PD Dr. Simon Drescher
Phospholipid Research Center Heidelberg, Germany
The Phospholipid Research Center Heidelberg (PRC) organized a half-day workshop entitled “Progress in Pharmaceutical Research & Development on Phospholipids” on October 12, 2021. This online workshop took place during the LIPIDS 2021 Conference. This hybrid meeting was organized by Professor Elena Vodovozova from the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia, and took place in Moscow as well as in the virtual space.
The PRC has a long tradition of organizing workshops and the last two workshops were held in 2019 in Valencia, Spain (during the Controlled Release Society Meeting, CRS) and Sapporo, Japan (during the Liposome Research Days). Workshops are a good way to engage in a lively exchange with scientists on a defined topic, for example the progress in R&D on phospholipids.
After a brief introduction to the intention and goals of the PRC by PD Dr. habil. Simon Drescher (Managing Director, PRC), the workshop started with a seminar by PD Dr. Peter van Hoogevest (PRC) on “The use of phospholipids to make pharmaceutical line extensions”. He described the use of phospholipid excipients to make Pharmaceutical Form (Dosage Form) Line Extensions of existing drugs as part of a Product Life Cycle Management and provided product examples and development candidates, showing the versatility of phospholipids as key excipients in formulations to develop line extension drug products for any administration route by reformulating existing products. The resulting patented products enable the application of a drug substance for another administration route or show an increased efficacy and/or reduced toxicity of the formulated drug substances, or allow a more convenient use, through reduction of dosing frequency, or adapt a product to regulatory requirements for specific patient populations. Parenteral line extensions for lipophilic drugs using non-toxic phospholipid-based solubilizing formulations are clearly an alternative to products with solubilizing synthetic detergents with the risk for allergic and anaphylactic reactions. The seminar once again clearly highlighted the benefits of phospholipids: they are biocompatible, biodegradable, non-toxic, and available at large scale and of pharmaceutical grade. Besides, they are well known to regulatory authorities. The content of this seminar has also been published as an open access paper in: van Hoogevest, P.; Tiemessen, H.; Metselaar, J. M.; Drescher, S.; Fahr, A., The Use of Phospholipids to make Pharmaceutical Form Line Extensions. Eur. J. Lipid Sci. Technol. 2021, 2000297.
The second seminar “Thermodynamical and structural properties of lipids in 2D- and 3D-model systems” was given by Professor Dr. Gerald Brezesinski (Institute of Applied Dermatopharmacy, Halle/Saale, Germany). In his more physicochemically driven talk, he gave an excellent overview about the different techniques that can be used to obtain in-depth information about 2D- and 3D-arrangement of phospholipid molecules in different molecular assemblies, lipid mesophases and phase states, respectively. Peppered with many examples from his own research, Brezesinski spoke about studies on (phospho)lipid monolayers using techniques such as compression isotherms, InfraRed Reflection Absorption Spectroscopy (IRRAS), Brewster Angle Microscopy (BAM), X-ray Reflectivity (XR), Grazing Incidence X-ray Diffraction (GIXD), and Total Reflection X-ray Fluorescence (TRXF). Using these methods, some of which are very elaborate and equipment-intensive, information about the surface activity, adsorptions kinetics, and phase transitions of (phospho)lipids, their structural parameters and organization within monolayers, as well as interactions of lipid monolayers with different ions and peptides/proteins, respectively, can be obtained.
The next seminar was held by Assoc.-Professor Dr. Avi Schroeder (Technion – Israel Institute of Technology, Haifa, Israel) about “The tumor type and patient gender affect nanomedicine efficacy”. He informed on nanoparticles having many potential benefits for treating cancer, including the ability to transport complex molecular cargoes including siRNA and protein, as well as targeting to specific cell populations. He discussed ‘barcoded nanoparticles’ that target sites of cancer where they perform a programmed therapeutic task. Specifically, liposomes that diagnose the tumor and metastasis for their sensitivity to different medications, providing patient-specific drug activity information that can be used to improve the medication choice. His seminar also described how liposomes can be used for degrading the pancreatic stroma to allow subsequent drug penetration into pancreatic adenocarcinoma, and how nanoparticle’ biodistribution and anti-cancer efficacy is impacted by patient’ gender and more specifically, the menstrual cycle of women. Prof. Schroeder concluded that as the result of the evolution of drug delivery systems into synthetic cells, programmed nanoparticles that have an autonomous capacity to synthesize diagnostic and therapeutic proteins inside the body, show much promise for treating cancer and immunotherapy.
Presentation Prof. Dr. Avi Schroeder
The forth seminar about “Zebrafish as an in vivo vertebrate screening model for nanomedicines” was given by Professor Dr. Jörg Huwyler (University of Basel, Switzerland). He introduced in his talk the Zebrafish embryo (ZFE; Danio rerio) that can act as a vertebrate screening tool to study the circulation and tissue distribution of nanoparticles. The major advantage of this model is that these embryos are not considered as autonomous animals until 120 hpf (hour post fertilization), and therefore one does not require ethical permission/approval to conduct experiments. Other advantages are, for example, the fast development of the ZFE (from egg to larvae within only three days), its optical transparency, and the existence of >30’000 different transgenic/wt/mutant fish lines. Huwyler showed that the use ZFEs as a predictive vertebrate screening model is indeed possible and important organ functions, for example kidney, are fully developed at 72 hpf. He could also clearly demonstrate the applicability of the ZEF model for a) the screening and optimization of liposomal formulations, b) the study of circulation, extravasation, and phagocytosis of engineered nanomaterials, and c) the optimization of gene delivery vectors. Huwyler closed his very informative seminar with an outlook showing the implementation of ZFEs in human xenograft tumor models for targeted gene delivery.
Unfortunately, the presentation by Prof. Dr. Jörg Huwyler is not available because some data has not yet been published. To learn more about the Zebrafish and read the relevant publications, please visit the website of the Zebrafish Project at the University of Basel.
The last seminar was given by Assoc.-Professor Dr. Judith Kuntsche (University of Southern Denmark, Odense, Denmark). Her talk was entitled “Liposome characterization by asymmetrical flow field-flow fractionation”. Using this technique, which is abbreviated as 4AF, in combination with Multi-Angle Light Scattering (MALS), the characterization of colloidal drug carriers such as liposomes regarding their size, morphology, homogeneity, and stability in physiological media is possible. After introducing the separation principles of this method, which is comparable to some extent with size exclusion chromatography, she illustrated the applicability of the 4AF/MALS method showing some examples of her own research, e.g., the release of drug-loaded liposomes (Temoporfin, Testosterone, Corticosterone) and the redistribution between these donor liposomes (including the drug) and empty acceptor liposomes or micelles of different composition. These experiments gave very useful insights in the main transport mechanisms and release kinetics. She concluded her presentation with a comparison of the advantages and disadvantages of the 4AF/MALS method.
Another seminar was planned by Professor Dr. Chezy Barenholz (Hebrew University of Jerusalem, Israel), but unfortunately it could not take place. This will be held later. Nevertheless, this workshop was a great success, as evidenced by the lively discussion after each presentation. We will consider holding this workshop in a similar way every two years. Thanks again to all the presenters. Let's hope that we can all meet again in person next year when it's time for the PRC to invite you to the 7th International Symposium on Phospholipids in Pharmaceutical Research.