30%嘧酶胺悬浮剂的研究

采用湿式超微粉碎加工工艺,对30%嘧酶胺悬浮剂中润湿分散剂、增稠剂、防冻剂、消泡剂及制剂pH值等进行了筛选试验,确定了优惠配方。结果表明,选用嘧酶胺30%、NNO 2%、拉开粉1.5%、农乳33#4%、农乳500#2%、吐温80 2%、凹凸棒土2%作为分散剂,以0.15%黄原胶作为增稠剂,以8%的乙醇作为防冻剂,以硅酮类作为消泡剂所制得的制剂经低温和热稳定性试验,外观无明显分层,水中分散性良好,各项指标均符合悬浮剂的相关标准。

In situ transduction of cytosine deaminase gene followed by systemic use of 5-fluorocytosine inhibits tumor growth and metastasis in orthotopic prostate cancer mouse models

OBJECTIVE: To investigate the antitumor and anti-metastatic effect of in situ transduction of adenovirus encoding cytosine deaminase (AdCD) followed by the systemic use of 5-fluorocytosine (5-FC) in the orthotopic (o.t.) prostate cancer mouse model. METHODS: The o.t. prostate cancer model of C57BL/6 mouse was developed by o.t. inoculation of RM-1 cells to the subcapsular area of the prostate gland. In situ transduction of the CD gene, followed by systemic use of 5-FC at a daily dosage of 300 mg/kg for 14 days, was performed two days later. RESULTS: Compared with mice treated with Adbeta-gal/5-FC, 5-FC and PBS, mice of the o.t. model receiving in situ treatment of AdCD/5-FC had significant prolongation of survival and suppression of local tumor growth. More importantly, pathological observations showed that metastatic activity occurred in all mice of the PBS, 5-FC and Adbeta-gal groups including metastasis to the iliac lymph node (10/10, 10/10, 10/10) and the lung (8/10, 7/10, 7/10). However, only two out of ten had iliac lymphatic metastasis in the AdCD/5-FC group with no systemic or preaotic lymphatic metastasis, suggesting a strong metastatic inhibitory effect. CONCLUSIONS: In situ transduction of AdCD followed by systemic use of 5-FC leads to the inhibitory effect on tumor growth and metastatic activity in the o.t. mouse model of prostate cancer. Clinically, it may be possible to treat metastatic or recurrent prostate cancer with a novel gene therapy using in situ injection techniques in future.