Researchers Develop Painless 3D Printed Microneedles that Dissolve and Deliver Drugs Under Human Skin

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I hate getting shots more than almost anything, except maybe going to the dentist. Really, it’s seeing the needle puncture my skin that bothers me more than anything – I can’t even look at people getting shots on TV, it totally freaks me out. I need to be distracted, and always warn the nurse or technician about to administer the shot or draw blood that I will talk to them nonstop about anything and everything until it’s over. I assume this is annoying, but thankfully, no one ever seems to mind too much…let’s be honest, they’re probably just glad I’m not going to pass out.

The other unfortunate thing about shots is that they hurt. In 2015, researchers from the University of Akron and the University of Texas Austin were developing a pain-free injection method that involved a biodegradable 3D printed microneedle which could be inserted internally into the body to diffuse drugs. Now, a research team from the University of Texas at Dallas is working on a similar drug delivery project.

The major difference between the two research projects is the 3D printing method – the 2015 research used microstereolithography, while this team is using an extrusion-based process.

Schematic illustration

The UT Dallas team’s 3D printed microneedles are also biodegradable, and will break off underneath the skin and dissolve over time to release the drugs…a far cry from today’s conventional syringes. They are painless, because the microneedle is so thin that patients can’t even feel it when it breaks off.

Traditional syringes may soon be a distant memory. [Image: Retales Botijero, Getty Images]

Syringes and hypodermic needles – which haunt my nightmares – are still the standard method of giving injections, though they can cause bruises if they’re not handled properly. Not only are they painful, but they also leave behind biohazardous waste. The 3D printed microneedles from UT Dallas solve all of these problems.

The researchers published a paper on their work, titled “Biodegradable 3D Printed Polymer Microneedles for Transdermal Drug Delivery,” in ChemRxiv. The co-authors include Michael A. Luzuriaga, Danielle R. Berry, John C. Reagan, Ronald A. Smaldone, and Jeremiah J. Gassensmith; all are from UT Dallas, with either the Department of Biomedical Engineering or the Department of Chemistry and Biochemistry.

The abstract reads, “Biodegradable polymer microneedle (MN) arrays are an emerging class of transdermal drug delivery devices that promise a painless and sanitary alternative to syringes; however, prototyping bespoke needle architectures is expensive and requires production of new master templates. Here, we present a new microfabrication technique for MNs using fused deposition modeling (FDM) 3D printing using polylactic acid, an FDA approved, renewable, biodegradable, thermoplastic material. We show how this natural degradability can be exploited to overcome a key challenge of FDM 3D printing, in particular the low resolution of these printers. We improved the feature size of the printed parts significantly by developing a post fabrication chemical etching protocol, which allowed us to access tip sizes as small as 1 μm. With 3D modeling software, various MN shapes were designed and printed rapidly with custom needle density, length, and shape. Scanning electron microscopy confirmed that our method resulted in needle tip sizes in the range of 1 – 55 µm, which could successfully penetrate and break off into porcine skin. We have also shown that these MNs have comparable mechanical strengths to currently fabricated MNs and we further demonstrated how the swellability of PLA can be exploited to load small molecule drugs and how its degradability in skin can release those small molecules over time.”

Images of unetched FDM fabricated MN arrays at densities of a) 4 x 4, b) 5 x 5, and c) 6 x 6.

The microneedles were designed using Blender software, and 3D printed on a LulzBot TAZ 5 3D printer using biodegradable and, most importantly, FDA-approved PLA filament. The needles are chemically etched post-3D printing to give them that tapered shape.

The UT Dallas researchers were able to 3D print microneedles with different shapes as well, at widths between 400-600 micrometers, and tips as small as a single micrometer; just for comparison’s sake, a human red blood cell measures about 5 micrometers wide. PLA will dissolve in water at mildly acidic or alkaline pH, which is why the microneedles can dissolve once they’ve broken off – human skin is slightly acidic.

SEM images of unetched FDM fabricated MNs.

The system won’t work for all types of medications, but ultra thin microneedles can be used to deliver many drugs if they are made of small molecules, which, according to Xconomy, account for roughly 90% of today’s therapeutics.

Microneedles have a better shelf-life than drugs which are stored as injectable liquids, and offer less risk of infection than typical transdermal injections. Additionally, they give unskilled workers a more safe way to deliver drugs. However, while it’s fairly cheap to 3D print the microneedles, you must obviously have access to more expensive 3D printing equipment in order to do so.

a) Before and b) after images of MN array base plate test with 4 layers.

But the researchers are encouraged by their early results, having successfully tested the 3D printed microneedles on both parafilm and pig skin to see if they would indeed puncture and break off below the skin to deliver drugs like they’re supposed to. The team even determined that 84% of the tested microneedles would break off when they applied sideways force.

There has been a lot of 3D printing research regarding alternative ways to deliver drugs over the last few years. While I’m all for combining multiple vaccines into a single shot, I think we’d all be much happier if that shot didn’t hurt, either.

Discuss this and other 3D printing topics at 3DPrintBoard.com or share your thoughts below. 

[Sources: FuturismCosmos Magazine] / Images: UT Dallas]

 

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