May 08 2023

New Platform for Timed Drug Release

This is one of those technologies that most people probably never think about, but could potentially have a significant impact on our lives – timed drug release. The concept is nothing new, but there is a lot of room for improvement on current technologies. We already have time-release capsules, patches, and some drugs that can have long term effects with one dose, like Depo Provera. But for most drugs, you have to dose them every day at least.

Only about¬† 50% of people take their medication correctly, without missing doses. This has huge consequences, resulting in, “100,000 deaths, as much as 25% of hospitalizations, and a healthcare cost exceeding $100 billion” in the US alone. Right now we primarily deal with this problem through patient education and using drugs, when possible, that have longer dosing times. Sometimes we also monitor patient compliance with blood tests. There is also occasionally talk of developing a medicine bottle that monitors compliance (going back to at least 1989), but such technologies are not in widespread use.

There is therefore a lot of benefit that could potentially result from developing a drug delivery platform that can deliver a consistent dose of medication over weeks or even months. Imagine getting a shot every three months (perhaps even self-administered at home) rather than taking a pill every day. Researchers have recently published one potential such technology, they are calling PULSED – Particles Uniformly Liquified and Sealed to Encapsulate Drugs.

The idea is to seal doses of drug into small encapsulated beads, made from biodegradable material. Further, this material can be fine-tuned in order to precisely vary how long it will take to break down and release the drugs inside. The idea would be to contain in a single shot capsules that will break down over increasingly longer periods of time, dosing the drug at regular intervals. In order to be effective such technology must not only work, it needs to be scalable and cost effective, which the researchers claim is possible with this technology. They conclude:

The PULSED system is highly versatile, offering compatibility with crystalline and amorphous polymers, easily injectable particle sizes, and compatibility with several newly developed drug loading methods. Together, these results suggest that PULSED is a promising platform for creating long-acting drug formulations that improve patient outcomes due to its simplicity, low cost, and scalability.

Sounds great. Of course, as anyone who follows technology news knows, most new technologies don’t pan out, or take a lot longer to develop than initially projected. Also, they are rarely the panacea they are originally hyped to be, but might fill a needed niche at some point. So what are the prospects for this technology?

There will plausibly be a niche for this tech, if it does ultimately work in a cost-effective way. What we have now is essentially a proof of concept. One or more pharmaceutical companies will need to develop it further into a workable solution. But there are many potential hurdles to this actually working.

One of the trade-off for long acting medicine formulations is that the resulting dosing is variable.  You might technically be able to take one dose per day instead of 3 or 4, but the resulting blood levels will likely be more variable. For oral medication, this usually has to do with absorption. For the PULSED technology there will likely be variability in the dissolving time of the capsules. Imagine how consistent and predictable you need to be in order to have a steady release of drug every day over months.

This matters more for some drugs than others. For high blood pressure, for example, we need very steady dosing. Too much drug and your blood pressure can drop, causing light-headedness and even fainting. To little, and your blood pressure goes too high. For anti-seizure medication, if the blood levels drop too low you can have breakthrough seizures, which defies the entire purpose of this platform.

This platform would work best for drugs that already have a long half-life, because variability in dosing will have less of an effect on blood levels (which rise and fall slowly). It will also work well for drugs that have a high tolerance for variable blood levels. Antibiotics would likely be a great application – if you need to complete a 2-3 week course of antibiotics, for example, one shot may do the trick, and it avoids people stopping their regimen early once they feel better, reducing bacterial resistance. Nutrients also would be ideal for this platform, because variable dosing is not a problem within a very wide range, as long as the total dose over time is correct. A patient with low B12 could get a single shot and be good for 6 months or a year.

The platform is also being considered for vaccines that require multiple doses over weeks or a few months. The obvious benefit for this is to improve compliance. If also reduces the number of shots people need to get, and perhaps reduce overall side effects. This is particularly helpful in poorer countries where it is difficult to get people to make multiple trips to a clinic.

Another potential downside to long-term drug release is side effects. What if you develop side effects, or even an allergy, to a medication which is now going to be released into your system for three months? This means we would only use this option once someone has demonstrated that they tolerate and respond well to the drug, so they are on a stable drug regimen and likely will be for a long time.

I think the best way to look at developments like this is that is may provide another option, rather than replacing all existing options. Medical decision-making often comes down to risk vs benefit. This technology has its own risks and benefits, and in specific situations may be worth it overall. If it works out economically and the technology works well enough, hopefully it can eat into the costs of medicine non-compliance, which are significant.

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