Brain targeting

Unit I
M.pharmacy I
Neha Srivastava
 Introduction
Slide Title
• Blood brain barrier
• Diverse etiology of brain and
impermeability to drugs
• Small lipid molecules can penetrate
• Newer Strategies
 Introduction
Slide Title
Fluid brain barrier
• BBB
• Blood cerebrospinal fluid
• Nose brain barrier
• Arachnoids matter- CSF barrier
 Introduction
Slide Title
Fluid brain barrier
• Endothelial membrane
• Express various functional proteins
• Peptides are involved in BBB transfer
• No paracelluar pathway
• No pinocytosis
• Lipid mediated transport
• Catalyzed transport
 Introduction
Slide Title
Fluid brain barrier
Glucose, amino acids saturable blood brain
barrier system
 Function
Slide Title
Function of BBB
 Specific transport system
 Enzymes in endothelial cells
 Protection and nutrients supply
 Function
Slide Title
BBB as Active Pump
 Movement of K ions
 Na K ATPase pump
 Ion transport
• Polarity of cell
• Tight junction, electric resistance, low
conductance, high mitochondrial activity
• Active transport
• BBB secrete fluid
• Other Sodium Transporter
 Introduction
Slide Title
BBB as Active Pump
 Movement of K ions
 Na K ATPase pump
 Ion transport
• Polarity of cell
• Tight junction, electric resistance, low
conductance, high mitochondrial activity
• Active transport
• BBB secrete fluid
• Other Sodium Transporter
 Function
Slide Title
BBB as Metabolic barrier
 Cytoplasm and organelles
 Enzymes for neurotransmitter synthesis and
degradation
 L-Dopa by L-system
 Intraendothelial metabolism
 Neurotransmitter degrading enzymes on
aluminal side
 Acid hydrolase, angiotensin converting
enzymes, xantine oxidase
 MAO
 Regulation
Slide Title
Regulation of BBB function
 Neurotransmitter or hormone binding site
 Beta adrenergic blockers
 Atrial natriuretic peptides receptors
 Receptors for insulin, vasopressin,
transferrin
 Limitation
Slide Title
Limitation of Brain Uptake
 Inability to reach and maintain active
concentration

Factor affecting Brain targeting

 Time dependent plasma concentration
 Binding of agent to plasma constituents
 Permeability of the BBB
 Local cerebral blood flow
 Brain
Slide drug delivery system
Title
Neurosurgical or Invasive strategies
Hyperosmoler BBB Disruption
 Hypertonic solution
 Shrinking of cells and stretching of
junctions
 More effective in normal brain than tumor
brain
 Brain
Slide drug delivery system
Title
Intraventricular drug infusion
 Effective method
 Poorly delivers to brain parenchyma
 Brain
Slide drug delivery system
Title
Intracerebral Implants
 Bioartificial prosthesis
 Neurosecretory cells surrounded by semi
permeable membrane
 Biological sustained release system

 Brain
Slide drug delivery system
Title
Physiologic based strategies
Pseudonutrients
 Mimic nutrients
 Hexose, basic acids, nucleosides, amino
acids

Cationic Antibodies
 Positively charged molecules undergoes
absorption mediated transcytosis
 No tissue toxicity, non immunogenic in
nature
 Brain
Slide drug delivery system
Title
Chemeric Peptides
 Peptide specific receptor system
eg: insulin, transferring
 Absorptive mediated transport system
eg: cationic albumin, lecithin
 Receptor mediated endocytosis
 Scavenger receptor – endocytosis of low
density lipoproteins
 Anchoring drug
 Brain
Slide drug delivery system
Title
Chemeric Peptides
 Two principles
1: Vector itself have biological activity
2: Uptake markly reduced
Polycationic proteins
Cationic molecules
B- endorphin chimeric peptides
 Brain
Slide drug delivery system
Title
Chemeric Peptides
Steps
1) Absorptive mediated endocytosis
2) Completion toward brain side
3) Distribution in interstitial
4) Cationic group of vector and anionic group
of surface
 Brain
Slide drug delivery system
Title
Chemeric Peptides
Steps

1) Cleavage of disulfide bond of drug and

vectors
2) Disulfide reductase enzymatic activity
3) Receptor binding
 Brain
Slide drug delivery system
Title
Pharmacological strategies
Drug trapped in somes
Chemical delivery system
1) Chemical modification to increase lipid
solubility
2) Linking with methyldihydropyridine
3) Redox delivery system
 Brain
Slide drug delivery system
Title
Small Colloidal Particles
Nanoparticles
1) Coating with poloxomer
2) Polysorbate 80 increase uptake

Liposomes

Monocytes