Drug delivery

Drug delivery

When you’re sick with headache or flu, you likely reach for the aspirin and the Tylenol. At your lowest point. When you feel like things can’t get any worse. With your head pounding. Your nose running a marathon. You reach for pills.

You don’t even think about it. But, culturally, it is ingrained in us. Pills are medicine.

This is something every supplement maker in the world is all too happy to jump on. Your nutritional supplement of choice, whether that’s multivitamins, cod liver oil or anything else comes in pill format. It doesn’t matter if it has any benefit for you, because the instinctively *feel *better for it.

A tablet or two, a sip of water and your health is taken care of. What happens then in the background is synonymous with magic. It doesn’t matter how the magician performs his trick, so long as you’re amazed at the end.

There is one obvious exception. That’s when you need to give medication to kids. Speaking as someone that took soluble paracetamol into his university years, taking pills, especially as a kid, can be hard. Convincing young kids and toddlers to take their medicine can sometimes feel like World War III. At times like these, it can be a real relief to see medication that comes as gummy bears or a sugary syrup.

In any case, the principle is the same. You are consuming medicine. It goes in the mouth, it gets swallowed, it has to survive the stomach acid, it has to survive the basic (as in alkaline) small intestine and then. Only then. Does it actually get absorbed into the body and into the blood.

The likes of Advil and Nurofen like to advertise their products as “fast acting”. Nurofen Express even comes as “liquid capsules” which their website tells us

“Liquid Capsules are absorbed faster than standard ibuprofen”

Are they though? They’re still going to sit in your stomach anywhere between 20 minutes to 6 hours depending on what you’ve eaten. The liquid capsules might release the ibuprofen for absorption a little quicker than a normal pill takes to dissolve. But really, the getting absorbed step, is not the slow part of the process. Bragging that you can sprint 100 metres really fast, doesn’t mean you’re going to finish the marathon.

The interesting thing is that many drugs are sold in this way. They promise fast relief, and yet, use an inherently slow method of getting in the body.

A smoker that *needs *a nicotine hit, doesn’t throw some raw tobacco in their mouth, then kick back and chill for an hour while the tobacco makes it way through their gut.


No. A much faster way of getting that nicotine into your body is to vapourise it by burning the tobacco and then rolling it around your lungs. From your lungs it is only a quick stop up the carotid artery to the brain. Total time from lips to lungs and on to the brain, is a matter of seconds.

Of course, not all drugs are going to be suitable to be vapourised. But, if the drug is nicely soluble, as most that come in pill format are, there is another obvious option.

You see, drugs don’t have to be put in at the top.

You gotta start at the bottom

Most people don’t like to think about it, but suppositories, both rectal and vagina are an easy alternative. In fact, it’s a pretty well-known method for cocaine use. Suppositories work because you have an area that is already rather moist, has excellent blood supply and, in the case of the anus, is *specifically designed *to reabsorb water.

Drugs in suppository format are absorbed very quickly and are typically in the bloodstream far quicker than if you drank the same drug with an empty stomach. In some conditions like, Status epilepticus (a form of epilepsy), a suppository is the de facto treatment because needles and pills aren’t options during seizures.

Drip, drip, drip…

Of course, in hospitals, where most patients already have a drip, then intravenous drugs make sense.

Intravenous drugs, however, require high solubility. For some drugs this is tricky, but chemists are pretty good with playing with molecules to add water-loving parts to improve solubility. The big advantage to intravenous drugs besides the speed of delivery is that it skips the gut.

With a direct line to the blood, lower dosages of drugs can be used. Drugs that would otherwise, struggle to be absorbed by the body, or drugs that can’t withstand stomach acid, can now be used. Most of all, more potent and toxic drugs can be used.

Injection needle

The gut is lined with cells that are constantly dividing and being replaced. And that’s just the part that belongs to you! Increasingly, research into the microbiome, is showing us that the bacteria that live in, and on you, are in a delicate balance and essential to keeping you alive. Strong antibiotics and chemotherapy specifically kill these sorts of cells. Antibiotics wreak havoc with your gut bacteria. Chemotherapy pretty effective kills it off.

No easy answer

As medicine advances, we understand more of the systems that build up our body. The answers are never simple. There is no straight “A” goes to “B” pathways, where this thing goes in, then this thing comes out. No, our bodies on a molecular level are complex webs of interconnected parts. Everything is intertwined and all feeds back to one another.

For example, there is one protein in human cells called mTOR. It acts like a giant control switch, when it is on it tells the cell to grow and divide, when it is off it turns the cell into a hibernating, housekeeping mode.

Traffic light

It sounds exactly like the sort of thing chemotherapy should target to stop cancerous tumours growing. And it is. For some cancers mTOR inhibitors are exactly what the doctor orders. In other cancers, however, recent studies are now showing us that inhibiting mTOR ends up increasing the signal the tells cells to stay alive. The exact opposite of what you want the cancer to be doing.

