Health & MedicineDrug 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.

What If?What if you never had to have another needle?

Image: ninjapoodles@flickr

What If?What if you could prevent disease more easily in developing countries?

Image: hdptcar@flickr

Did You Know?

Image: 42dreams@flickr

• “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 skinExample 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)

Activity 1

Image: hmk@flickr

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

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 infectionoccurs, the memory cells are primed and ready to act and combat the infectione.g. produce antibodies specific to the antigen.

AnimationWatch 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

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.

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.

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.

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 containsnicotine- 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

Activity 2Perform 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.

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.

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

hairepidermis

dermis

subcutaneous layer

erector pili muscle

hair follicle

blood vessels

nerve

sweat gland

Activity 3 & Experiment 2Perform 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.

Function Of Skin: Temperature Control

Image: aliciayeah@flickr

Humans have adaptations to help control temperature:

1. Sweating2. Capillaries changing size3. Gooses bumps 4. 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

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.

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.

Extended LearningOther examples of nanotechnology in medicine.

• HIV/AIDS: Dendrimers• Teeth: Recaldent.

What If?What if you could stop the spread of HIV in the developing world?

Image: london@flickr

Photo taken outside a school in Zambia, Africa in 2005

HIV Prevention: Viva GelTM

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.

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.

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.

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

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.

Revision1. Why are scientists interested in

transdermal drug delivery?2. How does vaccination work?3. Apart from vaccines, what other

substance could be delivered through the skin?

4. Describe the functions of human skin.