April 23, 2020

Microneedle arrays for vaccination through the skin

3D-printed prototype of an array of microneedles
3D-printed prototype of an array of microneedles. These needles are designed for the efficient delivery of vaccines into specific skin layers. Image: Emrullah Korkmaz, University of Pittsburgh

To fight against a number of diseases, including viral infections, cancer and allergies, there is a strong need to engineer cutaneous drug delivery systems for vaccination through the skin. Scientists from the University of Pittsburgh join efforts to develop a novel device for cutaneous vaccination based on microneedle arrays fabricated by a Nanoscribe 3D printer. They implement additive micromanufacturing to create microneedle array prototypes and use them as master molds in replication processes to upscale the production of dissolving microneedle arrays.

Researchers around the globe are developing vaccines to safely and efficiently prevent the spread of a variety of diseases, such as COVID-19 caused by the SARS-CoV-2 coronavirus. Vaccines can help fight infectious diseases by stimulating our immune system. However, current routine vaccinations use painful hypodermic needle-based injections that deliver antigens into muscle or subcutaneous tissues instead of immunologically rich skin microenvironment. As such, prevailing vaccination strategies result in low immunogenicity and poor patient compliance, leading to a lower rate of global immunization coverage.

3D Microfabrication for cutaneous vaccine delivery systems

To tackle this issue, an interdisciplinary team of scientists and engineers from the University of Pittsburgh’s Department of Dermatology, Department of Bioengineering, Clinical and Translational Science Institute, McGowan Institute for Regenerative Medicine, and the UPMC Hillman Cancer Center develop dissolving microneedle arrays for cutaneous vaccine delivery systems. The researchers use a Nanoscribe Photonic Professional system at the University’s Nanoscale Fabrication and Characterization Facility to print prototypes and masters of microneedle arrays to enable fabrication of dissolving microneedle arrays. These drug delivery systems aim to facilitate diverse immunization strategies.

The researchers tell that when designing microneedle arrays for cutaneous drug or vaccine delivery, Nanoscribe’s 3D printer allows them to think freely without worrying about the design complexities, while also offering great ease of use. Accordingly, they report that Nanoscribe’s systems not only attract engineers, but also impress medical scientists who do not necessarily have microfabrication expertise, and look for simple ways to realize their ideas. For both disciplines, 3D microfabrication has become a key technology to achieve optimization of cutaneous drug or vaccine delivery systems.

To ensure successful skin delivery, their microneedle design includes sharp tips, rounded bases, and undercut features. The tip radii of the microneedles are a key player in tissue insertion forces. Intuitively, the sharper the needles are, the better their skin penetration performance is. Nanoscribe enables the fabrication of sharp microneedles with nanoscale resolution. Further, the fillet at the base of the needles is critical for improving the strength performance of the microneedles during application. Different design parameters can be optimized with microscale additive manufacturing without any complex requirements.

Scalability of microneedle arrays by replication processes

Dissolving microneedle arrays are made of water-soluble biomaterials. These needles are mechanically strong enough in their dry state to penetrate the outermost layer of the skin, known as stratum corneum. Upon insertion into the skin, they then dissolve and release their cargo into the skin microenvironments. To improve the productivity of manufacturing of dissolving microneedle arrays, the researchers have developed a replication-based process to allow serial production.

Replication process chain
Replication process chain from a microneedle array design to a set of vaccine-loaded dissolving microneedle arrays. Source: Emrullah Korkmaz, University of Pittsburgh

The fabrication of microneedle array prototypes by 3D Microfabrication is a pivotal step for reproducible manufacturing of dissolving microneedle arrays. Starting from a CAD design it is possible to fabricate a 3D-printed microneedle array (MNA) in one printing step. Using soft lithography, an elastomer negative mold of the 3D printed master MNA is fabricated. The next processing step uses the negative mold to fabricate replicas out of it by UV micromolding. Several replicas (e.g., 6 in this case) can then be mounted onto a 3D-printed holder fabricated by a PolyJet 3D printing technology. From the resulting microneedle array master mold, the researchers fabricate microneedle array production molds through soft lithography, and then apply a spin-drying technique to manufacture final dissolving MNAs incorporating multicomponent vaccines, as explained in the figure.

Novel drug delivery systems, such as microneedle arrays, can benefit from replication processes to upscale the production of the high-precision parts. These advances will help to move toward the scalability required in industrial manufacturing for widespread application of cutaneous vaccination. 3D Microfabrication is thereby the decisive factor for the precision of the instruments.

Read the scientific publication here: Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination

Login Register
Contact us

It's your choice

Cookies help us to better understand you as a visitor and to provide you with a better experience.

It's your choice
Cookies help us to better understand you as a visitor and to provide you with a better experience.
Legal Notice Privacy Policy
Accept all Individual Settings