[Preparation of paclitaxel-loaded chitosan polymeric micelles and influence of surface charges on their tissue biodistribution in mice].
OBJECTIVE
To prepare paclitaxel-loaded cationic chitosan micelles (PTX-CCM) and paclitaxel-loaded anionic chitosan micelles (PTX-ACM) and study the influence of surface charges on the biodistribution of paclitaxel-loaded chitosan polymeric micelles in mice.


METHODS
PTX-CCM and PTX-ACM were prepared by dialysis method and were administered to mice by caudal vein at a dose of 20 mg x kg(-1) body weight. The RP-HPLC method was established to determine the PTX concentrations in the plasma and other tissues of mice. The tissues distribution of PTX-CCM and PTX-ACM were evaluated by the pharmacokinetic parameters (AUC, MRT).


RESULTS
The diameter and zeta potential of PTX-CCM were 164 nm and +23.7 mV, while those of PTX-ACM were 180 nm and -28.0 mV, respectively. The drug loading and drug encapsulation efficiency for PTX-CCM were 26.4% (w/w) and 76.2% , while those of PTX-ACM were 34.6% (w/w) and 89.9%, respectively. The highest uptake of PTX-CCM and PTX-ACM in liver were 64.72% and 91.84% of dose, respectively. Meanwhile, MRT of both were 5.50 h and 51.39 h prolonged. The highest uptake of PTX-CCM and PTX-ACM in spleen were 7.08% and 5.16% of dose, respectively. Meanwhile, MRT of both were 9.04 h and 26.82 h. For PTX-CCM group, the AUC and C(max) of PTX in the lung were 2.71 times and 5.87 times of those of PTX-ACM group respectively. While in both PTX-CCM and PTX-ACM groups, the highest uptake of PTX in the heart were only 0.36% and 0.24% of dose, respectively and PTX in the kidney were only 0.75% and 0.33% of dose respectively.


CONCLUSIONS
PTX-CCM and PTX-ACM showed excellent drug loading capabilities with amount of cationic charges and anionic charges on their surface, respectively. Both PTX-CCM and PTX-ACM groups showed a higher targeting efficiency in the liver and spleen in vivo and accumulated in both tissues for relatively long time, especially in PTX-ACM group. In contrast to PTX-ACM, PTX-CCM showed a higher lung targeting efficiency in vivo while PTX-ACM had a stronger retention ability in the lung. Meanwhile in both groups the levels of PTX in the heart and kidney tissues were significantly lower which might decrease the side effects of PTX.
Huo
Mei-rong
MR
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Zhou
Jian-ping
JP
Wei
Yan
Y
Lü
Lin
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005260:Female; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D013154:Spleen / Q000378:metabolism; D013499:Surface Properties; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D008823:Micelles; D048271:Chitosan; D017239:Paclitaxel