Advances in brain targeting

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RECENT ADVANCES IN BRAIN TARGETING

• Presented by
• Ms Surabhi R. Singh
• B.Pharm
• Guide
• Dr Suresh G. Sudke
• M.Pharm , PhD
• Department of Pharmaceutics

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Contents

• Introduction
• Diseases related to CNS
• Drugs acting on CNS
• Blood brain barrier (BBB)
• Transport of molecules across BBB
• Approaches to CNS drug delivery
• Major needs in Brain Targeting
• Marketed formulations
• Conclusions

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Introduction

• Drug delivery to brain is process of passing drug
  across the Blood Brain Barrier (BBB) for treating
  brain diseases.
• It is a complex process since brain has complex
  anatomy and restrictions imposed by the special
  junctions of BBB.
• Conventional drug delivery are insufficient to
  deliver drugs through BBB.
• Aggressive research efforts have recently focused
  on the development of new strategies to more
  effectively deliver the drugs to CNS.

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Diseases related to CNS

• Meningitis
• Brain abscess
• Epilepsy
• Multiple sclerosis
• Neuromyelitis optica
• Late-stage neurological trypanosomiasis
  (Sleeping sickness)
• Progressive multifocal leukoencephalopathy (PML)
• Alzheimer's Disease, etc

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Drugs Used to Treat CNS Disorders
LSD Imipramine Buspirone Lorazepam Tramadol Methad
one Naloxone Strychinine
Morphine Codeine Levodopa Diazepam Carbamazepine P
romethazine Haloperidol Alprazolam
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Blood Brain Barrier
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Transport of molecules across BBB
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Approaches to CNS Drug Delivery

• To overcome multitude of barriers restricting CNS
  drug delivery of potential therapeutic agents,
  numerous drug delivery strategies have been
  developed.
• These strategies generally fall into one or more
  of the following categories invasive,
  non-invasive or miscellaneous techniques

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Intra-cerebro-ventricular infusion

• Used extensively in clinical trials
• Infusion is done using a plastic reservoir
  (Ommaya reservoir) implanted SC in the scalp and
  connected to the ventricles within the brain via
  an outlet catheter.
• Only suitable for sites close to the ventricles.
• Eg Glycopeptide and aminoglycoside antibiotics

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Nanoparticles

• These are submicron drug carrier systems that are
  made from a broad number of materials such as
• Polysorbates
• Polyacetates
• Polysaccharides
• Polysorbate coated nanoparticles can mimic low
  density lipoproteins LDL to cross BBB

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Intra nasal drug delivery

• Absorption occurs by Transcellular and
  Paracellular passive absorption, carrier-mediated
  transport, and absorption through transcytosis.
• Olfactory mucosa may be reached and drug
  transport into the brain and/or CSF via the
  olfactory receptor neurons

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Iontrophoretic Intra Nasal Drug Delivery

• Direct nose-to-brain drug delivery circumvents
  BBB
• Multiple advantages over conventional
  intravenous delivery.
• However, demonstration of its clinical
  feasibility is still in trial.

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Major Needs In Brain Targeting

• Target therapeutics to specific brain regions or
  cell types
• Improve understanding of BBB transport systems
• Evaluation of brain drug pharmacokinetics
• Identify new brain drug targeting systems
• Speed development and application of molecular
  targeted contrast agents

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Recent Technology Combining Drugs And Pumps
1 Medstream progammable infusion pump and
control unit 2. Prometra pump and programmer 3.
Sychro Med infusion pump N vision clinical
programmer 4. Flownix prometra 5. Codman
medstream
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Marketed Formulations Available for Brain
targeting
Sr. No. Brand name Active Pharmaceutical ingredient Role
1 Ambisome Amphotericin B Liposome for injection
2 Aricept Donepezil Alzheimers disease
3 Aurimmune Colloidal gold 4 nanoparticles Solid tumor
4 Auroshell Gold coated silica nanoparticles Solid tumor
5 Caelyx PEGylated liposomal doxorubicin hydrochloride Brain tumor
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Conclusions

• Treatment of brain diseases is particularly
  challenging because delivery of drug molecules to
  brain is often blocked by BBB
• Drug delivery directly to brain has recently been
  markedly enhanced through rational design of drug
  delivery systems.
• Progress will only come, if continued vigorous
  research efforts are carried out.

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