Nano-scale Drug Delivery Modern Structures and Materials

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Nano-scale Drug DeliveryModern Structures and
Materials

• ECE 510 30April2008
• Ed Katz

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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

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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

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Long circulation time- Particle size

• Small particles (lt10 nm) are lost to
  extravasation (absorption into tissue)
• Large Particles (gt200 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

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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

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Structures

• Nanocapsules
• Nanotubes
• Nanogels
• Dendrimers
• Nanoshells
• Other Structures

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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

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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
  userkosigrim)

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Liposome Micelles in Practice
FIGURE 1 Effect of the hydrophobic molecule
on the morphology of the micelles. (a) 10 wt.
F127, (b) 10 wt. F127 with 0.2 wt.
Haloperidol. Lam, Y.M., Goldbeck-Wood, G.,
Boothroyd, C., 2003. Mesoscale Simulation and
Cryo-TEM of Nanoscale Drug Delivery Systems.
Molecular Simulation. Vol 30, No. 4, pp 239-247.
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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

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Nanotubes in practice
Field emission scanning electron micrographs
(FESEM) of a home-made alumina template (60-nm
diameter) after silica surface solgel
template synthesis top-viewed (left) and
cross-sectional viewed image (right).
The cross-sectionally viewed image reveals that
silica nanotubes were synthesized within the
pores of the template. Son, S., Bai, X., Lee,
S., 2007. Inorganic Hollow Nanoparticles and
Nanotubes in Nanomedicine Part 1. Drug/Gene
deliver applications. Drug Discovery Today. Vol
12, No. 15/16, pp 650-656.
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Structures- Nanogels

• Can be synthesized and stored without drugs,
  subsequently loaded
• Extended stability
• Low Toxicity
• Limited methods for surface coating

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Structures- Nanogels
Goldberg, M., Langer, R., Jia, X., 2007.
Nanostructured Materials for applications in Drug
Delivery and Tissue Engineering. J. Biomater.
Sci. Polymer Edn. Vol 18, No. 3, pp 241-268.
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Structures- Dendrimers

• Controlled shape
• Relatively easy to isolate
• Drugs can be enveloped by structure or bonded
  to branches
• Increasing size increases solubility, toxicity

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Structures- Dendrimers
Diagram by Oleg Lukin
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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

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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

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Other Structures- Cochleates
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Research Focus

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