Mitoxantrone-loaded BSA nanospheres and chitosan nanospheres for local injection against breast cancer and its lymph node metastases. II: Tissue distribution and pharmacodynamics.
Bovine serum albumin (BSA) and chitosan (CS) nanospheres of mitoxantrone (MTO) were comparatively evaluated in terms of tissue distribution, acute toxicity and therapeutic efficiency against breast cancer and its lymph node metastases. After local injection in rats, MTO nanospheres showed a slower elimination rate and a much higher drug concentration in lymph nodes compared with MTO solution, and a lower drug concentration in other tissues. There was no observed acute toxicity to the main tissues of Kunming mice after local injection of MTO-BSA-NS. Mild toxicity to liver and lung was observed for MTO-CS-NS, but, for MTO solution, severe toxicity to liver and lung and much lower number of white blood cells were observed. Human MCF-7 breast cancer in nude mice and animal model of P388 lymph node metastases in Kunming mice were applied to investigate the therapeutic efficiency. The inhibition rate of the nanospheres against breast cancer was much higher than that of MTO solution, and lymph node metastases were efficiently inhibited by the nanospheres, especially MTO-BSA-NS.
Lu
Bin
B
West China School of Pharmacy, Sichuan University, Chengdu 610041, China. lubin@wcums.edu.cn
Xiong
Su-Bin
SB
Yang
Hong
H
Yin
Xiao-Dong
XD
Zhao
Ruo-Bing
RB
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D005260:Female; D006801:Humans; D007267:Injections; D008198:Lymph Nodes / Q000737:chemistry / Q000378:metabolism; D008207:Lymphatic Metastasis; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008942:Mitoxantrone / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D049329:Nanostructures; D009368:Neoplasm Transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute
D000970:Antineoplastic Agents; D012710:Serum Albumin, Bovine; D048271:Chitosan; D008942:Mitoxantrone