ABSTRACT
The brain is one of the critical organs of our body, which is difcult to access when it comes to the treatment of brain-related ailments. The two main barriers, which act as hindrance, are the blood-brain barrier (BBB) and the blood-cerebrospinal uid barrier (BCSFB) that prevent the entrance of endogenous substances and xenobiotics. The tightly bound BBB is composed of endothelial cells, astrocytes end feet,
5.1 Introduction .................................................................................................. 113 5.2 CNS Diseases ............................................................................................... 115 5.3 Physiological Barriers to CNS Drug Delivery .............................................. 115
5.3.1 Blood-Brain Barrier (BBB) .............................................................. 115 5.3.2 Blood-Cerebrospinal Fluid Barrier (BCSFB) .................................. 116 5.3.3 Blood-Tumor Barrier ........................................................................ 117
5.4 Mechanism of Solute Transport across BBB ................................................ 118 5.5 Physicochemical Factors Affecting Drug Permeation through BBB ........... 119 5.6 Novel Carriers and Newer Options for Brain Targeting ............................... 119
5.6.1 Intracerebro Ventricular Infusion ..................................................... 120 5.6.2 Use of Implant .................................................................................. 120 5.6.3 Drug Transport via Tight Junction Opening .................................... 120
5.6.3.1 BBB Disruption by Biological Stimuli .............................. 121 5.6.3.2 BBB Disruption by Chemical Stimuli ............................... 122 5.6.3.3 Development of Physical Stimuli ....................................... 122
5.6.4 Nanoscale Systems for Brain Drug Delivery.................................... 123 5.6.4.1 Polymeric Nanoparticles ....................................................124 5.6.4.2 Micelles .............................................................................. 126 5.6.4.3 Liposomes .......................................................................... 127 5.6.4.4 Functionalized Nanocarriers: PEGylation
of Nanocarriers .................................................................127 5.6.4.5 Use of Drug Transport via Cell-Penetrating Peptides ....... 128 5.6.4.6 Drug Transport via Endogenous Receptor-Mediated
Transcytosis ....................................................................... 128 5.7 Conclusion .................................................................................................... 129 References .............................................................................................................. 129
and pericytes, and tight junctions are present between the cerebral endothelial cells. This cerebral endothelial cell differs from the rest of the endothelial cells of the body due to the absence of fenestrations with very few pinocytic vesicles and increased numbers of mitochondria. There is also a lack of lymphatic drainage and absence of major histocompatibility complex (MHC) antigen in the central nervous system (CNS) with immune reactivity inducible on temporary demand in order to provide maximum protection to neuronal functions. It may be in trace amounts, but some enzymes also play a part in this BBB such as glutamyltranspeptidase, alkaline phosphatase, esterase, and monoamine oxidase.
