Anti-tumor activity of N-trimethyl chitosan-encapsulated camptothecin in a mouse melanoma model.
BACKGROUND
Camptothecin (CPT) has recently attracted increasing attention as a promising anticancer agent for a variety of tumors. But the clinical application is largely hampered by its extreme water insolubility and unpredictable side effect. It is essential to establish an efficient and safe protocol for the administration of CPT versus melanoma.


METHODS
Camptothecin was encapsulated with N-trimethyl chitosan (CPT-TMC) through microprecipitation and sonication. Its inhibition effect on B16-F10 cell proliferation and induction of apoptosis was evaluated by MTT assay and flow cytometric analysis in vitro. The anti-tumor activity of CPT-TMC was evaluated in C57BL/6 mice bearing B16-F10 melanoma. Tumor volume, tumor weight and survival time were recorded. Assessment of apoptotic cells within tumor tissue was performed by TUNEL assay. Antiangiogenesis and antiproliferation effects of CPT-TMC in vivo were conducted via CD31 and PCNA immunohistochemistry, respectively.


RESULTS
CPT-TMC efficiently inhibited B16-F10 cells proliferation and increased apoptosis in vitro. Experiment group showed significant inhibition compared with free CPT-treated group (81.3% vs. 56.9%) in the growth of B16-F10 melanoma xenografts and prolonged the survival time of the treated mice (P < 0.05). Decreased cell proliferation, increased tumor apoptosis as well as a reduction in angiogenesis were observed.


CONCLUSIONS
Our data suggest that N-trimethyl chitosan-encapsulated camptothecin is superior to free CPT by overcoming its insolubility and finally raises the potential of its application in melanoma therapy.
Liu
Xian-Ping
XP
Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, China.
Zhou
Sheng-Tao
ST
Li
Xing-Yi
XY
Chen
Xian-Cheng
XC
Zhao
Xia
X
Qian
Zhi-Yong
ZY
Zhou
Li-Na
LN
Li
Zhi-Yong
ZY
Wang
Yu-Mei
YM
Zhong
Qian
Q
Yi
Tao
T
Li
Zheng-Yu
ZY
He
Xiang
X
Wei
Yu-Quan
YQ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D048271:Chitosan / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D005260:Female; D007124:Immunoenzyme Techniques; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012995:Solubility; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D048271:Chitosan; D002166:Camptothecin