Wearable drug delivery systems, also known as on-body systems, are designed to accurately deliver the right dose of a drug to the right place at the right time, via a pump and cannula or needle, or a drug delivery patch. These can be particularly useful for chronic diseases needing regular treatment in the long-term, such as diabetes, ocular disorders, cancer, and cardiovascular disease, or for a condition that needs a longer bolus delivery, such as wound healing. They can deliver a large volume over a long period, and/or specific doses at specific times. 

Wearable delivery systems range from smart patches to pumps that are worn on a strap or adhere to the skin, and include microelectromechanical systems (MEMS). These are miniaturised integrated devices that combine electrical and mechanical components, and may be powered or non-powered. Wearable systems can incorporate sensors or link to smartphones. [1-6]

A wearable drug delivery device will include some or all of the following components: [3, 7]

●A method to wear the device or attach it to the body

●A route for the drug (channels or tubes) 

●A pump

●A drug reservoir

●A needle insertion system

●A needle or soft cannula

●A power source

●Sensors

●Electronics.

The connected drug delivery devices market size is growing - it is expected to be worth $1.18 billion in 2024, rising to $5.30 billion in 2029 (CAGR of 35.13%). [8]

Benefits and challenges 

Some drugs, including biologics, have to be delivered as subcutaneous, intramuscular or intravenous injection. [9] Intravenous drug delivery requires patients to attend a hospital or clinic, which can be inconvenient and raises the costs because of requirements for staff and clinic space. While self-injection devices allow patients to administer their own drugs at home, patients with poor manual dexterity or who have issues with anxiety can struggle with self-injection. Anxiety can also increase the perception of pain. These factors have an impact on adherence, and poor adherence is associated with up to 69% of routine hospitalisations in the US. In addition, the manufacturing, shipping and disposal of single use injection devices has environmental implications. [2, 10] 

A wearable drug delivery system makes treatment easier and more convenient for the patient, reduces the need for clinic or hospital visits, takes away the anxiety involved in self-injection, improves adherence and reduces errors and waste. Closed loop drug delivery systems allow doses to be tailored to the patient's needs. As well as supporting the systemic delivery of biologics, wearables can deliver drugs locally, for example to the eye, reducing the concerns associated with systemic toxicity and allowing the drug to be delivered across biological barriers. [6, 7, 11]

Companies need to be aware of certain issues when developing and manufacturing wearable delivery systems. The skin underneath a wearable device, particularly one that sticks to the skin, can become irritated by sweat or ingredients in adhesives, or as a result of contact with the metallic or synthetic materials making up the device. [1] Also, the power sources can generate heat, causing discomfort. [5]

Anything that is worn on or close to the body for an extended period of time must be safe. Manufacturers need to adhere to safety, regulatory and certification guidelines in order to get their products onto the market. Requirements will vary according to location but may include: [6, 7, 12]

●Dosing and dose delivery profiles

●Adhesive properties (for patch-based systems)

●Needle/cannula insertion distance

●Behaviour under environmental conditions

●Electrical safety testing

●Battery safety testing

●Specific absorption rate (SAR) testing

●Biocompatibility

●Data security, both in the device and in the cloud

●Electromagnetic compatibility (EMC)

●Usability

●Wireless device testing.

Closed loop systems

Closed loop drug delivery systems combine diagnostics, real-time monitoring and on-demand drug delivery. [13] 

The sensors in a closed loop system can detect a variety of biomarkers, including temperature, pulse, respiration, metabolites, blood flow, oxygenation, sleep patterns, pain and pH (wound healing). They can also detect when an epileptic seizure is about to happen. The data collected can be analysed in real time, which allows rapid treatment, improving patient outcomes and quality of life, and reducing the need for in-hospital treatment. [5] To be effective, the sensors and the delivery system must be closely integrated and able to communicate with each other efficiently and effectively. [14]

The best-known closed loop systems are those for insulin delivery in diabetes, known as artificial pancreases. These closed loop systems were pioneered in the 1960s and 1970s, but have become smaller, more accurate and more reliable over the years. The current hybrid closed loop systems, available since 2016, aim to reduce episodes of hypoglycaemia and hyperglycaemia and maintain glucose levels within a target range. They combine a pump with sensors, and use algorithms to both adjust the basal rate of insulin delivery, and administer bolus doses as needed. User input is required for mealtime boluses. Fully closed loop systems are in development but the challenge for these is to deal with the doses required at mealtimes without the user inputting information on carbohydrate content. [15]

Other potential applications for pump-based closed loop systems include a device that monitors patients during chemotherapy, personalising the dose based on the concentration of the drug in their system. [16]

Smart patches are closed loop systems that adhere closely to the skin, and combine biosensing with a delivery system that delivers drugs transdermally or subcutaneously (via microneedles). Smart contact lenses, which combine a delivery system, a sensor, wireless power and communications, and an integrated circuit chip, have potential for the on-demand and/or long-term treatment of chronic eye disease. These, however, can only deliver small volumes of drug. [17-19]

Looking to the future

The power source for a wearable is a limiting factor, as it needs to be small, and so will need regular recharging or replacing. Renewable energy sources, including biomechanical (body movements), biochemical (sweat, urine and other body fluids), and biothermal (temperature differences between the body and the environment) energy, would improve the flexibility of the technology. [13]

Wearable drug delivery systems will evolve to carry larger volumes and deal with drugs with increased viscosity or that require more complex dose preparation. [20]

References

1. Staff writer, The trend towards wearable drug delivery systems. Micro Systems Insights, 27 June 2023. Available from: https://www.medicalmoulds.com/the-trend-towards-wearable-drug-delivery-systems/.

