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Injectable hydrogels for magnetically-activated, remote-controlled drug delivery

Periodic Reporting for period 2 - INMARE (Injectable hydrogels for magnetically-activated, remote-controlled drug delivery)

Reporting period: 2021-01-22 to 2022-01-21

The problem being addressed is that the delivery of drugs is not controlled in current drug delivery systems, creating non-desired spikes in vaccines or drugs dosing. This is important for society because if we would be able to understand the physics behind the diffusion in the delivery of drugs, and thus improve the delivery of vaccines or drugs by sustaining the dosing, vaccinations and medical treatment of patients will be more effective. The overall objectives of this project are to understand the physics behind drug diffusion and to create biomaterials for sustained drug delivery.

Regarding the conclusions of the action, the key goals of the INMARE project were successfully achieved:

a) A strong a through training of myself in the science, technology and industrial applications of magnetic nanomaterials and drug delivery systems at Stanford University and the host group at University of the Basque Country.

b) I designed, fabricated and developed advanced drug delivery systems. In addition to that, I contributed substantially to the understanding of the Physics behind diffusion in these type of drug delivery systems, by formulating the most accurate predictive model for solute diffusion in hydrogels to date.
Overview of the exploitation

The work performed from the beginning of the project and the main results achieved, together with the dissemination of the results are listed here:

1) Understanding of the physics behind mass diffusion in biomaterials.


A Multiscale Model for Solute Diffusion in Hydrogels

Eneko Axpe, Doreen Chan, Giovanni S. Offeddu, Yin Chang, David Merida, Hector Lopez Hernandez, and Eric A. Appel

Macromolecules, 2019

Eneko Axpe. A multiscale model for solute diffusion in hydrogels. Materials Research Society – Fall

Meeting and Exhibit, 2019, Boston, USA (Oral presentation)

2) Understanding of the physics behind diffusion and mechanical properties in biomaterials for drug delivery in brain.


Towards brain-tissue-like biomaterials

Eneko Axpe, Gorka Orive, Kristian Franze & Eric A. Appel

Nature Communications, 2020

3) Developed an injectable hydrogel for sustained delivery of vaccines.

Injectable hydrogels for sustained codelivery of subunit vaccines enhance humoral immunity

Gillie A Roth, Emily C Gale, Marcela Alcántara-Hernández, Wei Luo, Eneko Axpe, Rohit Verma, Qian Yin, Anthony C Yu, Hector Lopez Hernandez, Caitlin L Maikawa, Anton AA Smith, Mark M Davis, Bali Pulendran, Juliana Idoyaga, Eric A Appel

ACS Central Science, 2020

Eneko Axpe. Injectable hydrogels for bone regeneration. NASA Human Research Program Investigators
Workshop, 2019, Galveston, USA (Invited oral presentation)

4) Developed a hydrogel for preventing biofouling on implantable biosensors.


Combinatorial polyacrylamide hydrogels for preventing biofouling on implantable biosensors

Doreen Chan, Jun-Chau Chien, Eneko Axpe, Louis Blankemeier, Samuel W Baker, Sarath Swaminathan, Victoria A Piunova, Dmitry Yu Zubarev, Caitlin L Maikawa, Abigail K Grosskopf, Joseph L Mann, H Tom Soh, Eric A Appel
Together with my team, I have developed the most accurate predictive mathematical model to predict the diffusion in hydrogels, widely used biomaterials for drug delivery systems. My predictive mathematical model for mass diffusion in hydrogels has been described by other authors such as Prof. Nicholas Peppas (biomaterials eminence and the most cited hydrogel scientist in History) as "a milestone in the development of mesh size theory". The socio-economic impact of this model is expected to save millions of euros by avoiding trial-and-error strategies in developing new drug delivery systems around the world.

I also created, together with my team, a drug delivery system that offers sustained vaccine delivery. This biomaterial, if widely used in the future, could improve the efficacy of vaccines in millions of people by preventing from spikes in dosing and giving the patient a controlled vaccine delivery that it has been proven to increase humoral immunity in animal models.

I have also developed, together with my team, a biomaterial that could be use as a coating material to prevent fouling in implanted medical devices. This could have a huge impact in making the lifespan of implanted biomedical devices longer in millions of patients.
Understanding the mass diffusion in hydrogels to improve drug delivery systems