Treating brain tumors with targeted-micelles containing immunotherapeutics

A-M. Broome, S. Dixit, K. Miller, A. Moore, A-L. Bredlau
Medical University of South Carolina, US

Keywords: glioma, micelle, rapamycin, immunotherapeutic delivery

Summary:

The development of selectively targeted nanoparticles that can act as drug delivery vehicles is critical for improving the treatment and monitoring of glioblastoma, a life threatening disease. Rapamycin (Sirolimus, rapa), a large, lipophilic carboxylic lactone-lactam macrolide antibiotic, is recognized for its potent anti-proliferative and immunosuppressive effects in vitro and in vivo. These properties make rapa a potential chemotherapeutic agent against several tumors. Despite its promising properties, clinical applications of rapa have been limited due to its hydrophobicity, limiting its utility as an intravenously administered drug. Presently, the commercially available formulations of rapa include tablet or oral forms. Nevertheless, the low oral bioavailability of rapa limits the effectiveness of both of these forms. In addition, the lipophilicity makes the drug susceptible to attachment to the lipid membranes of normal as well as cancer cells. A selectively targeted carrier for rapa will enhance its delivery to malignant cells, avoid non-specific interactions, and reduce non-tumor toxicity.