 nm and -28.0 mV, respectively. The most high uptake of PTX-ACM and PTX-INJ in liver were 91.84% and 21.99% of dose respectively. In contrast to PTX-INJ group, the AUC of PTX in the liver and spleen had raised 35.61 and 168.74 times as that of PTX-ACM group respectively. Meanwhile, MRT of PTX in liver and spleen were significantly prolonged and were 17.13 and 24.92 fold than that of PTX-INJ respectively. For PTX-ACM, targeting efficiency (te) of liver and spleen were 1 617.69 and 736.85 respectively, while 3.64 and 0.35 were obtained for PTX-INJ respectively. The AUC of PTX in the lung in PTX-ACM group was 93.37% as that of PTX-INJ, while MRT was 3.31 times longer than that of PTX-INJ. In PTX-ACM group, PTX in the heart and kidney were decreased significantly and AUC were 27.21% and 43.43% as that of PTX-INJ respectively, while MRT were 1.44 and 1.17 times longer. ρmax of both tissues were decreased dramatically and were only 38.76% and 19.10% as that of control group. CONCLUSION ACM show excellent drug loading capabilities and have amount of anionic charges on their surface. PTX-ACM show a high liver and spleen targeting efficiency in vivo and can keep high drug levels in both tissues for relatively long time. The biodistribution of PTX in the lung are comparative in both groups while PTX-ACM have a better lung retentive ability. The levels of PTX-ACM in the heart and kidney tissues are significantly reduced which might decrease the side effects.
HUO Mei-rong;ZHOU Jin-ping;WEI Yn;Lü Lin.
Preparation of Paclitaxel-Loaded Cationic Chitosan Polymeric Micelles and Its Tissue Biodistribution in Mice [J]. Chinese Pharmaceutical Journal, 2006, 41(24): 1876-1880
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