Health & Medicine Drug Delivery

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.

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.

What If? What if you never had to have another needle? Image: [email_address]

What If? What if you could prevent disease more easily in developing countries? Image: [email_address]

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. Image: [email_address]

“ 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.

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

What Is A Transdermal Patch? Delivery of drug/vaccine into skin Example of transdermal patch Images: Courtesy Nanotechnology Victoria Ltd, Resin[sistem] Design Definition–An adhesive patch containing micro sized needles that painlessly penetrate the skin to deliver nano-formulated drugs and vaccines. (This example developed by Nanotechnology Victoria)

Definition–An adhesive patch containing micro sized needles that painlessly penetrate the skin to deliver nano-formulated drugs and vaccines.

(This example developed by Nanotechnology Victoria)

Activity 1 Image: [email_address] Complete the Vaccination SWOT Analysis Activity to compare the strengths and weaknesses of conventional and transdermal methods of vaccination.

How Do Vaccines Work? Image: Sarah Keenihan 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). antigen lymphocytes lymph node APC skin

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).

How Do Vaccines Work? Image: © Dorling Kindersley 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 infection occurs, the memory cells are primed and ready to act and combat the infection e.g. produce antibodies specific to the antigen.

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 infection occurs, the memory cells are primed and ready to act and combat the infection e.g. produce antibodies specific to the antigen.

Animation Watch the Vaccination and Transdermal Patch Animations to improve your understanding of delivering vaccines and drugs via the skin.

Benefits Of Transdermal Patches Image: Courtesy Nanotechnology Victoria Ltd What are the benefits of transdermal delivery from a medical point of view?

Benefits Of Transdermal Patches Image: Courtesy Nanotechnology Victoria Ltd 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

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.

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.

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.

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.

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.

Nano-Formulated Vaccines Trigger An Optimal Immune Response Image: Courtesy Nanotechnology Victoria Ltd, based on data from Intersuisse Bioscience, 2006 Data was generated by vaccinating mice with various sized particles, and then counting the number of activated immune cells. Vaccine particle size Immune response (number of activated immune cells per million total cells) 0 30nm 100nm 500nm 1000nm

Advantages Of Transdermal Patches: Summary Image: pruzicka@flcikr 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 programs e.g. air-drop into disaster zones Suitable for veterinary purposes Biocompatible and biodegradable material used to make patches Can achieve short- & long-term delivery.

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 programs e.g. air-drop into disaster zones

Suitable for veterinary purposes

Biocompatible and biodegradable material used to make patches

Can achieve short- & long-term delivery.

Other Examples Of Transdermal Patches Image: andreas@flickr 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 contains nicotine - a selectively permeable membrane allows diffusion of nicotine into the skin.

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 contains nicotine - a selectively permeable membrane allows diffusion of nicotine into the skin.

Wearable Transdermal Patches Image: © Leah Heiss, 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

Transdermal patches could be incorporated into jewellery

This would be particularly beneficial for the transdermal delivery of drugs such as insulin.

Activity 2 Perform the Transdermal Patches Activity to gain an understanding of the history and development of transdermal patches.

Experiment 1 Transdermal Immunisation Perform the Modelling Transdermal Immunisation Experiment to better visualise this mode of delivering vaccines and drugs.

Designing Better Transdermal Patches Image: © Dorling Kindersley 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 Let’s examine the structure and function of human skin.

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

Let’s examine the structure and function of human skin.

Human Skin Image: alosojos@flickr 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.

Functions of skin:

A barrier against pathogens

A water proof coat

Contains melanin – a pigment that helps protect against UV radiation

Protects internal organs.

What Is Skin Made Of? Image: © Dorling Kindersley Epidermis – the outer most layer Dermis – holds the hair, muscles, blood supply, sebaceous glands, nerve receptors and fat. pore oil gland hair epidermis dermis subcutaneous layer erector pili muscle hair follicle blood vessels nerve sweat gland

Epidermis – the outer most layer

Dermis – holds the hair, muscles, blood supply, sebaceous glands, nerve receptors and fat.

Activity 3 & Experiment 2 Perform the Structure and Function of Skin Activity and/or the Skin Observation Experiment to learn more about skin.

Function Of Skin: Barrier Image: karlasfotos@flickr 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.

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.

Function Of Skin: Temperature Control Image: aliciayeah@flickr Humans have adaptations to help control temperature: Sweating Capillaries changing size Gooses bumps Shivering. Human body temperature is 37 °C The skin is critical in temperature control

Humans have adaptations to help control temperature:

Sweating

Capillaries changing size

Gooses bumps

Shivering.

Human body temperature is 37 °C

The skin is critical in temperature control

Temperature Control: Sweating Image: © Dorling Kindersley The skin’s 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. SOLID LIQUID GAS energy absorbed energy released

The skin’s 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.

Temperature Control: Vasodilation Image: linnybinnypix@flickr 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.

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.

Temperature Control: Goose Bumps Image: © Dorling Kindersley warm cold 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.

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.

Extended Learning Other examples of nanotechnology in medicine. HIV/AIDS: Dendrimers Teeth: Recaldent.

HIV/AIDS: Dendrimers

Teeth: Recaldent.

What If? What if you could stop the spread of HIV in the developing world? Image: [email_address] Photo taken outside a school in Zambia, Africa in 2005

HIV Prevention: Viva Gel TM Image: © StarPharma 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.

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.

HIV Infection Image: © StarPharma 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.

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.

How The Dendrimer Works Image: © StarPharma The dendrimer binds to proteins on the surface of the HIV virus. The virus can’t attach to the receptors on the human T cells. Infection is prevented.

The dendrimer binds to proteins on the surface of the HIV virus.

The virus can’t attach to the receptors on the human T cells.

Infection is prevented.

Tooth Repair: Recaldent Watch video: www. gcamerica.com A nano-modified milk protein that delivers Calcium and Phosphate to teeth to reform the tooth enamel. Recaldent was developed in Australia

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

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.

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.

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.

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.