Study Of Effects Of Intratumoral Injection Of 5-fluorouracil-loaded Carbon Nanoparticles Delivery System In Mice Bearing S180 Sarcoma

The nanoparticles of active carbon (10-1000nm in diameter) show excellent Sustained-released property;lymph-targeting property, strong capacity of adsorption into regional lymph nodes and the surface of the turmor ,while low adverse effect .All of these marvellous properties result from that when the diameter of active carbon is in nanometer level, The surface area of the carbon nanoparticles will be increased dramatically,even to1480m2/g, so the capacity of adsorption will increased dramatically as well as their stability. Our research is based on the recent progresses of the preparation and properties in vitro and invivo of the dosage form on the basis of related properties mentioned above. In my work, This kind of activated carbon particles is used as anticancer drug carrier to carry anticancer drug to the regional lymph nodes and turmor . This kind of new Sustained-release dosage form of active carbon can released anticancer drug sowly to obtain the proper drug concentration in the region .So this kind of new Sustained-release dosage has strong capacity to lessen the systemic adverse effect and eveluate therapeutic index. Activated carbon nanoparticles as anticancer drug carrier into regional lymph nodes and turmor displays a promising prospect in the treatment of cancer.There are three part in our research. The first part is to investigate the antitumor effects of 5-fluorouracil-loaded carbon nanoparticle in intratumoral administration to the mice bearing S180 sarcoma and to provide experimental foundation for clinical application.;The second is to observe the concentration of 5-FU and in mice bearing S180 sarcoma at a series of given time points. , To study the pharmacokinetic differences of intratumoral chemotherapy between the 5-fluorouracil-loaded carbonnanoparticles delivery system and 5-Fu in mice bearing SI80 sarcoma ,and set up a pharmacokinetic model for clinical practice . Based on the two parts above ,we set up the mathematic model of intratumoral administration in mice bearing SI80 sarcoma with applied mathematics and software programming, we can simulate the drug delivery regularity of intratumorally administration with the mathematic model, obtain the concentration of drug in blood and the intratumoral concentration at some given dose .so that we can predict the general toxicity and therapeutic efficacy at the given dose, so we can master the proper dose regularity. The concrete methods and result are as follows:Part one: Study of effects of intratumoral injection of 5-fluorouracil-loaded carbon nanoparticle sustained-release preparation on the mice with SI80.In this part, eighty KunMing mice bearing SI80 sarcoma were randomized into eight groups , and individual tumor growth was observed , drug related systemic toxicity was also evaluated before and after administration of 5-fluorouracil-loaded carbon nanoparticle sustained-release preparation, and the specimen were observed under microscope. The results show the tumors volume of intratumoral injection of 5-fluorouracil-loaded carbon nanoparticles sustained-release preparation on the mice bearing SI80 sarcoma increased slower than that of of systemic administration of 5-FU alone and that of intratumoral injection of 5-FU alone ,and exhibited dose-effective relationship.Part two: Pharmacokinetic comparison of intratumoral chemotherapy between the5-fluorouracil-loaded carbon nanoparticles delivery systemand 5-Fu in mice bearing SI 80 sarcomaIn the second part, 136 KunMing mice bearing SI 80 sarcoma were randomized into two groups . The animal were treated with 5-FU—CNP injection and free 5-FUseparately. Then the drug concentration in turmor and blood was examed by high performance liquid chromatography (HPLC) at a series of given time points., and the specimen were observed under microscope. Results The pharmacokinetic parameters in the twogroup ,such as Tmax ,T1/ 2 (ke) and AUC ,were significantly different in statistical analysis. The AUC of the 5-FU-CNP group was much higher than that of 5-FU group ,as well as Tl/ 2 (ke) and Tmax , while the Cmax was slightly lower.Both the intratumoral AUC and Cmax of the 5-FU-CNP group are much higher than those of the 5-FU-CNP group in blood . Conclusion Pharmacokinetic analysis revealed that the 5-fluorouracil-loaded carbon nanoparticles delivery system can prolong the drug action time and enhance the bioavailability of 5-Fluorouracil.Part three : construction of the mathematic model ofintratumoral administration inmice bearing SI 80 sarcomaBased on the two parts above ,we constructed the mathematic model of intratumoral administration in mice bearing SI80 sarcoma with applied mathematics and software programming, we can simulate the drug delivery regularity of intratumorally administration with the mathematic model, obtain the concentration of drug in blood and the intratumoral concentration at some given dose .so that we can predict the general toxicity and therapeutic efficacy at the given dose, so we can master the proper dose regularity .Lastly,we can draw the conclusion :The antitumor effect of intratumoral administration 5-fluorouracil-loaded carbon nanoparticles is better than that of local and systemic administration of 5-FU alone. 5-FU —CNP can be regarded as a potentially effective drug system in the therapy of cancer.