Drug delivery to brain tumors

Abstract

A prerequisite for the efficacy of any cancer drug is that it reaches the tumor in therapeutic concentrations. This is difficult to accomplish in most systemic solid tumors because of factors such as variable hypoxia, intratumoral pressure gradients, and abnormal vasculature within the tumors. In brain cancer, the situation is complicated by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier, which serve as physical and physiologic obstacles for delivery of drugs to the central nervous system. Many approaches to overcome, circumvent, disrupt, or manipulate the BBB to enhance delivery of drugs to brain tumors have been devised and are in active investigation. These approaches include high-dose intravenous chemotherapy, intra-arterial drug delivery, local drug delivery via implanted polymers or catheters, BBB disruption, and biochemical modulation of drugs.

miR-182 integrates apoptosis, growth, and differentiation programs in glioblastoma

“…In particular, the BBB/BTB represents a major physiological barrier that often prevents the accumulation of therapeutic drug concentrations within intracerebral lesions. Delivery of RNA-based therapeutics is particularly challenging, since RNA can be unstable, often entrapped in endosomes, and incapable of infiltrating tumor parenchyma beyond perivascular regions (Blakeley 2008;Allhenn et al 2012). In a recent study, we characterized SNAs as a novel RNAi-based nanoconjugate using siRNAs designed to target Bcl2L12 (Jensen et al 2013).…”

New Non-Intravenous Routes for Benzodiazepines in Epilepsy: A Clinician Perspective

“…They are made of a polymer matrix with interwoven drug, releasing the medication over a prolonged period of time from weeks to years. Although this approach may have a rational for chemotherapy in brain tumors [54], it is definitely not indicated for the delivery of BDZ in the acute management of seizures.…”

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies

“…A variety of technologies have been modeled in a similar manner to wafer implants, ranging from tablets, liquids and injectable gels, to sophisticated systems utilizing bioengineered products to deliver different categories of drugs for brain tumor treatment ( Table 1). Many of these products use polymer-based drug delivery systems with each technology offering unique advantages to drug delivery and, insofar as they enhance BBB penetration and help to specifically target brain tumor cells [8,9], most should merit inclusion in the armamentarium for the treatment of malignant brain tumors. However, local drug delivery has attracted concerns due to the risks to healthy brain tissue, the need of a surgical procedure for implantation, and the limitations associated with either a single administration of therapy or controlled drug release over time [10][11][12][13].…”

“…Thus, the co-administration of chemotherapeutic agents with specific inhibitors of efflux transporters has attracted much attention for disrupting the BBB in a noninvasive, specific, and rapid manner [144,145]. In preclinical models, P-gp inhibitors have been shown to improve CNS penetration of paclitaxel, docetaxel and imatinib [8,146]. The use of first-generation P-gp inhibitors, such as verapamil and cyclosporine A, resulted in low binding affinities, unacceptable toxicity, and the inhibition of drug-metabolizing cytochrome P450 3A (CYP3A) enzymes.…”