Polymeric micelle (PM) drug carriers were invented a quarter of century ago. 1 Today nearly a dozen of drug formats based on PM undergo clinical trials and one product, Genexol-PM, a PM paclitaxel, was approved for cancer therapy in South Korea. 2 The value proposition of PM drugs includes increased drug solubility, passive distribution and targeting to disease sites. Poly(2- oxazoline) PM display unprecedented high loading with respect to insoluble drugs. 3 This PM platform has been validated for more than 20 very poorly soluble active pharmaceutical<br/>ingredients (APIs) of different classes. It has demonstrated potential to increase treatment efficacy of cancers by using high-dose therapy and shown superiority in treatment of tumors in animal models. 4 Systemic therapies for brain tumors are complicated by dose-limiting extraneural toxicity, serum protein binding and restricted blood-brain barrier (BBB) permeability. For patients with SHH-subgroup medulloblastoma, SHH-pathway inhibition may be more effective and less toxic than current non-targeted therapy. However, vismodegib, which effectively targets SHH-driven basal cell carcinoma, has limited benefit for patients with SHH-driven medulloblastoma. Formulating vismodegib in poly(2-oxazoline) micelles (POx-vismo) improved delivery and efficacy, using medulloblastoma-prone hGFAP-Cre/SmoM2 (G-Smo) mice for a preclinical model. Compared to conventional vismodegib (c-vismo), POx-vismo increased maximum tolerated dose (MTD), tumor:serum ratio and penetration to brain and tumor. Our results show the potential for POx-vismo to improve medulloblastoma treatment,<br/>demonstrating the potential for poly(2-oxazoline) micelles delivery to make failed brain tumor treatments newly effective.

Hyperloaded poly(2-oxazoline) micelles as personalized drug carriers for brain tumors

2019 Fall National Meeting

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