Overcoming the Blood–Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours

Whenever we do get drugs that help stroke recovery; axon pathfinding, neurite outgrowth, neurogenesis migration to injury site, then our researchers will have a readily available delivery mechanism. Assuming of course that they keep up-to-date on relevant research.  Which we would be able to if we had a database of all stroke research and protocols. But we don't because we have fucking failures of stroke associations instead.

Overcoming the Blood–Brain Barrier: Successes and Challenges in Developing Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours

Authors Ferraris C, Cavalli R, Panciani PP, Battaglia L
Received 23 February 2020
Accepted for publication 14 April 2020
Published 30 April 2020 Volume 2020:15 Pages 2999—3022
DOI https://doi.org/10.2147/IJN.S231479
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Thomas J Webster

Chiara Ferraris,¹ Roberta Cavalli,¹ Pier Paolo Panciani,² Luigi Battaglia<sup>1

1</sup>Department of Drug Science and Technology, University of Turin, Turin, Italy; ²Clinic of Neurosurgery, Spedali Civili and University of Brescia, Brescia, Italy

Correspondence: Luigi Battaglia Email luigi.battaglia@unito.it

Abstract: 

High-grade gliomas are still characterized by a poor prognosis, despite recent advances in surgical treatment. Chemotherapy is currently practiced after surgery, but its efficacy is limited by aspecific toxicity on healthy cells, tumour cell chemoresistance, poor selectivity, and especially by the blood–brain barrier (BBB). Thus, despite the large number of potential drug candidates, the choice of effective chemotherapeutics is still limited to few compounds. Malignant gliomas are characterized by high infiltration and neovascularization, and leaky BBB (the so-called blood–brain tumour barrier); surgical resection is often incomplete, leaving residual cells that are able to migrate and proliferate. Nanocarriers can favour delivery of chemotherapeutics to brain tumours owing to different strategies, including chemical stabilization of the drug in the bloodstream; passive targeting (because of the leaky vascularization at the tumour site); inhibition of drug efflux mechanisms in endothelial and cancer cells; and active targeting by exploiting carriers and receptors overexpressed at the blood–brain tumour barrier. Within this concern, a suitable nanomedicine based therapy for gliomas should not be limited to cytotoxic agents, but also target the most important pathogenetic mechanisms, including cell differentiation pathways and angiogenesis. Moreover, the combinatorial approach of cell therapy plus nanomedicine strategies can open new therapeutical opportunities. The major part of attempted preclinical approaches on animal models involves active targeting with protein ligands, but, despite encouraging results, a few number of nanomedicines reached clinical trials, and most of them include drug-loaded nanocarriers free of targeting ligands, also because of safety and scalability concerns.