International Online Symposium on Phospholipids in Pharmaceutical Research
PD Dr. Simon Drescher
Phospholipid Research Center Heidelberg, Germany
The Phospholipid Research Center Heidelberg (PRC) organized its first “International Online Symposium on Phospholipids in Pharmaceutical Research” on September 14, 2021. Due to the still ongoing pandemic situation and the related travel restrictions, the PRC decided early this year to postpone the face-to-face symposium until September 2022 and to hold an online meeting instead. In retrospect, this was a very good decision.
Founded in 2006 with generous support from Lipoid GmbH and Phospholipid GmbH, the Phospholipid Research Center is dedicated to exploring and exploiting the full potential of phospholipids. The PRC promotes research into new and optimized applications for phospholipids, with a focus on developing new and improved dosage forms for pharmaceutical use. Due to the diversity of applications and properties of this fascinating group of substances, the networking of international scientists with different interests in phospholipids is necessary and one of the essential tasks of the PRC. For this reason, to offer a platform for scientific exchange, this international online meeting took place. The response was overwhelming; we had over 250 registered participants from all over the world covering both academia and industry. Divided into four sessions, the audience was able to listen to interesting presentations by outstanding international experts. But it was not only seasoned scientists who gave presentations, but also young, up-and-coming scientists were given a platform to present their research. And it was precisely this healthy mix of "young and old" that made this event so special.
Morning Session I - Analytics and more ...
The first, analytical session chaired by Prof. Dr. Andreas Koeberle (University of Innsbruck, Austria) started with a plenary lecture about the diversity of lipid modifications in physiology and pathophysiology called epilipidome. Dr. Maria Fedorova (Technical University Dresden, Germany) summarized in her talk the development of several analytical approaches—by combining mass spectrometry (MS) with bioinformatic tools—for the detection, identification, and relative quantification of complex oxidized lipids in biological context specific manner. In the next talk, Dr. Maria Hoernke (University of Freiburg, Germany) described the use of membrane-active, biomimetic polymers that induces membrane perturbations. This is of interest for diverse therapeutic applications such as the mimicking of antimicrobial peptides, or to assist in drug delivery or to enhance endosomal escape. The third presentation in this session was given by Dr. Christian Nehls (Research Center Borstel, Leibniz Lung Center, Germany), which focused on the development and application of microfluidic-derived cell-sized vesicles. Microfluidics might be used in the future to create bacterial envelope models that could be used for compound characterization and screening by vesicle trapping. In the next talk, Dr. Simona Sennato (La Sapienza University Rome, Italy) presented a technique named laser transmission spectroscopy (LTS). The LTS-based approach allows the determination of the colloidal properties of liposomes, i.e. true geometrical size and volume fraction, and the evaluation of the actual drug entrapment capability of the nanocarriers. In the final seminar of this session, Jun.-Prof. Dr. Carla Schmidt (Martin Luther University Halle-Wittenberg, Halle/Saale, Germany) gave interesting insights in the importance of protein/lipid interactions. She presented the available strategies and current developments for identification of lipids in protein assemblies applying different mass spectrometric techniques and further highlighted the application of membrane mimetics for structural MS of protein/lipid complexes.
Morning Session II - Drug Delivery I
The second morning session, which was dedicated to “Drug Delivery” in all its forms, was chaired by Prof. Dr. Gert Fricker (University Heidelberg, Germany). The plenary lecture tried to give an answer to the question whether it is not too challenging to load drugs into extracellular vesicles (EVs). Prof. Dr. Jean-Christophe Leroux (ETH Zurich, Switzerland) explained in a very appealing seminar different methods to achieve this aim, loading low molecular weight compounds into EVs. These EVs have received increasing interest in the field of pharmaceutical sciences in recent years, since they are able to interact and exchange information with cells in a remote fashion. In the second presentation, Dr. Philipp Uhl (Heidelberg University Hospital, Germany) presented a novel, highly potent vancomycin derivative to combat multidrug-resistant bacteria. In his liposomal delivery system, he also applied cell-penetrating peptides (CPPs) to boost oral delivery of the peptide drug and tetraether lipids (TELs) to enhance the stability of the drug vesicles in the gastrointestinal tract. A fascinating approach to making sensitive active pharmaceutical ingredients (APIs) available for oral application. The next seminar on “Light activated liposomes for controlled drug release” was held by Dr. Tatu Lajunen (University Helsinki, Finland). He discussed the use of light-triggered indocyanine green (ICG) liposomes in combination with different surface coating material to carry cargo into the cells and delivering it upon request to the nucleus. This seems to be a promising option for systemic or ocular treatment for several difficult-to-treat diseases. In the forth talk of this session, Dr. Tristan Le clainche (University Grenoble-Alpes, France) showed a very similar approach to overcome chemotherapy resistance in pancreatic cancer. Photosensitizers such as benzoporphyrin derivatives are used to produce reactive oxygen species upon light excitation. By including photosensitizers in liposomes composed of oxidation-susceptible unsaturated phospholipids, he provided compelling proof for the spatiotemporal-controlled release of drugs with light. The last lecture of this session was dedicated to the treatment of Staphylococcus aureus infections. Magda Ferreira, PhD student in the group of Dr. Manuela Gaspar (University of Lisbon, Portugal), showed in her talk that rifabutin can be efficiently encapsulated in liposomes preserving its antibacterial activity against both planktonic and biofilm forms of the reference strain. This presentation once again underlined an outstanding property of liposomes: their ability to specifically target infected areas and interact with biofilms, releasing the incorporated antibiotic at therapeutic levels within the infection site.
