Therapeutic Effectiveness Of Slow-releass PLGA-Oxaliplatin Microsphere On Human Colorectal Tumor

Object To study the acute toxicity and antitumor effect on xenograft colorectal tumor of slow-release PLGA-Oxaliplatin microsphere.Method Acute toxicity study:slow-release Oxaliplatin microsphere and Oxaliplatin were injected subcutaneously to healthy rat. Bliss method was used to determine the LD50. Drug effect study:60 tumor-bearing nude mice were randomly separated into 6 groups as follows (10 mice/group):groupⅠ, no treatment; groupⅡ, treatment with 32mg of PLGA microsphere; groupⅢ, treatment with 4mg/kg of Oxaliplatin; groupⅣ, treatment with 8mg/kg of Oxaliplatin; groupⅤ, treatment with 20mg/kg of PLGA-Oxaliplatin microsphere (4mg/kg of Oxaliplatin); groupⅥ, treatment with 40mg/kg of PLGA-Oxaliplatin microsphere (8mg/kg of Oxaliplatin). Treatment started 7 days after inoculation when tumors developed in right flank.after the drug injection, health condition and the size of the tumor were observed. At the end of the experiment, the weight of the tumor was monitered, the tumor expression of PCNA and TUNEL was measured in all groups.Results The LD50 of PLGA-Oxaliplatin microsphere on mice was 660.90mg.kg-1, Oxaliplatin was 15.24mg.kg-1. PLGA-Oxaliplatin significantly restrained the tumor growth and the therapeutic effect was correlated with decreased expression of PCNA and increased expression of TUNEL in tumor cells. Body weight measurement and blood analysis showed little side effect happened during the study.Conclusion PLGA-Oxaliplatin microsphere can markedly reduce the acute toxicity of Oxaliplatin on mice. PLGA-Oxaliplatin microsphere developed here was safety and effective in control the tumor growth, the preparation is expected to reduce local recurrence of colorectal cancer after resection and worth of further investigation.