Blood–brain barrier and laser technology for drug brain delivery

Oxana V Semyachkina-Glushkovskaya,Nikita V Navolokin,Elena I Saranceva,Arkady S Abdurashitov,Alexander A Shirokov,Eketerina G Borisova

doi:10.1142/s1793545817300117

Abstract

Here, we discuss an important problem in medicine as development of effective strategies for brain drug delivery. This problem is related to the blood–brain barrier (BBB), which is a “customs” controlling the entrance of different molecules from blood into the brain protecting the normal function of central nervous system (CNS). We show three interfaces of anatomical side of BBB and two functional types of BBB — physical and transporter barriers. Although this protective mechanism is essential for health of CNS, it also creates a hindrance to the entry of drugs into the brain. The BBB was discovered over 100 years ago but till now, there is no effective methods for brain drug delivery. There are more than 70 approaches for overcoming BBB including physical, chemical and biological techniques but all of these tools have limitation to be widely used in clinical practice due to invasiveness, challenge in performing, very costly or limitation of drug concentration.Photodynamic therapy (PDT) is usual clinical method of surgical navigation for the resection of brain tumor and anti-cancer therapy. Nowadays, the application of PDT is considered as a potential promising tool for brain drug delivery via opening of BBB. Here, we show the first successful experimental results in this field discussing the adventures and disadvantages of PDT-related BBB disruption as well as alternatives to overcome these limitations and possible mechanisms with new pathways for brain clearance via glymphatic and lymphatic systems.

Highlights

We discuss an important problem in medicine as development of e®ective strategies for brain drug delivery
This problem is related to the blood–brain barrier (BBB), which is a \customs" controlling the entrance of di®erent molecules from blood into the brain protecting the normal function of central nervous system (CNS)
Despite the fact that Enrlich did not understand the paradoxical futures of BBB and Gordman made historical error owing to belief that anatomical side of the BBB is of choroid plexus, the concept of BBB is attributed to these two names.[4]

Summary

The First 100 Years of BBB Research and Nowadays

The history of blood–brain barrier (BBB) begins from the end of 19th century. In 1885, Paul Ehrlich studied anti-bacterial e®ects of di®erent acidic vital dyes and observed that if dyes were injected intravenously, they would stain peripheral organs except brain and spinal code (the choroid plexus was stained, but cerebrospinal °uid (CSF) was not).[1]. In 1928, Stern and Rapoport clearly showed existing two routes of entry from blood into brain: one directly across the microvessels — the endothelial BBB and the other via the choroid plexus — the epithelial blood–CSF barrier.[9,10] The arachnoid barrier is mentioned as special type of barrier. It is avascular epithelial barrier, which separates the sagittal sinus from the dura projecting arachnoid villi into this main cerebral vein, thereby allowing the CSF movement out of the brain to blood. Until the late 1950s, many researchers had doubts that the physical barriers exist and the progress in the study of BBB actively started after the 1960s due to progress in optical visualization of brain tissues and vessels.[11]

The Structure and Functions of Barriers Between Blood and Brain

Transport Systems Across BBB

Photodynamic Therapy as a Potential Tool for Brain Drug Delivery

Conclusion