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[丝裂霉素C结合活性炭纳米粒对人胃癌裸鼠进行腹腔化疗]

[Intraperitoneal chemotherapy with mitomycin C bound to activated carbon nanoparticles for nude mice bearing human gastric carcinoma].

作者信息

Qu Qiu-lian, Zhang Ying-ge, Yang Liu-zhong, Sun Lan

机构信息

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2006 Apr;28(4):257-60.

Abstract

OBJECTIVE

To prepare a new dosage formulation of activated carbon nanoparticles adsorbing mitomycin C (MMC-ACNP) and evaluate the beneficial effects of intraperitoneally applied MMC-ACNP as a drug delivery system for lymphatic targeting in preventing metastasis and recurrence of gastric cancer.

METHODS

MMC-ACNP was prepared. Acute toxicity after its intraperitoneal administration was evaluated. An experiment on nude mice model with transplanted human gastric cancer in 6 groups was completed to assess the effects of drugs on intra-abdominal carcinomatosis.

RESULTS

The LD50 of MMC-ACNP was 46.80 mg/kg (in terms of MMC) while that of MMC aqueous solution was 9.33 mg/kg. The toxicity of MMC-ACNP was much less than that of the solution form. MMC-ACNP was superior to MMC aqueous solution in controlling carcinomatosis and tumor growth by intraperitoneal administration. Despite the high dose of MMC, leukopenia and thrombocytopenia were not observed in the MMC-ACNP treated group. Fine activated carbon particles adsorbing MMC entered the nuclei of tumor cells, so that the effects of the anticancer drug were reinforced.

CONCLUSION

MMC-ACNP gives a good promise of clinical use due to its advantages such as high selectivity and low toxicity.

摘要

目的

制备一种吸附丝裂霉素C的新型活性炭纳米颗粒剂型(MMC - ACNP),并评估腹腔注射MMC - ACNP作为一种淋巴靶向给药系统在预防胃癌转移和复发方面的有益效果。

方法

制备MMC - ACNP。评估其腹腔注射后的急性毒性。完成对6组人胃癌移植裸鼠模型的实验,以评估药物对腹腔内癌转移的影响。

结果

MMC - ACNP的半数致死量为46.80 mg/kg(以MMC计),而MMC水溶液的半数致死量为9.33 mg/kg。MMC - ACNP的毒性远低于溶液剂型。腹腔注射时,MMC - ACNP在控制癌转移和肿瘤生长方面优于MMC水溶液。尽管MMC剂量高,但MMC - ACNP治疗组未观察到白细胞减少和血小板减少。吸附MMC的细小活性炭颗粒进入肿瘤细胞核,从而增强了抗癌药物的效果。

结论

MMC - ACNP因其高选择性和低毒性等优点,具有良好的临床应用前景。

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