Cutting-edge technology synergy in the personalised nanomedicine space: Focus on 3D printing nanomedicines

Cecilia Van Cauwenberghe from Frost & Sullivan’s TechVision synergy Group explains the role of cutting-edge technology in the personalised nanomedicine space, with a special focus on 3D printing nanomedicines

When it comes to understanding cutting-edge technology synergy, let’s start by looking at
how 3D printing is meeting nanotechnology. Two-photon polymerization (TPP) based 3D printing technology revolutionised many industries by allowing printing objects at nanoscale resolution. By using a near-infrared femtosecond laser, TPP-based 3D printing
technique solidifies photoresist for the assembly of ultra-precise 3D nanostructures. In fact, it is the laser power that determines the final resolution, along with the exposure time and the efficiency of TPP initiators.

According to a very recent publication (Zhu et al., 2018), the principal challenge to a broader spectrum of biomedicine applications of this technology is associated with the ease of aggregation and precipitation of nanomaterials when they are used in printable inks, hence demanding complex stabilisation procedures. Most active pharmaceutical ingredients (APIs), especially new chemical entities (NCEs), exhibit poor solubility. Therefore, overcoming solubility issues by using new technologies such as nanotechnology appears promising. How is 3D printing empowering nanomedicine?

Inkjet printing and drug nanonization procedures have been successfully combined at the research level (Cheow et al., 2015). Similarly, various nanosuspensions have been utilised as inks in two well-renowned research studies (Palo et al., 2015; Pardeike et al.,
2011). However, a more recent review (Preis and Rosenholm, 2017) comments that although in all these cases, the active agents have been formulated as a nanosuspension, even more advantages could arise by incorporating the agent into a nanocarrier, further formulated into an ink for 3D printing of high precision, personalised therapeutics. According to the authors, the utilisation of nanostructures as drug carriers, along with the simultaneous incorporation of a stabiliser in the ink, can facilitate printability.

Printers designed for bioprinting are usually pressure regulated, instead of thermally or piezo-electrically regulated to avoid damage on thermo-labile ingredients. Nevertheless, more sensitive substances, such as biomolecules, can be affected, even by shear forces. Therefore, the incorporation of these molecules into a nanocarrier can significantly enhance bioavailability and stability during print processing (Giner-Casares et al., 2016).

How is 3D printing supporting regenerative medicine?

3D printing technology is paving the way for personalised medicine by enabling individual configuration (Shafiee and Atala, 2016). 3D printing technology is being widely used to create biofunctional scaffolds, in which nanocarriers are introduced for monitoring and control of stem cell behaviour after transplantation (Rosenholm et al., 2016). Moreover, the same approach can be used to design personalised drugeluting implants through the creation of a biomimetic bone-specific environment (Van Cauwenberghe, 2015). Therefore, 3D printing technology can be used to mimic different biological microenvironments that may potentially function as powerful tools for studying cancer metastasis and assessing drug response sensitivity, among many other applications. Interestingly, fluorescent
nanoparticle inks can be used as biomarkers or labels to enhance biomedical imaging techniques. 3D printing has allowed the generation of a broad spectrum of customised implants, principally spinal and craniofacial implants, as well as, cardiovascular stents.

Similarly, this technology has also facilitated the generation of multiple cell types via 3D bioprinting by originating a variety of cell patterns in a restrained space, while preserving cell function and viability within the printed construct.

Final remarks

The future landscape for 3D printed nanomedicines is a revealing perspective. The development of highly sophisticated drug delivery platforms and realistic diagnostic
systems that enable the delivery of precise and personalised medicine solutions is certainly being energised by the introduction of 3D printing technologies.

Printable nanomedicines are expected to have a major impact on the nanomedicine market over the coming two to three years. The regenerative medicine space has been substantially energised with the advent of stem cells. 3D printing platforms constitute promising tools due to their ability to conform structures and devices with atomic- scale precision and accuracy. Fundamental building blocks are able to fold, join, build and grow by themselves, perfectly well-matched to building nanostructures.

Binding can be specifically tailored so that customised parts can be combined to bind with each other and construct exotic structures. Novel techniques focus on printing a grid-like 3D structure laden with stem cells to enhance the discovery of personalised nanomedicines is something that has gained an increased amount of attention.

Acknowledgements

I would like to thank all contributors from industry involved with the development and delivery of this article from the TechVision Group at Frost & Sullivan.

References

1 Cheow, W.S., Kiew, T.Y. and Hadinoto, K., 2015. Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs. European Journal of Pharmaceutics and Biopharmaceutics, 96, pp.314-321.
2 Giner-Casares, J.J., Henriksen-Lacey, M., Coronado-Puchau, M. and Liz-Marzan, L.M., 2016. Inorganic nanoparticles for biomedicine: where materials scientists meet medical research. Materials Today, 19(1), pp.19-28.
3 Palo, M., Kolakovic, R., Laaksonen, T., Määttänen, A., Genina, N., Salonen, J., Peltonen, J. and Sandler, N., 2015. Fabrication of drug-loaded edible carrier substrates from nanosuspensions by flexographic printing. International journal of pharmaceutics, 494(2), pp.603-610.
4 Pardeike, J., Strohmeier, D.M., Schrödl, N., Voura, C., Gruber, M., Khinast, J.G. and Zimmer, A., 2011. Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble drugs in personalized medicines. International journal of pharmaceutics, 420(1), pp.93-100.
5 Preis, M. and Rosenholm, J.M., 2017. Printable nanomedicines: the future of customized drug delivery?
6 Rosenholm, J.M., Zhang, J., Linden, M. and Sahlgren, C., 2016. Mesoporous silica nanoparticles in tissue engineering–a perspective. Nanomedicine, 11(4), pp.391-402.
7 Shafiee, A. and Atala, A., 2016. Printing technologies for medical applications. Trends Mol. Med. 22 (3), 254–265.
8 Zhu, W., Webster, T.J. and Zhang, L.G., 2018. How can 3D printing be a powerful tool in nanomedicine?
9 Van Cauwenberghe, C., 2015. Trends in Nanomedicine – Nano-based science paving the precision medicine era. Frost & Sullivan TechVision Analysis. D6C0.

Cecilia Van Cauwenberghe, PhD, MSc, BA
Associate fellow and senior industry analyst
TechVision Group, Frost & Sullivan
cecilia.vancauwenberghe@frost.com
ww2.frost.com
www.twitter.com/Frost_Sullivan