Current Strategies for Brain Drug Delivery

Abstract

The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

Targeted brain tumor radiotherapy using an Auger emitter

“…A novel approach for treating GBM is therefore urgently needed, one that would address both pharmacodynamic as well as pharmacokinetic hurdles (3,4). Promising delivery strategies to overcome these problems in the clinics include convection enhanced delivery (CED) (5,6) and intrathecal injection (7,8).…”

Peptide based drug delivery systems to the brain

“…Different mechanisms can be adapted by the PMNPs to cross the BBB. They can cross the BBB either by transcytosis through endothelial cells, mucoadhesion, or by disturbing the TJ in the brain capillaries [102]. On the other hand, PMNPs can be identified upon i.v.…”

Focused ultrasound opening of the blood–brain barrier for treatment of Parkinson's disease

“…In some instances, improvements in drug delivery have been accomplished with new formulations, including controlled‐release preparations of oral pharmaceuticals, subcutaneous drug infusions, administration by pulmonary and intranasal routes, and prodrug versions of current therapies . At the cutting edge of improved technological options are lipid‐coated or magnetized nanoparticles, receptor‐mediated transcytosis, and vector‐assisted gene therapy, among others . For many of the developments intended to improve drug delivery to the CNS, the goal has been to circumvent limitations imposed by the blood–brain barrier (BBB) .…”

“…1,2 At the cutting edge of improved technological options are lipid-coated or magnetized nanoparticles, receptor-mediated transcytosis, and vector-assisted gene therapy, among others. 3 For many of the developments intended to improve drug delivery to the CNS, the goal has been to circumvent limitations imposed by the blood-brain barrier (BBB). 4 The vascular infrastructure comprising the BBB involves a specialized system of tight endothelial junctures and other perivascular components capable of blocking passive transluminal passage of most circulating molecules (especially those larger than 400-500 Da).…”