HEALTH & MEDICINE - DRUG DELIVERY * Image courtesy of

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HEALTH MEDICINE - DRUG DELIVERY
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MODULE OUTCOMES

• Have an understanding of vaccination
• Investigate the structure and functions of skin,
  and how vaccines/drugs are delivered through it
• Understand why transdermal patches offer
  advantages over current immunisation practises
• Identify recent developments in nanotechnology
  and how they impact on vaccination strategy and
  other health outcomes.

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WHAT IF?

• WHAT IF YOU NEVER HAD TO HAVE ANOTHER NEEDLE?

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WHAT IF?

• WHAT IF YOU COULD PREVENT DISEASE MORE EASILY IN
  DEVELOPING COUNTRIES?

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DID YOU KNOW?

• A young person with Type 1 diabetes will use up
  to 1500 syringes a year - Associate Professor
  John Fitzgerald, School of Population Health,
  University of Melbourne, July 2007
• Globally, around 30 billion syringes are used per
  year 800 million are used by Australians.

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WHAT IF?

• What if there was an alternative to needles for
  delivery of vaccines and drugs like insulin?

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WHAT IS A TRANSDERMAL PATCH?
Delivery of drug/vaccine into skin
Example of transdermal patch

• DefinitionAn adhesive patch containing micro
  sized needles that painlessly penetrate the skin
  to deliver nano-formulated drugs and vaccines.
• (This example developed by Nanotechnology
  Victoria)

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ACTIVITY 1
Complete the Vaccination SWOT Analysis Activity
to compare the strengths and weaknesses of
conventional and transdermal methods of
vaccination.
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HOW DO VACCINES WORK?

• Vaccines deliver antigens to the skin or blood
  stream antigens are fragments of infectious
  agents
• The antigen is gobbled up by an antigen
  presenting cell (APC)
• The APC travels to a lymph node where it
  interacts with lymphocytes (a type of immune
  cell).

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HOW DO VACCINES WORK?

• In the lymph node, specific lymphocytes targeted
  at the antigen in the vaccine are produced-
  these cells persist in the body as memory cells
• Then if an actual infectionoccurs, the memory
  cells are primed and ready to act and combat the
  infectione.g. produce antibodies specific to the
  antigen.

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ANIMATION
Watch the Vaccination and Transdermal Patch
Animations to improve your understanding of
delivering vaccines and drugs via the skin.
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BENEFITS OF TRANSDERMAL PATCHES
What are the benefits of transdermal delivery
from a medical point of view?
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BENEFITS OF TRANSDERMAL PATCHES

• Protrusions can be specifically engineered to
  ensure
• Delivery directly to immune cells therefore less
  material required
• Painless application and no scar tissue formation
• Versatility in applications vaccines, drugs,
  hormones, wound healing proteins.

Microscopic images of transdermal patch
protrusions
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BENEFITS OF TRANSDERMAL PATCHES

• Transdermal patches can deliver nano-formulated
  drugs/vaccines, which- have unique properties-
  can easily enter blood vessels once delivered to
  skin- can target particular cell types, such as
  immune cells
• Examples of drugs that could be patch-delivered
  - proteins such as insulin
• Examples of vaccines that could be patch
  delivered- protein vaccines- DNA vaccines.

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BENEFITS OF TRANSDERMAL PATCHES

• Due to directed delivery of nano-formulated
  drugs/vaccines, the use of patches means that-
  only small quantities of drugs/vaccines are
  required- less drug/vaccine is wasted i.e.
  dispersed in blood or connective tissue before it
  reaches target cells- less side effects due to
  small dosage delivered directly to target cells
  - an optimal immune response is generated.

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NANO-FORMULATED VACCINES TRIGGER AN OPTIMAL
IMMUNE RESPONSE
Data was generated by vaccinating mice with
various sized particles, and then counting the
number of activated immune cells.
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ADVANTAGES OF TRANSDERMAL PATCHES SUMMARY

• Delivery of nano-sized particles directly to the
  immune system
• Delivery of molecules that normally cannot
  penetrate the skin
• Lower dosages less side effects
• Easy to use, no needle-stick injury, low risk of
  infection, pain-free
• Can be self-administered, or given by a
  non-medical person
• Smaller, lighter, lower transport cost
• Mass production cost benefits
• Suitable for public health programse.g. air-drop
  into disaster zones
• Suitable for veterinary purposes
• Biocompatible and biodegradable material used to
  make patches
• Can achieve short- long-term delivery.

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OTHER EXAMPLES OF TRANSDERMAL PATCHES

• In addition to Nanotechnology Victoria, other
  groups within Australia are working on
  transdermal patches eg Dr Mark Kendall at AIBN,
  Queensland- developing a micro-nano projection
  array patch (Nanopatch)- could be used for
  vaccination or DNA delivery- vaccine/DNA
  molecules are dry-coated on to the patch
  projections for delivery to target cells through
  the top layer of skin (epidermis)
• Nicotine patches (to help smokers quit)- plastic
  chamber within patch containsnicotine- a
  selectively permeable membrane allows diffusion
  of nicotine into the skin.

