All-trans retinoic acid eluting poly(diol citrate) wafers for treatment of glioblastoma

Current treatments for glioblastoma have failed to significantly increase patient survival, are extremely cytotoxic, can cause severe side effects, and are ineffective. Given these limitations, drugs other than cytotoxic chemotherapeutic agents are being explored. Recent studies show that all-trans retinoic acid (ATRA) could be effective on cancer cells as they have been shown to suppress carcinogenesis in a variety of tumor types and can reverse premalignant lesions and inhibit the development of secondary tumors in the head and neck of cancer patients. However, the therapeutic effects of retinoids such as ATRA are undermined by its rapid in vivo metabolism by cytochrome P450 enzymes, difficulty in crossing the blood-brain barrier, and sensitivity to isomerization/degradation. To overcome these limitations, we have developed a porous poly(1,8-octanediol-co-citrate; POC) wafer that stabilizes all-trans retinoic acid, while slowly releasing ATRA over 3 months. Release of ATRA from POC wafers inhibited proliferation of U87MG (glioblastoma) cells and caused upregulation in genes associated with differentiation into normal phenotype and apoptosis. Therefore, ATRA eluting poly(diol citrate) wafers are a promising treatment option compared to traditional cytotoxic chemotherapeutic agents.