Chemotherapy Delivery Issues in Central Nervous System Malignancy: A Reality Check

Abstract

In this article, we review drug delivery across the BBB, as well as blood-tumor and -cerebrospinal fluid (CSF) barriers, and mechanisms to increase drug delivery to CNS and CSF tumors. Because of the difficulty in treating CNS tumors, innovative treatments and alternative delivery techniques involving brain/cord capillaries, choroid plexus, and CSF are needed.

Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain

“…FUS can temporarily disrupt the BBB, increasing local EPR in the CNS. This technology is ideally suited for transcranial delivery of drugs with molecular weights greater than 400 Da (1,14). However, although this technique works with substances with molecular weights as high as 150 kDa, penetration is still hampered at molecular weights of 2,000 kDa [approximately equivalent to 55 nm, as measured by TEM (15)].…”

Dual kinin B1 and B2 receptor activation provides enhanced blood–brain barrier permeability and anticancer drug delivery into brain tumors

“…These findings are significant given that the best method for delivering higher concentrations of intracerebral anticancer drugs remains elusive. 2,15 In addition, aside from being highly potent modulators of BBB/BTB, single molecules exhibiting mixed B1R/B2R agonist activity, such as the heterodimer described here, may provide a number of advantages over combination therapy with individual agonists. These include a single pharmacokinetic profile, a uniform ratio of activities at the cellular level and simpler in vivo preclinical testing in animal models.…”

“…1 The complexity of treating malignant gliomas is compounded by their highly infiltrative phenotype and the existence of the BBB, a powerful physiological barrier that seriously impairs the delivery of numerous anticancer drugs to tumor sites. 2 An intact or only partially compromised BBB may also explain the particular refractoriness and poor responses to chemotherapy of brain metastases, mainly arising from lung, breast and skin cancers. 3,4 Two basic types of experimental strategies have traditionaly been investigated to improve the effectiveness of anticancer drugs.…”

Glioblastoma multiforme y estudio de la resistencia a la quimioterapia mediada por transportadores ABC

“…Por lo tanto, la mejor alternativa para el manejo de este tipo de cáncer es optimizar la quimioterapia. Esto implica mejorar la biodisponibilidad de los fármacos antitumorales en las células que conforman el glioma, así como también aumentar su acceso al cerebro, en donde la barrera hematoencefálica (bHE) podría restringir el paso de los agentes antitumorales [8][9][10] .…”