Paclitaxel Loaded Biodegradable Polymer Nanoparticles for Treatment of Glioblastoma

Glioblastoma multiforme (GBM) is a malignant primary brain tumor with a median survival time of 12-16 months despite aggressive treatment. Current care treatment consists of surgical resection, radiotherapy, and chemotherapy with temozolomide (TMZ). These therapies ultimately fail for most patients because of the resistant infiltrative nature of GBM, wide intratumoral heterogeneity, and complex suppressive microenvironment. Paclitaxel (PTX) is a promising chemotherapeutic agent with many important characteristics that could provide a powerful combination therapy with TMZ for treating GBM. PTX works by disrupting microtubule dynamics and the mitotic apparatus during cell division. PTX combined with an alkylating agent like TMZ synergistically has demonstrated significant effect in the treatment of other cancers. However, PTX cannot cross the blood brain barriers (BBB) system and therefore, its efficacy is limited in treating GBM patients. Multifunctional lipid polymer hybrid nanoparticles (LPNPs or NPs) represent an emerging class of drug delivery vehicles that can promote localized site-directed therapy to GBM via the intranasal (I.N.) route of delivery. Intranasal delivery of NPs encapsulated with PTX will offer a novel route of local delivery to the GBM without encountering the blood brain barriers and possess a novel strategy to target GBM tumor cells in the brain.