Nano-scale Drug Delivery Modern Structures and Materials

1. Nano-scale Drug DeliveryModern Structures and Materials ECE 510 30April2008 Ed Katz

2. Introduction Definitions: �Nano Scale�- a structure with at least one dimension less than 100 nm �Drug�- A substance introduced into the body to alter functionality This includes Proteins, plasmid DNA, and so forth Many current delivery systems fit this description Research is focused on manipulating structures at this scale to create drug-delivery functionality

3. Why work with nanoscale drug delivery systems? We would like to minimize side effects while maximizing efficacy- our main tool is to distribution Ideally we would like our delivery system to provide: Long circulation time Present at target in sufficient quantity No loss of efficacy

4. Long circulation time- Particle size Small particles (<10 nm) are lost to extravasation (absorption into tissue) Large Particles (>200 nm) are quickly captured and excreted Particles between 70 and 200 nm show longest circulation time Particles between 10 and 70 nm penetrate capillary vessels Active Targeting Bioactive substances can be triggered to release drugs at target area, protect drug in transit from Active Targeting Bioactive substances can be triggered to release drugs at target area, protect drug in transit from

5. Managing Distribution Barriers Blood-Brain Barrier Non-ionized, lipophilic materials Epithelial junctions in skin Gene transfection Targeting of sub cellular structures Loss of efficacy Some drugs must be protected while in circulation This is the motivation for a number of the structures below

6. Structures Nanocapsules Nanotubes Nanogels Dendrimers Nanoshells Other Structures

7. Structures-Nanocapsules Encapsulated structures protect drugs, allow for surface modification For our purposes, we will consider fully enclosed structures nanocapsules, partially enclosed and plugged structures will be dealt with under nanoshells and nanotubes We will deal mainly with liposomes

8. Lipisomes Closed, continuous bi-layered structure Synthesized with polymers Tendency to aggregate and fuse We would like to make them stable for storage and application (Liposome (1999) by Kosi Gramatikoff user:kosigrim)

9. Liposome Micelles in Practice

10. Structures- Nanotubes Larger internal volume Inner and outer surfaces can be separately functionalized Simple loading Can be grown on templates Control of size and shape Typically carbon or silica Can be �corked� with a bioactive or actively triggered particle Successful applied in �spears� for gene transfection Some anti-oxidant, anti-microbial properties Some possible toxicity

11. Nanotubes in practice

12. Structures- Nanogels Can be synthesized and stored without drugs, subsequently loaded Extended stability Low Toxicity Limited methods for surface coating

13. Structures- Nanogels

14. Structures- Dendrimers Controlled shape Relatively easy to isolate Drugs can be �enveloped� by structure or bonded to branches Increasing size increases solubility, toxicity

15. Structures- Dendrimers

16. Structures- Nanoshells This category encompasses vesicular porous structures Typically Silica or Calcium Phosphate Minimum reliable pore size � 2 nm Materials can be trapped in interior space with nanoparticle �corks�, which can be actively targeting Alternately, structure may be biodegradable Drugs are released from internal cavities as structure erodes

17. Structures- Other Archaesomes Polar ether lipids from various bacteria Adapted to harsh conditions, i.e. high temperatures or low pH Longer stability, resistance to oxidation and other chemical degradation Cochleates Small, stable lipid structures Bilayer sheet rolled up in a spiral Enhanced stability, ability to deliver negatively or positively charged species Used for oral delivery

18. Other Structures- Cochleates

19. Research Focus Polymeric Liposomes Abundant research materials Other techniques in many case seem to be trying to imitate liposome efficacy while overcoming shortcomings