Drug delivery – now that’s a tricky field. The variety of drug substances is large, and the ways that they’re taken up and distributed in living systems are many. And we’d like control over the process, which we don’t often have. A typical kid’s question is “How does the aspirin know where the headache is?” and the pharmacokinetic answer is “Hah! It doesn’t! That’s why we soak every part of your body in it that the bloodstream can reach!”
And that’s still the norm – get it into the bloodstream and hope for the best, which is sometimes a big enough problem all by itself. You can get slightly more refined by choosing diseases that occur in places where compounds are distributed unusually, although I wouldn’t necessary use “refined” to describe injecting something right into the eye (for example). This is also the thinking of the “Well, we know that this is never going to make it past the liver, so let’s see if we can find something for it to do in the liver” school of thought.
This editorial (from Jean-Cristoph Leroux at the ETH in Zürich) looks at the drug delivery field and asks if perhaps some things are going wrong:
Today, drug delivery is experiencing a major expansion. Recent progress in the field of molecular biology, biotechnology, and material sciences has resulted in the emergence of interesting technologies, which may hold great potential for the development of more efficient and safer pharmacological therapies. Paradoxically, the concomitant upsurge in published reports on drug-delivery systems does not correlate with therapeutic advances.
I know what he means. For some years now, the journals have prominently featured all sorts of highly engineered drug delivery systems – tissue-directed nanospheres and that sort of thing. The work is conceptually quite interesting and seems to hold a lot of potential, but you know, it has been some years now since this stuff started to appear, and the number of these things that have made a dent in the real world is small. Admittedly, there’s a pretty severe time delay involved, with regulatory concerns a big part of it. But the editorial is worried that there’s been too much of a trend towards exotic, overengineered formulations and delivery platforms that will have trouble making it through such hurdles in the first place.
Some of the assumptions behind these efforts may not hold up, either:
Indeed, a large proportion of what is nowadays published, especially in chemistry and nonspecialized journals, relates to nanosized carriers (nanoparticles, nanocapsules, drug–polymer conjugates, etc.) aimed at directing anticancer drugs to neo- plastic tissues. In such systems, the tumor-targeting principle generally relies on the enhanced permeation and retention (EPR) effect. However, this constitutes the main limitation of the “nanomedicine” dogma, since the EPR effect is increasingly recognized to be much less prominent in humans than in the classical rodent models employed to demonstrate antitumoral activity.
One might ask whether some of these things are “funding bait”, going after high-profile subjects like cancer with high-profile approaches like nanotechnology. It would be unfair to characterize the whole field like this, but it would be unrealistic to pretend that this isn’t a factor, either. And by “funding”, I have in mind both academic grants and industrial biopharma money as well.
They’re certainly “publication bait” in many cases, and that’s one of LeRoux’s big points: the specialist journals in this area are publishing a bit less of the gaudy stuff, which is instead showing up in the broader-interest journals. And that stuff is perhaps not getting the detailed reviewing it should when it moves up in this fashion, which is a general problem in the literature. You end up with a situation where the highest-profile publications end up as some of the less potentially reproducible ones, a situation that the chemists and biologists in the crowd will be familiar with. Toxicity is just one of the issues that can get swept under the scientific rug under these conditions.
Reproducibility is another thing that LeRoux highlights, and he makes the (valid) point that in a field as close to the clinic as drug formulation and delivery that it really should have higher standards than usual. These are technologies that could have direct impact on human patients and volunteers, and some serious money will be spent in that regard. The field is not well served by the excuse that finicky details are hard to translate from one lab to another – this is an area, like process chemistry, that is supposed to be hammering those sorts of things out, not using them to rationalize trouble. The whole point is generating robust work.