The Pharmacokinetic Mathematical Model Study Of Doxorubicin In Situ Gel In The Tumor Of Colorectal Cancer

Cancer is one of the most dangerous diseases and a great threat to human life.Colorectal cancer (CRC) is one of the most frequent cancers worldwide and is a leadingcause of cancer mortality. Because of the special microenvironment in the malignant solidtumors, the antitumor drugs can’t achieve ideal curative effect. In order to improve theantitumor effects, it needs to increase the blood concentration and period of medication,however, this will produce serious cardiotoxicity. Interstitial chemotherapy is the deliverysystem of antitumor drug that is imbedded to the target tissue, para-tumor, tissue afterremoving the tumor, with many advantages including high efficiency, long-term efficiency,the reducation of dosage and cardiotoxicity.In this paper, the Tumor homograft model was successfully built for the study ofinterstitial chemotherapy. DOX-loaded zein in situ gel was introduced in this study, whichutilized natural protein-Zein with biocompatible and biodegradable as carrier material.The results of the antitumor activity in vitro were significantly enhanced compared withthe DOX group. DOX was sustain released from the in situ gel. It is higher efficientaccumulation of DOX in the tumor and lower drug concentration in blood and normalorgans, which resulted in effective inhibition of tumor growth and fewer off-target sideeffects.In the study, to achieve the development of personalized medicine in interstitialchemotherapy three difficult points have been resolved. Firstly, local drug concentrationwas tested via the confocal laser scanning microscopy technique. Secondly, free drug wastested using microdialysis sampling technique and the confocal laser scanning microscopytechnique. Then the pharma-cokinetic mathematical model of doxorubicin in situ gel inthe tumor was established by matlab (R2008a) software. Thirdly, the thresholdconcentration was obtained by means of studying the starting drug concentration. Theneffective radius was figured out. In conclusion, this study has developed the personalizedmedicine in interstitial chemotherapy, and laid the groundwork for such drug deliverysystem in the clinical application.