(6ay) Ionic Liquids to Overcome Obstacles in Nanoparticle Drug Delivery

The physical chemistry of ionic liquids, which consist of a bulky, asymmetric cation and anion that is liquid at room temperature,¹can be exploited to accomplish a broad range of tasks, which historically have included synthesis,^2,3catalysis,⁴electrochemical,⁵and energy applications.⁶In addition, recently ionic liquids have shown great promise as drug delivery agents, increasing cell permeability and navigating epithelial junctions in both the skin and intestines.^7–11A conservative estimate suggests that 10⁸possible ionic liquid combinations can be fabricated,¹²and within this exists a breadth of manipulatable physicochemical properties leading to shifts in lipophilicity, aromaticity, and intra-ionic interactions,¹³which can be tuned to control interactions between ionic liquid moieties and biological materials.^14–16

The use of nanoparticles as drug delivery systems has grown dramatically due to their ability to deliver drugs in a more effective, safe, and specific way compared to traditional therapeutics,^17–19particularly in the context of administering chemotherapy to treat cancer.^20,21However, the vast majority of nanoparticle technologies do not progress clinically as they face a number of currently insurmountable challenges (some of which are enumerated below), which result in <5 % arriving to their intended destination. My research seeks to revolutionize the field of nanoparticle drug delivery as a whole by solving the big-picture challenges that remain by using ionic liquids. Namely, providing non-invasive and localized delivery avenues (Project 1), methods to avoid the formation of a protein corona and subsequent macrophage uptake in the bloodstream (Project 2),²²and improved cellular entry and controlled release once the nanoparticle reaches its destination (Project 3). The technology proposed herein could be applied broadly to many existent nanoparticle delivery systems and thus is of high potential impact.

This proposed work unites my previous research interests in ionic liquids, nanoparticles, and drug delivery. My D.Phil. pioneered the electrochemical quantification of polymer-stabilized nanoparticles suspended in ionic liquids. My current postdoctoral work tackles understanding the efficacious transdermal delivery of drugs and proteins using ionic liquids. I have published these results in 34 peer-reviewed journal papers, 16 as first author, including a first-author publication in Angewandte Chemie. I have two more papers that are currently under review.

Teaching Interests:

With respect to mentorship and teaching, I have thus far formally advised 17 students at the University of Oxford and Harvard University. The educational levels of these students have varied from first-year undergraduates, through to second-year Ph.D. candidates. In all cases, I was actively involved in designing the students’ projects, ensuring they had the skills and information they needed to succeed, and co-authoring original research papers that were published in well-ranked international journals (13 in total). By mentoring a range of different students at different stages of their academic careers, I have extensive practice of keeping projects on track and ensuring that students feel supported, whilst also developing future researchers with the confidence to approach research problems independently. I have previously taught content at a variety of levels in a variety of contexts, including as a Lecturer, Demonstrator, and Tutor in the UK, Australia, and the USA. I have consistently received very positive feedback from my past students and colleagues on my ability to communicate difficult concepts, retain high levels of student engagement, and spark interest in research.

Whether in a laboratory, lecture theatre, or tutorial room, my pedagogical goal is to create an atmosphere that is both academically challenging and inclusive. In my experience, creating a conversation where the students are active participants is crucial in retaining their interest and attention, and enhancing their understanding of the material. As a tutor at St John’s College, Oxford, I did this by primarily working on the whiteboard and asking students to share their working for each question from a problem set with their colleagues. When questions were raised, I guided the discussions, but gave students the opportunity to reason their way to the answer as a group before sharing the solution. My accessibility as an instructor meant that within a few weeks all members of the class felt comfortable engaging with each other and with me.

Retaining typically underrepresented students is another one of my interests as an instructor. In particular, I embrace the opportunity to act as a visible role model for young women in the physical sciences and in engineering, and this is particularly true when I am teaching classes where female students are a minority. I am aware of the existence of my own unconscious biases, and I actively work to combat these and redress systematic inequalities that may prevent students from reaching their full potential as engineers. I am committed to ensuring that students feel a sense of belonging and inclusion in my classes.

Finally, I enjoy sharing with students the scope and impact of chemistry and engineering. In my experience, tying in topics with curated examples from contemporary research excites students, as they begin to see where they might begin to fit in themselves. Whilst teaching Electrochemical Methods at the University of Oxford, I shared examples of electrochemical detection devices involving nanotechnology, including original images from my own research. This stimulated discussion in the lecture and gave the students a feel for the ways in which the theoretical material I was teaching them intersected with current research priorities.