Drug delivery system for active brain targeting - Artificial Cells, Cell Engineering and Therapy - page 405

17.1 Schematic comparison between general and brain capillaries; see text for
details.
(BCSFB), which is located at the choroid plexuses. Since the surface area of the
human BBB is estimated to be 5000 times greater than that of the BCSFB, the
BBB is considered to be the main region controlling the uptake of drugs into the
brain parenchyma and the target for delivering drugs to the brain. Furthermore,
the relatively high blood flow of the brain is also an obstacle.
For the above reasons, the brain is probably one of the least accessible
organs. Small electrically neutral, lipid-soluble molecules can readily penetrate
the BBB; however, many chemotherapeutic agents that are large, ionically
charged or hydrophilic do not fall into this category, and thus are difficult to
transport into the CNS (Fig. 17.1). It is, therefore, the major obstacle to drugs
that combat diseases affecting the CNS because of these unique characteristics
of the brain.
17.2 Strategies for delivering drugs to the brain
To the BBB, drugs are foreign molecules that are not allowed to enter the
cerebrospinal fluid and gain access to brain cells. While the exclusion of foreign
molecules is highly desirable under normal circumstances, cerebral drug delivery
is faced with many obstacles owing to the unique anatomic and physiological
characteristics of the brain. These present serious problems for medical treatment
of cancer and other diseases of the brain. Thus, the development of efficient
drugs and drug carriers capable of entering the brain has become a major
challenge; various strategies have been devised to improve brain drug delivery
and accumulation as follows:
· Preparation of lipid soluble analogs or prodrugs.
· Direct injection into brain or CSF.
· BBB modification.