Drug Delivery Nanosystems for the Localized Treatment of Glioblastoma Multiforme

Abstract

Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the intracranial space and the presence of the blood–brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood–brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.

Synthesis, Characterization, and In Vitro Studies of an Reactive Oxygen Species (ROS)-Responsive Methoxy Polyethylene Glycol-Thioketal-Melphalan Prodrug for Glioblastoma Treatment

“…Since the local administration of drugs has been investigated as it offers the possibility to bypass the BBB and blood brain tumor barrier (BBTB), concentrating higher amounts of drug in malignant tumors (Nam et al, 2018), it would be interesting to provide a locally sensitive strategy which would make it possible to have synergism with other actions including radiotherapy for the cleavage and drug activity. For the moment, pilot clinical studies using intravenous MPH have not shown any significant impact (Anderson et al, 2015).…”

Versatile magnetic microdiscs for the radio enhancement and mechanical disruption of glioblastoma cancer cells

“…The cytotoxicity of the magnetic microdiscs was assessed by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Abcam ab211091, Cambridge, UK). T98G cells were plated into 96 well plates (8000 cells per well) for 24 h. Then different concentrations of microdiscs (10,20,30,40 and 50 ND per cell) were added, the cells were cultured for another day.…”

<p>Verteporfin-Loaded Anisotropic Poly(Beta-Amino Ester)-Based Micelles Demonstrate Brain Cancer-Selective Cytotoxicity and Enhanced Pharmacokinetics</p>

“…To further improve tumor accumulation, an active targeting moiety, such as hyaluronic acid or folic acid, could be incorporated into the micelle design to target receptors overexpressed on GBM cells (ie CD44 and folate, respectively). 48,49 These ligands can be conjugated to the micelle surface in efforts to improve the chemotherapeutic impact and translational potential of these micelles.…”