Chemical Cocoon: Preserving Drugs in Silk

16 July 2012

Interview with

David Kaplan, Tufts University

Chris -   Antibiotics and vaccines save lives, but to do so, they usually need to be kept cold and this could be a bitter pill to swallow for 3rd world countries that can't afford the necessary refrigeration, despite having the most to gain from these treatments.  But now, that might be about to change, thanks to a breakthrough by Tufts University scientist, David Kaplan.  He's discovered that wrapping vaccines and antibiotic molecules in a layer of silk can keep them in pristine condition for months, even at temperatures above 40 degrees C.

David -   My lab has studied silk for over 20 years, so we've gotten to know the protein very well.  We've learned how to clean it up, how to purify it, and how to use it in medical devices, and medical materials of all kinds.  As a result of that, we've also studied the ability to put things like enzymes into silk and show that they're inherently very stable under those conditions.  That led us to hypothesise if an enzyme, which is a protein as well, is stable in silk, perhaps there's broader utility to entrap and stabilise other molecules like vaccines where there's a real need and a real challenge.

Chris -   When we say silk, it implies a scarf or a tie or something.  Are we really talking the same stuff that you would weave into a silk scarf or a silk tie when you're doing your work?

David -   Yes and no.  We're certainly talking about the same source material.  So the material we start with comes from the textile world and that's a great thing because that means there's a huge supply of the material available which makes the cost relatively low.  The downside is you would never introduce textile silk into the human body.  You'd have severe problems with inflammation and you would have difficulty.  And so, to use the silk, we and others have learned over the years how to get rid of all the proteins on the silk that otherwise would cause inflammation.  When you do that properly, you have a very nice material that's compatible with the human body and in fact, it's been used and FDA approved in a number of medical devices already.

Chris -   So, you don't get reactions with the immune system for example?  It's a foreign protein so you'd think if you put that into the body that the body would recognise that as not part of it and you'd get a reaction.

David -   That's right and yet, the reactions are very, very tepid and so, you don't see any kind of major problems that you'd expect.  In fact, all the studies published around the world from our lab and others always show that of all the approved degradable polymers used in medical materials, silks always tend to be the lowest in terms of any inflammation or immune response.  So, it has to do with the chemistry of the silk.  It's a very hydrophobic molecule.  It has to do with the fact that it degrades in the body very slowly and I think this combination of features helps to give this very low response.

Chris -   So what did you do?  You took some silk that have been prepared in the way you say and then mix them with antibiotic or even viruses to see what the silk will do.

Silk cocoonDavid -   That's correct.  We create solutions of the silk protein in water and once you have that, we can add in essentially  any bioactive molecule that you would like.  In this study we showed that with vaccines and antibiotics.  Then you have to process that solution into a stable material format and it can be in a form of a film, it can be in the form of a fibre, a gel or we make things like micro needles, sort of like a band aid that can administer through the skin.

Chris -   When you do that, what impact does it have on the stability of the agents that you invest in silk in this way?

David -   A remarkable improvement in stability, not just under refrigeration conditions, but even at temperatures as high as 45 degrees centigrade and even over 6 months, they still retain the far majority of the activity of these vaccines which is quite remarkable I think.

Chris -   Compared with had you not had the silk there, the activity would by that time have just gone to zero.

David -   That's correct.  You would've lost all activity.

Chris -   Do you know how it works?

David -   In the paper, we also discuss a little bit on the mechanism and in brief, what we find is there's clearly some interactions between the silk protein itself and the proteins on - in this case - the inactivated virus that we use that appears to essentially pin the protein together and prevent it from denaturing or aggregating, and losing bioactivity.  That's coupled with the low water content in the silk.  And then the last point is that silk is dominated by these very, very small nanoscale hydrophobic domains.  We call these beta sheets.  These are the crystals.  And because they're very, very small, there's lots of interfaces, lots of room for vaccines and other molecules to pin up against these structures and become immobilised and less prone to be inactivated.

Chris -   It sounds like a pretty awful example for me to give to you especially when we're talking about medical things, but I've won enormous amounts of money in bars by betting people I can bend a cigarette so that one end would touch the filter end and the way you do it is by wrapping it in a 5 pound note and having the investiture of the note around the outside of a cigarette means you can make it do unfeasibly bendy things.  Are the particles that you're putting into the silk, are they effectively being stabilised by this enwrapping or this sheathing in the silk, and that just stops them falling apart?

David -   It's two things - one is exactly what you say.  I think it prevents them falling apart or falling into the mis-shapen form so they're no longer active and the other is it prevents them from aggregating too much because there's not a lot in one spot.  So I think that combination helps a lot.

Chris -   How do you get the particles away from the silk again?  So when you actually want to use the antibiotic or you want to metaphorically smoke the cigarette, when you want to administer the vaccine or whatever, do you need to get it away from silk or is that not necessary?

David -   There are many options.  There are three we most commonly talk about:  One is, you can resolubilise the film with the vaccine in it and inject that and silk has been injected before.  It's safe to use.  There need to be more human clinical trials done, but that would be the easiest format and I think that would be very attractive.  If you don't want to do that, you could certainly solubilise and then separate the vaccine from the silk.  And the third, which we happen to like the best, would be when you fabricate the films, you fabricate them in these micro needle formats that I mentioned before and these become essentially a film, like a band aid strip with little pin pricks on one side so you can simply put that on your skin and the vaccine would then get through the skin based on the dissolution of the silk under the skin.  So you never have to separate it from the silk.  You can just use it as is, as an intact device.  And so, that's very attractive because that's something you could ship around the world and then use on demand.

Chris -   Isn't that amazing?  You can put these things viable for months at higher than body temperature just be mixing them with some silk.  That was David Kaplan from Tufts University in the US and he published that work this week in the journal PNAS.

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