Nano-activated Carbon In The Treatment Of Gastric Cancer

Gastric carcinoma is kind of common gastrointestinal malignant tumors. Operation remains to be the most effective treatment all the time. Lymph node metastasis is the key factor that influence the survival time after operation. Classic D2 radical resection has claimed high requirements for perigastric lymph node dissection. Activated carbon nanoparticle (ACNP) is kind of commonly used clinical tracing dyes. It is black and of good lymph-targeted characteristic which can effectively help lymph node dissection. Even for the skilled surgeons, ACNP can help the Sentinel Lymph Node Biopsy(SLNB) that could help avoid excessive lymph node dissection, shorten operational time and decrease the occurrence of postoperative complications. ACNP is also kind of good carrier for drugs. It may assist drugs to reach target tissue with the lowest loss of dose and activity during transportation. Tumor cells are killed selectively. Blood cells and bone marrow cells are kept safe. After ACNP combined with chemotherapeutic drugs is absorbed into capillary lymph tubes, it will not only dye the lymph nodes into black but also slowly release drugs into them to perform as a pharmaceutical lymph node dissection function. At present, ACNP which is authorized by Chinese Drug Administration for clinical use is Carbon Nanoparticle Suspension (CNS) produced by Chongqing LUMMY Pharmaceutical Co., Ltd. Our subject aimed at the value of CNS for the treatment of gastric carcinoma that included five chapters as follows.Chapter 1. The preparation and research of Carbon Nanoparticle Paclitaxel SuspensionObjective:To search a kind of chemotherapeutic drug that can be absorbed by CNS well and test their Saturated Absorption Capacity (SAC).Materials and method:We had chosen oxaliplatin and paclitaxel to combine with CNS separately to form suspension that could be used in lymphatic chemotherapy for gastric carcinoma. With the assistance of Chongqing LUMMY Pharmaceutical Co., Ltd, we tested the SAC of Carbon Nanoparticle Paclitaxel Suspension(CNPS) by High Performance Liquid Chromatography.Result:Since there was physiological saline in CNS and oxaliplatin would break down after meeting chlorine ion, oxaliplatin was abandoned. By comparison, paclitaxel could be absorbed by CNS easily. We had declared patents for it.Conclusion:CNPS had stable physical and chemical properties. The SAC of CNS absorbing paclitaxel was lml of CNS to 7mg of paclitaxel.Chapter 2. Research about the security of gastric subserosal injection with CNPSObjective:To research the security of gastric subserosal injection with CNPS during gastrectomy.Materials and methods:We divided SPF Wistar rats into 2 groups. They were given subserosal injection with CNS or NS separately after which they both received gastrectomy. We observed the side effects in 7 days after operation.Result:In the experimental group, one rat died of respiratory failure during operation. One rat died of anastomotic leakage.7 rats of the survival had intraperitoneal adhesion 7days later. In the control group, one rat died of respiratory failure during operation. One rat died of anastomotic leakage. One rat died of intraperitoneal active bleeding.6 rats of the survival had intraperitoneal adhesion 7days later.Conclusion:There were no statistical differences in mortality, rates of anastomotic leakage and abdominal adhesions between the 2 groups. Gastric subserosal injection with CNPS was safe.Chapter 3. Observation and improvement for lymph node tracing effect of subserosal injection with CNSObjective:To observe the lymph node tracing effect of gastric subserosal injection with CNS and make improvements.Materials and methods:At first, we did lymph node tracing by subserosal injection with CNPS on pigs. Then we had chosen 2 clinical patients who suffered from gastric carcinoma to receive lymph node tracing with CNS through subserosal injection during operation. At last, we designed further experiments to improve the lymph node tracing method by intraperitoneal injection with CNS on Wistar rats. Result:The lymph node tracing effect of subserosal injection with CNS on pigs, patients and rats all turned out to be unsatisfying. By contrast, 3 days after intraperitoneal injection, far better lymph tracing effect could be obtained.7 days after intraperitoneal injection, tracing effect remained more clear and with less contamination.Conclusion:The lymph node tracing effect of subserosal injection with CNS on pigs, patients and rats all turned out to be unsatisfying that could not meet the demands of D2 radical resection and SLNB. Intraperitoneal injection with CNS could gain better tracing effect. It may be promising.Chapter 4. Research about modeling for SPF-grade rats/mice carrying tumors with metastatic lymph nodesObjective:To model SPF-grade rats or mice carrying tumors with metastatic lymph nodes.Materials and methods:We had tried EL-4 strains of lymphoma by intraperitoneal injection to SPF-grade C57BL mice, CT-26 strains of colon carcinoma by injection under foot pad to SPF-grade BALBC mice and Walker-256 strains of ascites tumor by orthotopic transplantation to SPF-grade wistar rats. Later we observed the formation of tumors to see whether there were tumors with metastatic lymph nodes.Result:1-2 weeks after intraperitoneal injection with EL-4 strains, diffused abdominal tumors could be obtained. No lymphatic metastasis happened 1 month later.1 week after injection under foot pad with CT-26 strains, local lesion could be obtained. No lymphatic metastasis happened 2 months later. Tumors stopped growing after 12 weeks of growth age in Wistar rats carrying walker-256 strains.Conclusion:Usage of EL-4 strains of lymphoma by intraperitoneal injection to SPF-grade C57BL mice, CT-26 strains of colon carcinoma by injection under foot pad to SPF-grade BALBC mice and Walker-256 strains of ascites tumor by orthotopic transplantation to SPF-grade wistar rats could not form models carrying tumors with metastatic lymph nodes.Chapter 5. Study about the pharmacokinetics of intraperitoneal chemotherapy with CNPS Objective:To study the pharmacokinetics of intraperitoneal chemotherapy with CNPSMaterials and methods:We randomly threw Wistar rats into the experimental group (A) and the control group(B), to which intraperitoneal injections of CNPS and paclitaxel were given respectively. At different time points, we got the samples of the rats' blood, mesenteric lymph nodes and intraperitoneal washing fluid to test and analyze the concentration of paclitaxel.Results:The ratio of AUC in plasma of group A to group B was 0.6263. The ratio of AUC in lymph nodes of group A to group B was 0.7495 and that in intraperitoneal washing fluid was 1.25. The metabolic half-life of paclitaxel (t1/2) in plasma of group A was 1.607 times as long as that of group B. The t1/2 of paclitaxel in intraperitoneal washing fluid of group A was 0.879 as long as that of Group B. The t1/2 of paclitaxel in lymph nodes of group A was 1.097 as long as that of Group B.Conclusion:Intraperitoneal chemotherapy by CNPS was characterized by low drug concentration in blood, high drug concentration in peritoneal and high security, but lack of significant lymph targeting and lymphatic retention effect. The mechanism remained to be studied further.