Afternoon Session I - Drug Delivery II ... and more
The first afternoon session was chaired by PD Dr. Peter Hoogevest (PRC Heidelberg, Germany) and was also dedicated to “Drug Delivery” but with a greater focus on oral/topical forms of application or other lipid mesophases. The first speaker, Prof. Dr. Martin Brandl (University of Southern Denmark, Odense, Denmark), explained in his plenary lecture the oral use of mono- and diacyl phospholipids to produce solid dispersions of APIs, Celecoxib in this case, to enhance its solubility and permeability. He clearly illustrated that higher drug solubility does not proportionally lead to enhanced permeability and bioavailability, highlighting the importance of evaluating both. He further discussed molecular mechanisms that might explain the effect of phospholipid formulations on the permeability of Celecoxib. The second talk was entitled “Development of effective ligands for liposomal targeted drug delivery in rhabdomyosarcoma”. Dzhangar Dzhumashev, PhD student in the group of Dr. Michele Bernasconi (Bern University Hospital, Switzerland) explained in his talk the surface modification of liposomes using two different peptides leading to an enhanced binding and internalization of these functionalized liposomes to rhabdomyosarcoma cell lines. The third talk was given by Antoine Bernasqué, PhD student in the group of Prof. Dr. Chrystel Faure (CNRS, University Bordeaux, Institute of Chemistry & Biology of Membranes & Nano-objects, Pessac, France). His talk dealt with artificial skin penetration of hydrocortisone encapsulated in phospholipid-based, multi-lamellar liposomes (MLLs) focusing on the influence of the corticosteroid’s encapsulation on MLLs properties, and the fate of the encapsulated API within the artificial skin model. In the fourth presentation, Mehdi Ravandeh (University Greifswald, Germany) discussed the role of sphingomyelin (SM) in eye lens membrane. He showed the audience that SM plays a protective role against oxidative damage in the membrane and that the SM content in lens cell membrane is increased during aging to protect the eye from oxidative damage in the absence of effective antioxidant systems and to prolong lens transparency. The second plenary lecture, and final seminar of this session, was given by Prof. Dr. Katarina Edwards (Ångström Lab, Uppsala University, Sweden). She gave an inspiring talk on polyethylene glycol (PEG)-stabilized lipodisks—from their discovery to their application in targeted drug delivery. She showed that lipodisks, which could be understood as planar, disk-like alternatives to liposomes without an aqueous interior, are remarkably robust and can be used as a versatile platform for the co-delivery of chemotherapeutic drugs and membranolytic anticancer peptides.
Afternoon Session II - LNPs and more ...
The final session of this Online Symposium was chaired by Prof. Dr. Yechezkel (Chezy) Barenholz (Hebrew University of Jerusalem, Israel). In the first plenary lecture of this session, Prof. Dr. Pieter Cullis (University of British Columbia, Vancouver, Canada) gave a very impressive and inspirational presentation about lipid nanoparticles (LNPs) and their role in gene therapies. He described the design features that were followed to develop Onpattro®—a LNP with single-interfering(si) RNA to silence transthyretin in hepatocytes—and how related technology is being employed to construct mRNA-based drugs that are enabling gene therapies generally. A notable example in this context is the development of the Pfizer/BioNTech mRNA vaccine, which is playing a leading role in alleviating the Covid-19 pandemic. In a remarkable lecture, Dominik Witzigmann (NanoVation Therapeutics and NanoMedicines Innovation Network, Vancouver, British Columbia, Canada) explained the role of (phospho)lipids in the design of LNP technology for nucleic acid delivery. With both the ionizable lipid and the PEG lipid optimized for their respective functions, the role of the other two “helper lipids” in common LNP formulations, mainly DSPC and cholesterol, has not been studied in detail. Witzigmann showed results regarding the impact of these “helper lipids” in modulating LNP stability, nucleic acid entrapment, uptake rate, and gene delivery potency. In the next presentation, Eleni Papadopoulos, PhD student in the group of Prof. Dr. Wolfgang Friess (Ludwig Maximilians University Munich, Germany), discussed the use of lyso-phosphatidylcholines (LPC) as an interfacial stabilizer of proteins in liquid parenteral formulations showing its potential at concentrations far below the parenterally toxicity level. This opens a new field of research for (lyso)lecithins and probably provides an alternative to the controversially discussed synthetic surfactants currently used in protein formulations. The session, and the Online Symposium, concluded with another plenary presentation given by Prof. Dr. Raymond Schiffelers (University Medical Center Utrecht, the Netherlands). In his excellent presentation, he compared natural versus synthetic LNPs for the delivery of RNA. As a result, synthetic LNPs remain the method of choice for delivery of nucleic acid therapeutics. Yet, Schiffelers demonstrated that the study of the uptake, internalization, and cytoplasmic release of extracellular vesicles offers opportunities to further enhance lipid nanoparticle delivery efficiency.
The time after each lecture and at the end of the sessions was used for intensive and lively discussions; many questions of the audience could be answered, and it was shown once again that the story of phospholipids is far from being finished. The PRC would like to take this opportunity to thank again for the great participation, the Chairs for their great leadership of the sessions, and of course all the speakers. Many thanks! It was great. Let's hope that we can all meet again face-to-face next year when it's time for the PRC to invite you to the 7th International Symposium on Phospholipids in Pharmaceutical Research.