Nanotechnology has applications in pharmaceutics including new drug delivery formulations and routes of administration. Nanoparticles can be engineered for controlled release of drugs and targeted delivery. Dendrimers are a type of synthetic nanoparticle that consists of branched monomers arranged around a core. They have potential applications for drug delivery due to their uniform size, water solubility and modifiable surface that allows drugs or targeting agents to be attached.

1. Nanotechnology in Pharmaceutics

2. Nanotechnology is an enabling technology Computing and Data Storage • Materials and Manufacturing • Health and Medicine • Energy • Environment • Transportation • National Security • Space exploration

3. New formulations and routes for drug delivery, optimal drug usage More durable, rejection-resistant artificial tissues and organs, implantable electrodes Sensors for early detection and prevention Nanotube-based biosensor for cancer diagnostics

4. Dissolution kinetics may be the rate limiting step in the absorption process for many drugs Decreasing the particle size increases surface area and the dissolution kinetics. Liposomes are normally used as carrier for hydrophilic drugs. Typical difficulties: physical instability, low activity, drug leakage Alternative: water-soluble polymer based nanoparticles. These are more site-specific and exhibit better controlled-release characteristics.

5. To overcome toxicity issues, solid lipid nanospheres as carrier systems have been reported*. This is a lipid that is solidified and stabilized by a surfactant. Advantages: physical stability Disadvantage: low drug loading (25%)

6. - Not more that 15 nm in size, Mol. Wt very high - Very dense surface surrounding a relatively hollow core (vs. the linear structure in traditional polymers) Tree-like polymers, branching out from a central core and subdividing into hierarchical branching units Courtesy of: http://www.uea.ac.uk/cap/wmcc/anc.htm

7. Dendrimers consist of series of chemical shells built on a small core molecule Surface may consist of acids or amines  means to attach functional groups  control/modify properties Each shell is called a generation (G0, G1, G2….) Branch density increases with each generation Contains cavities and channels  can be used to trap guest molecules for various applications.

8. Desired features of effective drug delivery Targeted delivery, controlled release (either timed or in response to an external signal) Desirable characteristics of dendrimers - Uniform size - Water Solubility - Modifiable surface functionality -Availability of internal cavity - Control of molecular weight - Control of the surface and internal structure

9. Number of different drugs can be encapsulated in dendrimers and injected into the body for delivery - Incorporating sensors would allow release of drugs where needed Gene Therapy - Current problem is getting enough genes into enough cells to make a difference. - Using viruses for this triggers immune reactions. Dendrimers provide an alternative without triggering immune response Cancer Therapy Antimicrobial and Antiviral Agents

10. Potential applications: Lab-on-a-chip applications Early cancer detection Infectious disease detection 30 dies on a 4” Si wafer 200  m 300  m

11. Nanopore in membrane (~2nm diameter) DNA in buffer Voltage clamp Measure current

12. Medtronic WHY: Effective Clinical Technique DBS has been clinically effective in the treatment of movement disorder HOW: Four Interrelated Hypothesis Paradox of similar effects to lesioning of target structure is explained by the following: Depolarization Blockage Synaptic Inhibition Synaptic Depression Stimulation Induced Modulation of Pathways PROBLEMS: Indiscriminate Activation Stimulation indiscriminately affects all tissue around the electrode (size: 1.27mm diameter with four 1.5mm contacts) Crude method without feedback IMPROVEMENTS: Targeted Activation to specific location down to sub mm scale Obtain feedback information – such as neurotransmitter levels