Blood brain barrier: An overview on strategies in drug delivery, realisticin vitromodeling andin vivolive tracking

Abstract

Blood brain barrier (BBB) is a group of astrocytes, neurons and endothelial cells, which makes restricted passage of various biological or chemical entities to the brain tissue. It gives protection to brain at one hand, but at the other hand it has very selective permeability for bio-actives and other foreign materials and is one of the major challenges for the drug delivery. Nanocarriers are promising to cross BBB utilizing alternative route of administration such as intranasal and intra-carotid drug delivery which bypasses BBB. In future more optimized drug delivery system can be achieved by compiling the best routes with the best carriers. Single photon emission tomography (SPECT) and different brain-on-a-chip in vitro models are being very reliable to study live in vivo tracking of BBB and its pathophysiology, respectively. In the current review we have tried to exploit mechanistically all these to understand and manage the various BBB disruptions in diseased condition along with crossing the hurdles occurring in drug or gene delivery across BBB.

Current progress on microRNAs‐based therapeutics in neurodegenerative diseases

“…To overcome this issue, two modalities have been applied for drug transport across the BBB, namely invasive and noninvasive approaches (Table ). The invasive approaches are directed to CNS delivery, including intracerebroventricular infusion, intrathecal, convection‐enhanced delivery, and the disruption methods of BBB integrity . These approaches have a high risk of side effects (such as infection, edema, and neuron damage), as well as some drawbacks, namely the safety profile, inconvenience, and high cost.…”

“…On the other hand, noninvasive approaches are of better patient compliance and are more suitable for NDs therapy. These include lipid‐mediated drug transport, systemic intravenous administration, intranasal delivery, and strategies using nanosystems (see section below) …”

Blood–brain barrier and laser technology for drug brain delivery

“…There are more than 70 di®erent physical, chemical and biological methods for overcoming of the BBB. [51][52][53][54] However, no approaches for the opening of BBB, which are widely used in daily clinical practice due to their invasiveness and challenge in performing such as intra-arterial injection of mannitol, limitation of drug concentration using intranasal drug delivery or area of treatment (1-3 mm) using focused ultrasound. [55][56][57] Here, we discuss technology, which is used in clinical practice but with completely new view on this method as novel approach for the brain drug delivery.…”

Loud music and the specific sound stress open the blood-brain barrier: new fundamental, biomedical, and social aspects

“…Now we are in the era for the development of approaches for brain drug delivery. Indeed, currently over 70 different methods were suggested for overcoming BBB including physical, chemical and biological approaches [4][5][6] . Nevertheless, these methods are not widely applied in daily clinical practice due to many reasons including invasiveness (e.g., photodynamic opening of BBB that requires skull opening) 7 , challenge in performing (intraarterial injection of mannitol that only few specialists in clinics can usually do) 8 , limitation of drug concentration (intranasal drug delivery) 9 or small area of treatment (only 1-3 mm at usage of focused ultrasound that opens BBB with additional using of micro-bubbles) 10 .…”