Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation

CUI Tao; WU Weidang; CI Xiaoyan; LI Wei; GUO Chuanmin; XU Jing; YI Xiulin; LIU Changxiao

doi:10.11665/j.issn.1000-5048.20190207

Journal of China Pharmaceutical University > 2019 > 50(2): 175-179. > DOI: 10.11665/j.issn.1000-5048.20190207

CUI Tao, WU Weidang, CI Xiaoyan, LI Wei, GUO Chuanmin, XU Jing, YI Xiulin, LIU Changxiao. Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation[J]. Journal of China Pharmaceutical University, 2019, 50(2): 175-179. DOI: 10.11665/j.issn.1000-5048.20190207

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Evaluation of tolerance and pharmacodynamics of nano-micelle irinotecan formulation

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This study aimed to investigate the improvement of tolance and pharmacodynamics of nano-micelle irinotecan formulation compared with irinotecan hydrochloride injection(Campto). The toxic effects of the two formulations on colorectal cancer cells COLO205, HT-29, HCT-8 and SW480 were tested in vitro. COLO205 tumor-bearing mouse model was constructed. The two preparations were given via tail vein injection to investigate the maximum tolerance dose(MTD)of tumor-bearing mice to the two preparations, and then to explore the improvement of anti-tumor efficacy of nano-micelle irinotecan formulation near the MTD. The results showed that there was no significant difference in the inhibitory effect of the two formulations on the four colorectal cancer cells in vitro. The MTD of nano-micelle irinotecan formulation and Campto was 432. 0 and 276. 5 mg/m² respectively. Both of the two formulations showed significant anti-tumor effect in vivo, and the relative tumor proliferation rate and tumor wet weight inhibition rate of nano-micelle irinotecan formulation at high dose(345. 6 mg/m²)were significantly better than those of Campto at two doses(177. 0 and 221. 2 mg/m²)(P< 0. 05).
- irinotecan,
- nano-micelle,
- tolerance,
- pharmacodynamics,
- colorectal cancer

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[1]	Di B,Feng F,Yu LJ,et al.Studies on related substances of irinotecan,a new anticancer drug [J].J China Pharm Univ(中国药科大学学报),1999,30(3):36-38.
[2]	Rino Y,Yukawa N,Sato T,et al.Phase Ⅱ study on the combination of irinotecan plus cisplatin as a second-line therapy in patients with advanced or recurrent gastric cancer[J].Mol Clin Oncol,2013,1(4):749-752.
[3]	Petrelli F,Inno A,Ghidini A,et al.Second line with oxaliplatin- or irinotecan-based chemotherapy for gemcitabine-pretreated pancreatic cancer:a systematic review [J].Eur J Cancer,2017,81:174-182.
[4]	Zhang H,Zhang Y,Wang C,et al.Clinical research on therapeutic effect of combined application of lobaplatin and irinotecan in treating recurrant small cell lung cancer[J].Pak J Pharm Sci,2018,31(5):2295-2298.
[5]	Crozier JA,Advani PP,LaPlant B,et al.N0436(Alliance):a phase II trial of irinotecan with cetuximab in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane-containing therapy[J].Clin Breast Cancer,2016,16(1):23-30.
[6]	Shoji T,Takatori E,Omi H,et al.A phase II study of irinotecan and pegylated liposomal doxorubicin in platinum-resistant recurrent ovarian cancer(Tohoku Gynecologic Cancer Unit 104 study)[J].Cancer Chemother Pharmacol,2017,80(2):355-361.
[7]	Abou-Taleb HA,Koshiyama M,Matsumura N,et al.Clinical efficacy of neoadjuvant chemotherapy with irinotecan(CPT-11)and nedaplatin followed by radical hysterectomy for locally advanced cervical cancer[J].J Int Med Res,2016,44(2):346-356.
[8]	Femke M,de Man,Andrew KL,et al.Individualization of irinotecan treatment:a review of pharmacokinetics,pharmacodynamics,and pharmacogenetics[J].Clin Pharmacokinet,2018,57(10):1229-1254.
[9]	Maeda H, Fang J, Inutsuka T, et al. Vascular permeability enhancement in solid tumor:various factors,mechanisms involved and its implications[J].Inter Immunopharmacol,2003,3(3):319-328.
[10]	Matsumura Y,Maeda H.A new concept for macromolecular therapeutics in cancer chemotherapy:mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs[J].Cancer Res,1986,46:6387-6392.
[11]	Greish K,Fang J,Inutsuka T,et al.Macromolecular therapeutics,Advantages and prospects with special emphasis on solid tumortargeting[J].Clin Pharmacokinet,2003,42(13):1089-1105.
[12]	China Food and Drug Administration.Technical guidelines for non-clinical research on cytotoxic antitumor drugs [J].Chin J New Drugs Clin Rem,2008,27(6):462-465.

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