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Local delivery of slow-releasing temozolomide microspheres inhibits intracranial xenograft glioma growth

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Abstract

Background

Currently, treatment of malignant gliomas with temozolomide in addition to surgical resection and radiotherapy remains the foundation of glioma therapy. In an effort to develop new therapeutic choices to treat malignant gliomas, we have designed slow-releasing microspheres that deliver temozolomide (P-TMZ). The local continuous release of temozolomide at the intracranial tumor site may overcome many obstacles associated with systemic delivery, which will help to further improving the therapeutic effects against malignant gliomas.

Methods

Slow-releasing microspheres containing 10 % temozolomide were prepared, the antitumor efficacy in vitro was evaluated with MTT assay, and the therapeutic efficacy in vivo against gliomas was assessed in human glioma (SGH44) nude mice s.c. and orthotopic xenograft models.

Results

A single local injection of P-TMZ led to significant reduction both in s.c. and orthotopic human SHG44 glioma xenografts. P-TMZ, BCNU and TMZ had significant antiglioma effect (P < 0.01), their IC50 value was all less than 10 μg/ml. Tumor inhibition ratio of P-TMZ, BCNU and TMZ in vivo was higher than empty microspheres P0 (P < 0.01); P-TMZ and BCNU showed higher antitumor efficacy than TMZ (P < 0.05).

Conclusions

Our present results suggest that local delivery of slow-releasing temozolomide microspheres is effective for malignant gliomas. P-TMZ retained good antitumor activity and had better therapeutic effect against glioma both in vitro and in vivo, which provide a new choice for future clinical interstitial chemotherapy.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (No. 81071766) and Natural Science Foundation of Jiangsu Province, China (BK2010227). We thank Dr. Hailong Yang (Chemical Medicine Laboratory, Tianjin Tasly Institute, Tianjin, 300402, China) for kindly offering TMZ and slow-releasing temozolomide microspheres.

Conflict of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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Authors and Affiliations

  1. Department of Neurosurgery, 2nd Affiliated Hospital of Suzhou University, Suzhou, 215004, China

    Jun Dong, Guanghua Zhou, Dongfang Tang, Yanming Chen, Baoqian Cui, Xingliang Dai, Jinshi Zhang, Qing Lan & Qiang Huang

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  1. Jun Dong
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  2. Guanghua Zhou
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  3. Dongfang Tang
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  4. Yanming Chen
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  7. Jinshi Zhang
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  8. Qing Lan
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  9. Qiang Huang
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Correspondence to Jun Dong.

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Dong, J., Zhou, G., Tang, D. et al. Local delivery of slow-releasing temozolomide microspheres inhibits intracranial xenograft glioma growth. J Cancer Res Clin Oncol 138, 2079–2084 (2012). https://doi.org/10.1007/s00432-012-1290-3

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  • DOI: https://doi.org/10.1007/s00432-012-1290-3

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