Pharmacokinetics Study Of Intraperitoneal Chemotherapy With Mitomycin C Bound To Activated Carbon Nanopaticles

OBJECTIVE:To analyze the pharmacokinetics of intrapefitoneal chemotherapy with mitomycin C(MMC)bound to Activated Carbon Nanoparticles(ACNP) and prove what advantage does ACNP have than activated carbon particles(CH).METHODS:A nude mouse model with transplanted human gastric cancer was established. The mice were given MMC by i.v. or intraperitoneal (i.P.)injections or given i.p. MMC bound to activated carbon particles (MMC-CH),or given i.p.MMC bound to activated carbon nanopaticles (MMC-ACNP). Pharmacokinetic assays were carried out at different time points(0.5,1,2,3,6,12 and 24 h)in 7 mice per each time point, to measure the MMC concentrations by HPLC and compare them.RESULTS:1. The MMC concentration in lymph nodes, mesentery and peritoneal exudate of both MMC-ACNP and MMC-CH group were significantly higher than that of MMC solution i.p. group and MMC i.v. group(P＜0.01). On the other hand, the MMC level in plasma was significantly lower than that in two control groups(P＜0.01).2. High MMC level was maintained at least 24 hours in the MMC-ACNP and MMC-CH group.The remarkable event is that the MMC concentration of MMC-ACNP group is obviously higher than that of MMC group at every time point in lymph nodes and at two time point(12,24h) in mesentery and peritoneal exudates(P＜0.05).3. Intraperitoneal chemotherapy with MMC solution resulted in a low MMC concentration in plasma, peritoneal exudate and lymph nodes, and only a transient high level of MMC in the mesentery. 4. After i.v. administration, a significantly higher level of MMC concentration occurred in the plasma, but only a shortlv increased concentration of MMC in the mesentery, and lower concentration in peritoneal exudate and lymph nodes as compared with those in the other two groups (P＜0.01).CONCLUSIONS:1. High concentration of MMC in lymph nodes, mesentery and peritoneal exudate maintained at least 24 hours and a significantly lower MMC plasma concentration can be achieved by administration of intraperitoneal administration of MMC bound to both carbon nanoparticles and activated carbon particles.2. Activated carbon nanoparticles is a perfect drug delivery system for lymphatic targeting in preventing metastasis and recurrence than activated carbon particles.