"Advances in Implantable Drug Delivery Devices: A Breakthrough in Ultrasoft Balloon-Type Implants"

-DGIST Professor Kim Sohee's research team has successfully developed an Ultrasoft and flexible balloon-type implantable device for long-term drug delivery at the site of implantation-

-It is expected to be used for patients with chronic diseases such as cancer, diabetes, epilepsy, and diseased heart, as well as stem cell delivery for regenerative purposes-

Professor Sohee Kim's research team has successfully developed an Ultrasoft and flexible balloon-type implantable device for long-term drug delivery at the target site of implantation. As the developed device facilitates long-term controlled release with minimum foreign body responses, it is expected to be used for patients with chronic diseases such as cancer, diabetes, epilepsy and diseased heart as well as stem cell delivery for regenerative purposes.

We often listen these complains in our day-by-day life such as” Oh I forgot my medicines” or “I have needle phobia” or “toxic drugs killing me before the cancer does” are the common problems with systematic drug administrations. With systematic methods, you're shooting medicine into the body, hoping it hits the right spot. But implantable devices are more precise tools, delivering the drug right to where it's needed without all the guesswork. For this reason, Implantable devices are becoming more important because they offer a bunch of cool benefits. First of all, they deliver medication exactly where it's needed, which means less chance of side effects since it's not floating around your whole body. Plus, you don't have to worry about remembering to take your meds every day because these devices do it for you, like a little drug-dispensing buddy under your skin.

In the realm of implantable drug delivery devices, there exist primarily two classifications: biodegradable and non-biodegradable implants. Biodegradable implants necessitate a singular surgical procedure for insertion, gradually releasing medication as they degrade within the body. However, these implants are subject to influences from physiological variables such as temperature, pH levels, enzymatic degradation, and other physicochemical factors, potentially yielding varying outcomes among patients implanted with the same device. Moreover, their characteristic rapid initial drug release, accounting for 60-80% of the total dosage within a week, may effetc their longevity and give rise to local toxicity post-implantation.

Conversely, non-biodegradable devices, which dispense drugs from a reservoir via mechanisms such as diffusion, osmosis, or active delivery modulated by external stimuli, necessitate two surgical interventions—one for implantation and another for removal post-treatment completion. Nevertheless, they are typically engineered to remain chemically inert and stable within the physiological environment. Drug release from these devices tends to be more controlled and uniform, affording the ability to modulate release parameters such as kinetics, rate, and duration of operation in accordance with individualized treatment regimens. Nevertheless, a significant issue impacting the effectiveness of these devices arises from what is known as the foreign body response. This reaction leads to the formation of a fibroblast encapsulation around the device, essentially creating a tight tissue capsule. Consequently, all the drug released from the device becomes trapped within this capsule, thereby constraining the sustained and controlled release of medication.

To overcome the limitations of existing non-biodegradable devices, Prof. Kim’s research team developed an ultrasoft implantable device using a rubbery, elastic material that is considerably softer than plastic polymers along with optimized design with spherical and balloon shape, that minimizes the fibroblast encapsulation around the developed device.

The release was mainly modulated by the composition and thickness of soft polymer membrane. Various release kinetics profiles were achieved by changing the membrane thickness and composition. We were able to achieve a sustained release of drug for up to more than 5 months and all the devices were intact during this duration despite of the ultrasoft mechanical properties. During implantation, both in rats and nude mice, the device maintained a uniform release. Most importantly, the ultrasoft mechanical properties of the device ensured less foreign body responses than previously developed reservoir-type devices, with relatively thin fibrotic encapsulation.

The potential applications for our developed device are broad, including long-term drug release in models of diabetes, epilepsy, diseased heart and cancer as well as stem cell delivery for regenerative purposes. Our device fabrication technique offers unique advantages. It allows for the fabrication of sensors embedded in the drug delivery device itself. These sensors can serve as disease-specific biomarkers, such as pH, temperature, glucose and pressure sensors, facilitating real-time monitoring at the target site.

This study has been published in Biomaterials Research, a prestigious academic journal in the field of Biomedical Engineering (IF: 11.3, JCR top 4.7%). Tausif Muhammad, a Ph.D. student in the Department of Robotics and Mechatronics Engineering at DGIST, is the first author of the study.

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https://www.dgist.ac.kr/prog/bbsArticle/BBSMSTR_000000000188/view.do 

BRIC:

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