ABSTRACT
Objective:Considering the efficacy of Gegen Qinliantang （GQT） in releasing exterior and clearing interior to alleviate dampness-heat dysentery， we analyzed the mechanism of the chloroform extract of GQT in alleviating enterotoxicity caused by irinotecan to provide an experimental basis for the development of GQT. Method:Kunming mice （<italic>n</italic>=60） were randomly divided into a blank group， a model group， a loperamide group （positive drug of loperamide hydrochloride capsule， 0.4 mg·kg<sup>-1</sup>）， and high- （2.3 g·kg<sup>-1</sup>） and low-dose （1.16 g·kg<sup>-1</sup>） GQT chloroform extract groups. The mouse model of delayed diarrhea was established by intraperitoneal injection of irinotecan hydrochloride （CPT-11， 55 mg·kg<sup>-1</sup>） for four consecutive days， meanwhile， the mice in the blank group only received the same volume of normal saline. Corresponding drugs were administered by gavage on the fifth day， respectively， while the ones in the blank group and model group were given distilled water for five consecutive days. The general condition of mice in each group was observed， and diarrhea indexes of mice were recorded. Pathological changes in colon tissues of mice were observed by hematoxylin-eosin （HE） staining. The tumor necrosis factor （TNF）-<italic>α</italic>， interleukin （IL）-1<italic>β</italic>， cyclooxygenase （COX）-2， intercellular adhesion molecule （ICAM）-1， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， malondialdehyde （MDA） and nitric oxide （NO） levels in colon tissues were detected with the assay kits. Furthermore， the expression levels of Kelch sample epoxy chloropropane associated protein 1 （Keap1）， nuclear factor E<sub>2</sub> related factor 2 （Nrf2）， tight junction protein-1 （ZO-1）， heme oxygenase-1 （HO-1） and tight junction protein （Occludin） were detected by Western blot. Result:Compared with the blank group， the model group showed declined body weight and reduced contents of GSH-Px and SOD （<italic>P</italic><0.01）， whereas increased diarrhea indexes and TNF-<italic>α</italic>， IL-1<italic>β</italic>， COX-2， ICAM-1， MDA and NO levels （<italic>P</italic><0.01）. Abundant inflammatory cells and colonic mucosa with defects， swelling， bleeding， and inflammatory exudation were revealed by HE staining in the mice of the model group. The expression levels of Keap1， Nrf2， ZO-1， HO-1 and Occludin in colon tissues significantly declined （<italic>P</italic><0.01）. Compared with the model group， the loperamide group and the high- and low-dose GQT chloroform extract groups exhibited improved weight loss， reduced diarrhea indexes， diminished TNF-<italic>α</italic>，<italic> </italic>IL-1<italic>β</italic>， COX-2， ICAM-1， MDA and NO， and elevated GSH-Px and SOD. HE staining indicated that the cells were compactly arranged with clear nuclei in the high- and low-dose GQT chloroform extract groups， and the expression levels of Keap1， Nrf2， HO-1， Occludin， and ZO-1 were up-regulated. Conclusion:GQT chloroform extract may alleviate CPT-11-induced delayed diarrhea by regulating inflammation and oxidative stress for enhancing the intestinal barrier function. These findings are expected to provide a reference for exploring the toxicity-attenuating effect of Chinese medicinals on chemotherapy drugs and for developing famous classical formulas.
ABSTRACT
HPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection. HPLC-RID: This method was performed on a Kromasil 100-5-NH2 column (250 mm×4.6 mm, 5 μm) with a mobile phase of 0.8 mol·L-1 ammonium sulfate buffer (pH 3.5)-acetonitrile (83∶17). The flow rate, column temperature and detector temperature were maintained at 1 mL·min-1, 30 ℃ and 30 ℃ respectively. HPIC-CD: This method was performed on an anion exchange column Dionex InPacTM AS11-HC (250 mm×4 mm, 9 μm) with an eluent of 30 mmol·L-1 sodium hydroxide solution. The flow rate was 1.5 mL·min-1, the column temperature was 30 ℃ and the detector temperature was 35 ℃. The HPLC-RID method and HPIC-CD method were validated with respects to specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, stability and robustness and met the validation requirements. There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis, both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection. However, the HPLC-CD was better at the following aspects: higher detection sensitivity, simpler sample pretreatment, lower time and money spent, better environmental protection.
ABSTRACT
OBJECTIVE: To prepare micelle drug delivery system of irinotecan hydrochloride, which could reduce its side effects and improve the therapeutic effects. METHODS: Firstly, the irinotecan hydrochloride was prepared as phospholipid compound to improve the lipophilicity. The synthesized polycaprolactone-polyethylene glycol copolymer was used as carrier material, then the phospholipid complex of irinotecan hydrochloride was wrapped to prepare a polymer micelle drug delivery system. The optimum prescription and preparation process of micelle drug delivery system of irinotecan hydrochloride were screened by the method of single factor combined with orthogonal test. RESULTS: The liposoluble of phospholipid compound of irinotecan hydrochloride was obviously increased compared with active compound. The irinotecan hydrochloride micelle was spherical and its particle size distribution was uniform. The average entrapment efficiency was 61.32%, and the average drug loading was 2.88%. CONCLUSION: Through this method, the particle size of irinotecan hydrochloride is small and the quality is controllable, and it is hopeful to increase the drug concentration at the target site.
ABSTRACT
Objective To investigate the effect of irinotecan hydrochloride combined with cisplatin on B-cell lymphoma-2 (Bcl-2) and metastasis-associated in colon cancer-1 (MACC1) protein expressions in cervical epithelial tissue of cervical cancer patients.Methods 100 patients with cervical cancer from January 2010 to January 2013 in Department of Obstetrics and Gynecology of Shangrao City People's Hospital were selected as objects.All patients were treated with irinotecan hydrochloride and cisplatin for combination chemotherapy.The clinical effect and the protein expressions of Bcl-2 and MACC1 of cervical epithelial tissue were compared pre-and post-chemotherapy.Results The total efficiency was 75.0%(75/100) after cervical cancer patients were given irinotecan hydrochloride combined with cisplatin chemotherapy program.The expressions and high expression rates of Bcl-2 and MACC1 post-chemotherapy were significantly lower than that pre-chemotherapy(P<0.05) .In clinically effective group, the high expression rates of Bcl-2 and MACC1 post-chemotherapy significantly reduced than pre-treatment (P<0.05), and in clinical invalid group, the difference of the high expression rates of Bcl-2 and MACC1 had no statistically significant.Conclusion After combination chemotherapy with irinotecan hydrochloride and cisplatin on cervical cancer, the expression of Bcl-2 and MACC1 in cervical epithelial tissue significantly reduce, and the clinical efficacy is aignificant.
ABSTRACT
OBJECTIVE:To prepare irinotecan hydrochloride liposome and study its drug release profile in vitro.METHODS:Irinotecan hydrochloride liposome was prepared by ammonium sulfate gradient method.Orthogonal test was conducted to optimize the formula and preparation techniques of irinotecan hydrochloride liposome,and the release of it in vitro was investigated by dialysis method.RESULTS:The entrapment efficiency(EE) of the prepared liposome was as high as 75.4%.The optimized formula was as follows:the ratio of lipid to cholesterol was 2∶1;the concentrations of ammonium sulfate was 0.20 mol?mL-1;the incubation temperature was 50 ℃ and the ratio of drug to lipid was 1∶10.The study proved that the liposome could retard drug release in vitro,at a release rate of 8.09% at 1 h and 64.2% at 9 h.CONCLUSION:The irinotecan hydrochloride liposome had high EE and characterized by slow drug release.