Route
Explanation
Example
Bypass the BBB
- Direct administration into the CSF bypasses the BBB to reach structures within the CNS
- Intrathecal antibiotics to treat meningitis or ventriculitis
- Intrathecal chemotherapy agents to treat CNS malignancy
Increase the lipophilicity of drug
- Increased lipophilicity of aids passive diffusion across lipid membranes of the BBB
- Heroin has to acetyl groups added to morphine molecule making it 100x more lipid soluble - produces more rapid onset of action
- Once within the brain metabolised to morphine, which only slowly leaves the brain
Increase permeability of BBB
- Increased permeability my be due to disease or induced by vasoactive compounds (such as bradykinin and histamine) to enhance drug delivery
- Delivery of chemotherapeutic agents into the brain
- Delivery of certain antibiotics enhanced by inflammation in meningitis
'Prodrug' to Utilise BBB Transport Mechanisms
- Prodrugs which cross the BBB may be used which are subsequently metabolised in the brain to active compounds
- The neurotransmitter dopamine cannot cross the BBB
- The precursor L-DOPA is transported across the BBB by facilitated diffusion where it is subsequently converted to dopamine
- It is used in Patients with Parkinson’s disease, in which there is a dopamine deficiency of the substantia nigra
'Trojan Horse' Delivery to Utilise BBB Transport Mechanisms
- A monoclonal Ab (Mab) acts as a molecular Trojan horse to deliver drugs across the BBB
- A drug pharmaceutical is genetically fused to the MAb
- The MAb acts against receptors on cells of the BB such as the insulin receptor leading to transport across the cell via transcytosis
- Early clinical trials for specialist treatments