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WEARABLE TRANSDERMAL PATCHES

• Transdermal patches could be incorporated into
  jewellery
• This would be particularly beneficial for the
  transdermal delivery of drugs such as insulin.

Insulin-dispensing rings designed by
Nanotechnology Victoria Artist in Residence Ms
Leah Heiss
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ACTIVITY 2
Perform the Transdermal Patches Activity to gain
an understanding of the history and development
of transdermal patches.
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EXPERIMENT 1 TRANSDERMAL IMMUNISATION
Perform the Modelling Transdermal Immunisation
Experiment to better visualise this mode of
delivering vaccines and drugs.
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DESIGNING BETTER TRANSDERMAL PATCHES

• To design better patches and drugs/antigens,
  scientists need to understand skin
• For example, certain drugs can penetrate
  particular layers of the skin more effectively
  than others
• Lets examine the structure and function of
  human skin.

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HUMAN SKIN
THE SKIN IS THE LARGEST AND HEAVIEST ORGAN OF THE
BODY.

• Functions of skin
• A barrier against pathogens
• A water proof coat
• Contains melanin a pigment that helps protect
  against UV radiation
• Protects internal organs.

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WHAT IS SKIN MADE OF?

• Epidermis the outer most layer
• Dermis holds the hair, muscles, blood supply,
  sebaceous glands, nerve receptors and fat.

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ACTIVITY 3 EXPERIMENT 2
Perform the Structure and Function of Skin
Activity and/or the Skin Observation Experiment
to learn more about skin.
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FUNCTION OF SKIN BARRIER

• Skin cells are being replaced 24/7
• New cells are made in the lower epidermis by cell
  division
• New cells move towards the surface to replace old
  cells
• Old cells die and flake off
• In the epidermis the cells become flatter and
  keratinized making them tough and water proof.

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FUNCTION OF SKIN TEMPERATURE CONTROL

• Human body temperature is 37C
• The skin is critical in temperature control

• Humans have adaptations to help control
  temperature
• Sweating
• Capillaries changing size
• Gooses bumps
• Shivering.

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TEMPERATURE CONTROL SWEATING

• The skins temperature receptors sense the
  external temperature change and send a signal to
  the brain
• Brain sends a message for the skin to produce
  sweat
• Energy (heat) needed to change liquid water to
  gas
• Sweat evaporates and cools the body down.

energy absorbed
SOLID
LIQUID
GAS
energy released
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TEMPERATURE CONTROL VASODILATION

• Blood in the skin has a network of small
  capillaries
• When you are cold, the muscles around capillaries
  constrict, capillaries become narrow, less blood
  passes to the surface and less heat is lost
• When hot, the muscles around capillaries relax,
  more blood passes to the surface and more heat
  passes to the skin surface.

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TEMPERATURE CONTROL GOOSE BUMPS

• When you are cold the muscles around the hairs in
  the skin contract and the hairs become erect
• Hairs trap a layer of warm air
• Reduces heat loss.

warm
cold
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EXTENDED LEARNING
OTHER EXAMPLES OF NANOTECHNOLOGY IN MEDICINE.

• HIV/AIDS Dendrimers
• Teeth Recaldent.

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WHAT IF?
What if you could stop the spread of HIV in the
developing world?
Photo taken outside a school in Zambia, Africa in
2005
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HIV PREVENTION VIVA GELTM

• Viva Gel contains active ingredients called
  dendrimers
• Viva Gel is used at the skin surface to prevent
  viral infection
• Dendrimers are branched, nanosized molecules with
  specific known properties and are tailor made for
  a specific purpose.

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HIV INFECTION

• The HIV virus (yellow and purple) infects human
  T-cells (pink) by attaching to receptors on the
  surface of the T-cell (an important immune cell)
• The virus then enters the T cell and reproduces
  inside it
• The virus kills the T cells causing the person to
  lose immunity.

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HOW THE DENDRIMER WORKS

• The dendrimer binds to proteins on the surface of
  the HIV virus.
• The virus cant attach to the receptors on the
  human T cells.
• Infection is prevented.

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TOOTH REPAIR RECALDENT

• A nano-modified milk protein that delivers
  Calcium and Phosphate to teeth to reform the
  tooth enamel.

Recaldent was developed in Australia
Watch video www.gcamerica.com
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SUMMARY

• Transdermal patches incorporating nanotechnology
  can be utilised for vaccine and drug delivery via
  the skin
• Nanotechnology Victoria is developing transdermal
  patches for drug delivery
• Designing and understanding how vaccines work
  requires an appreciation of the structure and
  function of skin.

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REVISION

• Why are scientists interested in transdermal drug
  delivery?
• How does vaccination work?
• Apart from vaccines, what other substance could
  be delivered through the skin?
• Describe the functions of human skin.

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HEALTH MEDICINE - DRUG DELIVERY