| OBJECTIVE: To study the development and research of CBMC that is ANTC adsorbed by NPC. METHODS: The size of targeting carrier(NPC) was characterized by NPC; Adsorption features of NPC for ANTC was investigated by uLtraviolet spectrophotometer; Design and prepare the CBMC, the drug loading of which was specified, according to the resuLts of adsorption features of NPC; The release characteristics of CBMC was studied by HPLC; The LD50 of NPC, ANTC and CBMC was determined and compared; The anti-cancer effect of CBMC was studied by MTT; Then measured the dose-effect relationship and calcuLated the IC50 based on the MTT resuLts. The anti-cancer action of CBMC in vivo was studied by observing its effect on the animal tumor model. Meanwhile, the guiding effect of the CBMC to NPC is observed by conventional dye and TEM. The cell cycle was distinguished by PI staining was detected flow cytometer in order to explore the synergistic action of NPC for anti-cancer drugs. The peritoneal and plasma distribution in rats was studied by HPLC, then the corresponding pharmacokinetic parameters based on the time process of blood drug concentration were calcuLated.RESULTS:1. The average particle size was 319±111 nm for NPC.2. NPC can absorb ANTC effectively and the absorption curve is consistent with exponential form 172*C0.145(R=0.953,P<0.0001) at 25℃. Reached equilibrium time of NPC for ANTC was about 0.5h, which was unrelated to the mass ratio of NPC to ANTC. The quantity of ANTC adsorbed by Per unit mass NPC was 285mg/g.3. The production formuLa of CBMC was established according to the adsorption features of NPC for ANTC. 3 batches, totally 954 branches, CBMC injection was obtained by middle test.4. LD50 of mice received intraperitoneal injection of NPC was more than 4000mg/kg. LD50 of mice received intravenous injection of NPC was about 308.52mg/kg. LD50 of mice received intraperitoneal and intravenous injections of NPC were 5.83 and 4.97mg/kg. LD50 of mice received intraperitoneal injection of CBMC was about 122.91mg/kg. Toxicity of CBMC was 3.5 times that of ANTC.5. CBMC exhibits advanced function of anticancer, which displays better dose-effect relationship. The inhibitory concentration 50%(IC50) of CBMC in BGC-823, HepG-2, 7701, H460, H1299 and JF305 were 41.8, 31.4, 97.08, 256.14, 129.13 and 58.60μg/ mL, respectively.6. In vivo CBMC can inhibit the growth of solid tumor in and prolong the life span of ascetic tumor mice. CBMC exhibits advanced function of anticancer, which displays better dose-effect relationship; CBMC with the better postponed life property and the inhibition the growth of tumor shows much higher than the dissociated MMC with equivalent quantities. The resuLts suggest that ANTC can stay on the local or can been guided to tumor tissues because of carrier effect of NPC, then high-concentration was formed at the local and ANTC was released.7. The resuLts of pathological section and TEM showed that NPC can adhere on and entere into tumor tissues. Then, NPC can enter into tumor cells. The target molecuLes of NPC were cell nuclear, mitochondria and lysosome.8. In vitro high dose of NPC can block the BGC-823 cell cycle in S phase which suggested that he synergistic action of NPC for anti-cancer drugs.9. HPLC of CBMC in rats was established. Then the corresponding pharmacokinetic parameters were calcuLated. The resuLts showed that CBMC was eliminated slower, blood drug concentration lower and selectivity better than that of rats received intraperitoneal injection. The tissue drug concentration of ANTC in great epiploon, stomach , peritoneum, diaphragmatic and lymph was high than that of other tissues.
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