| Colorectal cancer is one of the most common malignant tumors in human beings.The primary treatment is surgical resection.However,since most of the patients are diagnosed at the late stage and are prone to relapse or metastasis after operation,chemotherapy has been recognized as clinical alternative for colorectal cancer treatment.Irinotecan is mainly used to treat advanced cancer patients and patients who have failed with 5-fluorouracil chemotherapy.At present,the commercial irinotecan product is irinotecan hydrochloride injection with low curative effect and high toxicity.By loading irinotecan hydrochloride into phosphatidylethanolamine(DSPE-mPEG2000)based nanomicelles,the nanomicelle injection can enrich irinotecan hydrochloride at tumor by EPR effect,and prolong its retention time in the body,improving the therapeutic effect and lowing the toxicity.However,due to the introduction of medically unapproved composition,it is necessary to study the safety of irinotecan hydrochloride nanomicelles.Among various indicators,in vitro release and endotoxin are two key elements to be tested.Therefore,we studied the in vitro release and endotoxin by using irinotecan hydrochloride nanomicelles.Firstly,dialysis and separation sampling methods were used to test the release profile of irinotecan hydrochloride.Results indicated that these sampling methods were limited by the drug adsorption on dialysis membrane in dialysis sampling method and structural damage of nanomicelles in separation sampling method.Then we further studied gel filtration method.Because of its high repeatability,simplicity and rapidity,it is hopeful to replace the above two methods to study the release of this kind of micelles in vitro.In addition,we tested the endotoxin of irinotecan hydrochloride nanomicelles by the Limulus Amebocyte Lysate assay（LAL）and the Rabbit Pyrogen Test（RPT）.Results showed that nanomaterials interfered with the limulus reagent.And irinotecan hydrochloride itself would low the body temperature of the rabbit.Therefore,it is necessary to develop new method to overcome these issues that may interfere during accurate evaluation of endotoxin due to these limitations of LAL and RPT in testing endotoxin.Our research has guiding significance for the clinical application of nanomedicines and provides a reference for the study of PEG micellar drugs. |
