1. Conjugation of BACLOFEN to magnetic nanoparticles InduVenugopal Advisor: Prof. Andreas Linninger Laboratory of Product and Process Design February 8th, 2012

2. Spasticity • Muscle control disorder in which the muscles feel an unusual tightness along with the inability to control them. • Found in people with cerebral palsy, traumatic brain/spinal cord injury, stroke and multiple sclerosis Cause Damage to the CNS loss of control of motor neurons excitability of muscle spindles synaptic inhibition Imbalance of signals from CNS to the muscles

3. Current treatment: Baclofen(Lioresal) • Derivative of gamma-aminobutyric acid (GABA) • Acts as an agonist for GABAB receptors. • Has an inhibitory effects on spinal cord reflexes and brain. • Administration routes: • Oral: Not very effective • Intrathecal: More effective but very expensive and uncomfortable. Structure of Baclofen

4. Method of Action of GABA/Baclofen • GABA • Regulate the [Cl- ] • Prevents over excitability of neuronal cells GABABreceptors • 7 α-helical structures with a tight opening in the centre • Only permits Cl- ion to pass • Can create a membrane potential.

5. Conjugation to Fe3O4@Au nanoparticles (DMSA: Dimercapto-succinimid acid)

6. EDAC coupling reaction B Baclofen B B Baclofen bound via amide bond Baclofen Carboxyl-modified MNPs

7. Questions?