In the military, leaders have long understood that when brute force fails, try deception. The 11th century Hashashins (from where we get the word assassin) worked out that in the face of overwhelming odds, you don’t need to fight the whole army if you can cut off the head.

Cancer researchers are taking this lesson to heart. Sometimes an indiscriminate, overwhelming attack on a tumour with chemotherapy can be effective, but it risks lot of collateral damage. A more intelligent strategy is required.

Cocktail time!

What is becoming increasingly clear, is that complex problems require complex solutions. One drug, in isolation, is simply not enough. The better solution is to use a cocktail of complimentary drugs. Each drug less dangerous individually, but when used in combination gives tremendous results.

Using an array of drugs in combination means that the cancer can be targeted more effectively. In turn, that means less needs be used. That means, less toxicity, fewer side effects, and crucially, better results.

Cocktail glasses on a bar

Cocktailing is also tricky. Anyone that has ever gone to a cocktail bar, knows that in the hands of a skilled barman, cocktails can be delicious. You can take that same recipe home and practically poison yourself. As with cooking, the best results are obtained with the knowledge of knowing when and how to add the next ingredient. The same is true in fighting disease. If you’re fighting cancer, you first want to slow down and weaken the tumour before you strike with your knockout punch.

One of the best new ideas in drug delivery are nanoparticles, especially in fighting cancer. Measuring billionths of a metre across, they consist of a stable, tiny core to which the chemotherapy can be loaded and often later released.

Various tricks are then used to specifically target the cancer. Most nanoparticles are coated in fatty molecules which make them an appealing energy source to an ever-hungry cancer. Some nanoparticles *sense *the conditions of a cancerous environment. Some nanoparticles can even be linked to antibodies that selectively bind to receptors on the cancer cells. This effectively delivers the bomb right to the cancer’s front door.

Killing cancer with light?

My good friend, Girgis Obaid (now at Massachusetts General, part of Harvard Med) has spent his research career working with light-activated nanoparticles. Working to create a photodynamic cancer therapy. The idea is that a patient can be injected with a large dose of the nanoparticle chemotherapy treatment. After a few minutes, with keyhole surgery, a surgeon can shine a laser on the tumour and turn the harmless nanoparticles into a cancer killer. Crucially, only at the site where the laser shines.

A key advantage to nanoparticles, is their fatty nature. When used with a nebuliser, a device that turns liquids into a fine mist, the nanoparticles can be deposited directly onto the surface into the lungs. Meaning that drugs that are typically hydrophobic (hate water) can enter the body in a controlled manner. In cases like lung cancer, the direct access also greatly improves treatment efficiency.


Nanoparticles are the new drug delivery

Nanoparticles also have amazing cocktail potential. One particularly brilliant use case comes from the Journal of Materials Chemistry where researchers make pacitaxel / curcumin nanoparticles. Curcumin is a derivative of the Indian spice, turmeric and prevents cancer cells from multiplying. It also enhances the cancer’s susceptibility to pacitaxel. Pacitaxel is a potent cancer-killing drug. Both pacitaxel and curcumin are poorly soluble in water, have low efficiency and pretty bad side effects, making them pretty poor chemotherapy options by themselves.

To use pacitaxel and curcumin in combination, effectively, requires expert timing. Deploying the drugs too early means that the cancer has time to defend itself from attack. Wait too long, and the fatty casing of the nanoparticle is too tempting and the cancer cell has already started digestion of it.

The nanoparticles here have two layers. On the surface is the curcumin to stop the cancer cells growing. It is released from the nanoparticle when conditions get more acidic - a classic hallmark of cancer cells. The acidic conditions also slowly dissolve the surface of the nanoparticles releasing the pacitaxel trapped inside. This releases the pacitaxel exactly when the cancer cells are at their weakest and only at the target. Illustration of a nanoparticle

The old one-two

This one-two delivery of drugs, directly to the cancer. Lining them up, before knocking them down, promises to be a very effective treatment. The ultimate goal here is to deliver an unstoppable strike, killing all of the cancer in one blow. No remissions. No prolonged treatments. Targeted therapies with little to no side effects. This of course, will require very specific characterization of the cancer to know its weaknesses before any strike. But, here too, great strides are being made in personalized medicine.

The hypospray injector of Star Trek that doesn’t break the skin for any drug are still largely the work of fiction. (Even though jet injectors that use high-pressure liquid to pierce the skin instead of a needle do exist.)

Next time you have a headache and you reach for the some pills, take a moment to think. Are you taking pills because it is the best way to resolve your headache? Or are you taking pills because society tells you pills = good? In a few years, will you even be taking pills?

This article has previously appeared on previous versions of morganbye.com1 2 and LinkedIn3

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