Olivia Merkel - Professor and Chair of Drug Delivery at LMU Munich
Olivia Merkel - Professor and Chair of Drug Delivery at LMU Munich
Biography
First and foremost, I am a scientist who seeks to advance drug delivery systems, particularly for nanomedicine and RNA therapeutics. I have been a Professor of Drug Delivery at LMU Munich since 2015, Chair since 2022, and Co-Director of the Department of Pharmacy since 2024. As a Registered Pharmacist, I earned an additional MS in 2006 and a PhD in Pharmaceutical Technology in 2009. My work has been heavily funded by the ERC through a Starting Grant (2014), Proof-of-Concept Grant (2021), and Consolidator Grant (2022), but also by federal German and foundation funds. I serve as the co-spokesperson for the BMBF Future Cluster CNAT-M and have authored over 140 articles and book chapters. My expertise has led me to serve as an NIH reviewer (2014-2015) and SNF reviewer (2018-2022). Additionally, I am an Editorial Board member for JCR, EJPB, Molecular Pharmaceutics, and other journals, as well as an Associate Editor for DDTR and WIREs Nanomedicine and Nanobiotechnology. I was President of the German Controlled Release Society in 2020 and Chair of the CRS Focus Group on Transdermal and Mucosal Delivery from 2020 to 2022. Currently, I serve as a scientific advisory board member for Coriolis Pharma, AMW, and Corden Pharma and am a co-founder of RNhale. My research focuses on RNA formulation and pulmonary delivery for the treatment of various lung diseases.
Interview
NanoSphere: Tell us a bit about yourself—your background, journey, and what led you to where you are today.
Olivia: I am a pharmacist by training because I was intrigued by the interdisciplinarity of pharmacy. As a high school student, I didn’t know if I wanted to become a math teacher or a scientist or a medical doctor. Most or all, I didn’t want to break any bad news to patients and therefore decided against medicine. I wanted to be the person who has better options, better treatments and hope for patients. But I also really loved Math, Computer Sciences and Natural Sciences. So, I chose pharmacy and would always do it again. While still a student, I learned how pharmacy and computer science work together very nicely. But I was particularly interested in the genetic code and gene therapy as well. When I was offered a student assistantship in Prof. Thomas Kissel’s lab, I knew that I had found my passion for nucleic acid formulation and delivery. That’s where I returned for my pharmacy pre-registration year, and that’s where I did my PhD and where I stayed for a 2-year postdoc before I moved to Wayne State University in Detroit for an Assistant Professor position. The time at WSU certainly taught me what it means to be fully independent and without a support network. I also learned what “wordsmithing” NIH grants means. I learned how to stretch a budget and how to write 4 grants in parallel at all times. WSU gave me a wonderful opportunity to start an independent group at a very young age and I am thankful for it. I had amazing students in Detroit who went through it all with me, even when I took the position in Munich at LMU. Initially I commuted between Munich and Detroit every two weeks to ramp up the new lab in Munich while ensuring that all students in Detroit would have the necessary support to graduate successfully. It was an exciting time, but I am glad to call Munich home now, where I had lots of support with the transition and the growth of my group over the past 10 years.
NanoSphere: You co-founded RNhale GmbH to advance inhalable RNA therapeutics using lipid nanoparticles (LNPs). What have been some of the key formulation and manufacturing challenges in developing RNA-loaded LNPs as an inhalable dry powder? Additionally, how does RNhale’s technology address important aspects such as particle stability, aerosolization, and effective RNA delivery to the lungs?
Olivia: Spray drying RNA-loaded LNPs is a very exciting but also challenging undertaking. We were very lucky that we had years of experience with spray drying nanoparticles before the pandemic hit. One of the biggest challenges in spray drying nanoparticles is trying to fight thermodynamics, i.e. aggregation of nanoparticles. The other two forces that impact the sprayed goods are temperature and shear force. RNA-loaded nanoparticles don’t like either. But luckily, we had optimized process parameters, excipients, tubing materials and many other factors with polymer nanoparticles from 2012-2020 and had just submitted our first patent application when large pharma companies started shipping mRNA-LNPs around the world in sub-minus degree cold storage. We knew there had to be a better way for storage and transportation, and the rest is history. RNhale is now offering solutions for dry/solid dosage forms we didn’t have at the time.
NanoSphere: In your recent publication, you highlight the importance of pKa in ionizable lipid (IL) design for LNP drug carriers. Have you had the opportunity to apply these insights to LNP-mRNA formulations, and what key learnings have emerged? Additionally, what would you consider the best approach for optimizing LNP-mRNA formulations—from design and CQAs (beyond size, zeta potential, and shape) to ensuring stability in both liquid and lyophilized storage?
Olivia: Our latest Density Function Theory paper reflects my love for math J I feel very privileged that I have a very diverse group of people in my lab, who share my interest in RNA therapeutics, material synthesis, formulation, classical pharmaceutical technology, cell culture, and preclinical work and translation. Luckily, some of them also love math, molecular dynamics simulations and machine learning. The question about the apparent pKa has been raised many times in literature, but we didn’t have great ways of addressing it so far. Within our federally funded “AIRMAIL” consortium, we now had the chance to develop an idea based on surrogates and Density Function Theory, which now helps us in developing new ionizable lipids in the future. Our main goal is to decrease wet lab synthesis and become more sustainable. We want to reach this goal by increasing our computational efforts to decide if a material is worth being synthesized or not. I don’t know if this is the best approach because we may overlook materials and formulations if our predictions are not correct. But combined with machine learning, we have been successful in predicting promising materials and efficient formulations, and we therefore heavily rely on it in combination with simulations, experimental screening and validation. Stability, on the other hand is a tricky question. First, we need to separately discuss colloidal stability and encapsulation stability, of course. Colloidal stability is a key concern during drying processes such as lyophilization or spray drying as well as during liquid storage. Encapsulation stability is an ambivalent parameter, on the other hand, where we ideally want great storage stability but also need release (the opposite of stability) at the site of action in the body.
NanoSphere: If there’s one key message or insight you’d like to share with readers for the future of nanomedicine, what would it be?
Olivia: This is an exciting time for nanomedicine where we need to put more effort into clinical translation and less effort into all-singing-all-dancing formulations that may be academically interesting but a regulatory nightmare.
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