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

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.