2. Kar, A., et al., Wearable and implantable devices for drug delivery: Applications and challenges. Biomaterials, 2022. 283: p. 121435.

3. Kirchbach, A., The Challenge of Developing Wearable Drug Delivery Devices. Raumedic Insights, 4 April 2023. Available from: https://www.raumedic.com/insights/the-challenge-of-developing-wearable-drug-delivery-devices.

4. Elvidge, S., Microelectromechanical systems (MEMS) in drug delivery. Pharma Sources, 17 May 2024. Available from: http://www.wdnpy.cn/industryinsights/microelectromechanical-systems-mems-in-d-76399.html.

5. Manikkath, J. and J.A. Subramony, Toward closed-loop drug delivery: Integrating wearable technologies with transdermal drug delivery systems. Adv Drug Deliv Rev, 2021. 179: p. 113997.

6. Berry, C. and G. Wynne, The Future of On-Body Medical Delivery Systems. Smithers, September 2023. Available from: https://www.smithers.com/en-gb/resources/2023/september/the-future-of-on-body-delivery-systems.

7. Staff writer, On the Rise: Wearable Injector Systems. Medical Design Briefs, 1 September 2021. Available from: https://www.medicaldesignbriefs.com/component/content/article/39771-on-the-rise-wearable-injector-systems.

8. Staff writer, Connected Drug Delivery Devices - Market Share Analysis, Industry Trends & Statistics, Growth Forecasts (2024 - 2029). Mordor Intelligence. 2024. Available from: https://www.giiresearch.com/report/moi1445686-connected-drug-delivery-devices-market-share.html.

9. Irvine, D., X. Su, and B. Kwong, Routes of Delivery for Biological Drug Products, in Pharmaceutical Sciences Encyclopedia. 2013. p. 1-48.

10. Antalfy, A., et al., The Adherence and Outcomes Benefits of Using a Connected, Reusable Auto-Injector for Self-Injecting Biologics: A Narrative Review. Adv Ther, 2023. 40(11): p. 4758-4776.

11. Kania, K., On-Body Drug Delivery System Reduces User Error & Waste. Packaging Digest, 27 December 2023. Available from: https://www.packagingdigest.com/drug-delivery-devices/on-body-drug-delivery-system-reduces-user-error-waste.

12. Staff writer, Keeping Wearable Technology Safe at Any Speed. UL Solutions, 26 January 2024. Available from: https://www.ul.com/insights/keeping-wearable-technology-safe-any-speed.

13. Zhang, G., et al., Bioenergy-Based Closed-Loop Medical Systems for the Integration of Treatment, Monitoring, and Feedback. Small Science, 2023.

14. Ghanim, R., et al., Communication protocols integrating wearables, ingestibles, and implantables for closed-loop therapies. Device, 2023. 1(3): p. 100092.

15. Templer, S., Closed-Loop Insulin Delivery Systems: Past, Present, and Future Directions. Front Endocrinol (Lausanne), 2022. 13: p. 919942.

16. Trafton, A., A closed-loop drug-delivery system could improve chemotherapy. MIT News, 24 April 2024. Available from: https://news.mit.edu/2024/closed-loop-drug-delivery-system-could-improve-chemotherapy-0424.

17. Khadka, B., B. Lee, and K.T. Kim, Drug Delivery Systems for Personal Healthcare by Smart Wearable Patch System. Biomolecules, 2023. 13(6).

18. Kim, T.Y., et al., Smart contact lens systems for ocular drug delivery and therapy. Adv Drug Deliv Rev, 2023. 196: p. 114817.

19. Kim, T.Y., et al., Wireless theranostic smart contact lens for monitoring and control of intraocular pressure in glaucoma. Nat Commun, 2022. 13(1): p. 6801.

20. Parker, M., K. Chellappan, and D. Cottenden, DIRECTIONS FOR WEARABLE ON-BODY INJECTOR SYSTEMS AND BEYOND. ONdrugDelivery, 10 September 2023. Available from: https://www.ondrugdelivery.com/directions-for-wearable-on-body-injector-systems-and-beyond/.

About the Author:

Suzanne Elvidge

Based in the north of England, Suzanne Elvidge is a freelance medical writer with a 30-year experience in journalism, feature writing, publishing, communications and PR. She has written features and news for a range of publications, including BioPharma Dive, Pharmaceutical Journal, Nature Biotechnology, Nature BioPharma Dealmakers, Nature InsideView and other Nature publications, to name just a few. She has also written in-depth reports and ebooks on a range of industry and disease topics for FirstWord, PharmaSources, and FierceMarkets. Suzanne became a freelancer in 2006, and she writes about pharmaceuticals, consumer healthcare and medicine, and the healthcare, pharmaceutical and biotechnology industries, for industry, science, healthcare professional and patient audiences.