Managing complex medication schedules, a challenge faced by millions of patients worldwide, could soon become significantly simpler. Imagine a future where the intricate routine of taking multiple pills at different times of the day is reduced to swallowing a single capsule in the morning. Exactly such an innovation is being developed by engineers at the University of California, San Diego (UC San Diego), creating a revolutionary capsule capable of storing multiple different medications and releasing them precisely at predetermined time intervals throughout the day.

This significant achievement, detailed in the scientific journal Matter, promises a radical change in the way patients approach therapy. By eliminating the need to remember taking different medications or doses at specific times, this smart capsule has the potential to drastically improve adherence to prescribed therapy. Consequently, better health outcomes are expected, reducing the risk of missed doses that can diminish treatment effectiveness, as well as the dangers of accidental overdose.

Smart Technology for Simplified Treatment

"Our goal is to simplify medication management with a single capsule that is 'smart' enough to deliver the right drug, at the right dose, and at the right time," explains Dr. Amal Abbas, the first author of the study who recently earned her Ph.D. in chemical engineering from the Jacobs School of Engineering at UC San Diego. Dr. Abbas led this project in collaboration with Joseph Wang, a distinguished professor in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at UC San Diego. Recognizing the enormous potential of this technology for patients and their caregivers, Dr. Abbas is launching a startup company to accelerate the further development and commercialization of this innovative capsule.

The core of the innovation lies in the capsule's internal structure. Multiple different drugs are packaged into separate compartments within a single shell. Each compartment is designed to release its contents at a precisely defined moment. The key element enabling this are the barriers separating the drugs. These barriers are made from a matrix of lactose and maltose embedded with a polymer sensitive to the pH value of the environment. This smart polymer acts as a shield, protecting the drugs from the acidic environment of the stomach, but dissolves when it reaches the more alkaline environment of the small intestine. By precisely adjusting the density of this polymer, researchers can control the time required for each barrier to dissolve, thus ensuring that the drugs are released at precisely timed intervals after taking the capsule.

Innovative Release Mechanisms

The outer shell of the capsule consists of a body and a cap, made from vegetable cellulose, a material widely accepted in the pharmaceutical industry. The main body of the capsule, housing the compartments with drugs, is protected by the aforementioned pH-sensitive polymer. On the other hand, the capsule cap lacks this protection. It dissolves as soon as the capsule reaches the stomach, triggering the immediate release of the first drug from its corresponding compartment.

However, precise timing is not the only advanced feature of this capsule. The research team has also incorporated microscopic magnesium particles that act as tiny, temporary "micro-stirrers" within the body. These particles react with stomach acid (hydrochloric acid, HCl), generating hydrogen bubbles (H2). The release of these gaseous bubbles creates gentle movement that mixes the capsule's contents. This micro-mixing enhances drug dissolution, which is particularly useful for drugs requiring rapid absorption, such as analgesics, cardiovascular medications, or emergency therapies.

The magnesium particles also have another important function: through chemical reaction, they neutralize stomach acid in the immediate vicinity of the capsule. This temporarily creates a localized alkaline micro-environment. This increase in pH value helps dissolve the pH-sensitive polymer barriers separating the remaining compartments, thereby initiating the sequential release of the subsequent drugs in the series.

Pioneering Work in the Field of Microrobots

"This innovative single-daily-capsule approach ensures full-day and complete adherence to therapy, leading to improved patient outcomes," highlights Professor Wang. His research group is a world leader in using micron-sized particles – which they termed microrobots – for therapeutic purposes. They were the first to successfully apply microrobots in live animal models, demonstrating their potential in treating various conditions, including lung infections and diseases requiring intensive care. Their extensive experience with microrobots laid the foundation for integrating similar technology into this time-controlled release capsule.

An important aspect for future application is the fact that all materials used to make the capsule are approved by the U.S. Food and Drug Administration (FDA). "This will help ensure an easier transfer of the technology to the market and faster availability to patients," emphasizes Dr. Abbas.

Proof of Concept and Potential Applications

As a proof-of-concept, the researchers filled the capsule with three doses of levodopa, a medication used to treat Parkinson's disease. Each dose was labeled with a different food coloring – yellow, green, and red – to visually track its release under simulated stomach conditions. The first dose, placed in the compartment containing magnesium micro-stirrers, was designed for rapid release. The second and third doses, placed in compartments without stirrers, were released at medium and slow rates, respectively. The experiment successfully demonstrated that the capsule can deliver drugs in different, predefined phases.

The choice of a Parkinson's disease drug as a test case was not coincidental. Treating this disease requires consistent medication intake every few hours to keep symptoms under control. Fluctuations in drug levels can lead to the so-called "on-off" phenomenon, with periods of good mobility ("on") and periods of stiffness and tremor ("off"). "This time-controlled release of multiple doses could really help patients with Parkinson's disease," says Dr. Abbas. "If the drug level drops too low, patients will experience tremors and other motor symptoms. But if we can keep that level stable, we can also help maintain the stability of the patient's movement. Our capsule has the potential to provide that stability throughout the day – so patients don't have to worry about perfectly timing each dose."

Wide Spectrum of Possibilities

Dr. Abbas also sees great potential in using this capsule for combination therapies. Cardiovascular diseases, for example, often require patients to take a combination of drugs such as aspirin, beta-blockers, and cholesterol-lowering drugs (statins) – each with its own recommended dosing schedule. By customizing the capsule compartments to release these drugs in a precisely timed sequence, patients could receive their aspirin in the morning, beta-blocker in the afternoon, and cholesterol medication in the evening – all from a single capsule. Such an approach could ensure that each drug is delivered at the time it is most effective, potentially reducing side effects and optimizing therapeutic benefits.

Problems with therapy adherence represent a global health challenge. It is estimated that a significant percentage of patients with chronic diseases do not adhere to prescribed treatment regimens, leading to poorer health outcomes, increased hospitalization rates, and significant costs to the healthcare system. The complexity of regimens, forgetfulness, drug side effects, and a lack of understanding of the therapy's importance are just some of the factors contributing to this problem. Solutions like this smart capsule offer a concrete technological response to the challenge of improving adherence.

Future Steps and Challenges

The next steps in developing this technology include conducting in vivo testing in animal models, followed by clinical trials in humans to confirm safety and efficacy under real-world conditions. Methods for mass production (scaling up) also need to be developed to make the capsule affordable. The team is also exploring possibilities to extend the capsule's release capability beyond a single day, which would be beneficial for medications taken less frequently. Additionally, the potential for localized drug release within the digestive system is being investigated, which could enable targeted therapies for specific parts of the intestine, for example, in inflammatory bowel diseases.

Despite the promising results, the technology also faces challenges. Ensuring consistent release profiles in the variable environment of the human digestive system, adapting to individual differences among patients, and achieving cost-effectiveness in mass production will be key to the successful commercialization and widespread adoption of this advanced drug delivery technology.

Source: University of California