Anne des Rieux (Université Catholique de Louvain, Belgium): Enhancing Drug Delivery to the Central Nervous System Using Advanced Materials

Anne des Rieux is an Associate Professor at the Université Catholique de Louvain (UCLouvain, Belgium) and is part of the Advanced Drug Delivery and Biomaterials unit (Louvain Drug Research Institute). She obtained her PhD degree in Pharmaceutical Sciences from the UCLouvain in 2006 on oral drug delivery. Then, she spent 1 year as a postdoc as a BAEF fellow at the Northwestern University in Chicago (2007) in the Shea Lab where she worked on drug delivery strategies for spinal cord repair. She became a principal investigator (FNRS Research Associate) in 2011 and a full Professor at UCLouvain in 2022. She focuses her research on drug and stem cell delivery for the central nervous system repair.

Enhancing Drug Delivery to the Central Nervous System Using Advanced Materials
Anne des Rieux
UCLouvain, LDRI ADDB, Brussels, Belgium

Amongst acquired demyelinating diseases, the most well-known is multiple sclerosis (MS) affecting approximately 2.5 million people worldwide, with a 3:1 Women:Men ratio. Most forms of MS arise from an autoimmune disorder and progress in a relapsing, remitting fashion1. Despite the severe lack of effective therapies for demyelinating diseases2, promising molecules/therapeutic approaches are emerging but their translation to the clinic is limited yet.

Indeed, delivering drugs to the central nervous system (CNS) remains a formidable challenge, with fewer than 2% of newly developed drugs successfully reaching the CNS. Recently, our research centers on the development of innovative nanomedicines designed to modulate the CNS microenvironment. Our goal has been to enhance endogenous CNS repair3-6 by delivering molecules known to stimulate remyelination, even though their therapeutic potential was hindered by issues such as low solubility, poor stability, and off-target effects.

One of our most promising breakthroughs was achieved through a single injection of retinoic acid-loaded lipid nanocapsules (LNC) into a localized white matter brain lesion. This treatment was effective in restoring the oligodendrocyte population, a critical step in myelin repair3. Encouraged by these findings, we expanded our approach by (i) combining drugs that offered potentially additive or synergistic effects and (ii) transitioning towards a less invasive administration route, known as the Nose-to-Brain (N2B) pathway.

Through this approach, we successfully enhanced the differentiation of oligodendrocyte progenitor cells (OPC) in vitro by utilizing a combination of retinoic acid and calcitriol-lipid nanocapsules (LNC)7. Furthermore, our research demonstrated that N2B co-administration of retinoic acid and calcitriol-LNC (CARA) significantly increased the number of mature oligodendrocytes in mice subjected to cuprizone treatment.

While promoting OPC differentiation is a crucial step in CNS repair for MS, addressing neuroinflammation is equally vital. With Professor Muccioli (UClouvain), a bioactive lipids expert, we delivered PGD2G-loaded LNC, a potent anti-inflammatory bioactive lipid8,9, via N2B in an Experimental Autoimmune Encephalomyelitis (EAE) model, widely used for MS research10. This approach significantly reduced CNS inflammation marker gene expression11. Our next step involved studying its combination with calcitriol, supporting its potential as an additional treatment for demyelinating diseases.

We have thus demonstrated the benefits of co-encapsulating potent drugs and co-delivering through a non-invasive route in the context of MS, using appropriate therapeutic models. This provides the proof-of-concept that our strategy could offer a viable solution for treating MS and that we should pursue our efforts in that sense.


  1. van der Star, B. J. et al. In vitro and in vivo models of multiple sclerosis. CNS Neurol Disord Drug Targets 11, 570-588 (2012).
  2. Thompson, A. J., Baranzini, S. E., Geurts, J., Hemmer, B. & Ciccarelli, O. Multiple sclerosis. Lancet (2018).
  3. Carradori, D. et al. Retinoic acid-loaded NFL-lipid nanocapsules promote oligodendrogenesis in focal white matter lesion. Biomaterials 230, 119653 (2020).
  4. Zamproni, L. N., Mundim, M. V., Porcionatto, M. A. & des Rieux, A. Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment. Int J Pharm 519, 323-331 (2017).
  5. Carradori, D., Eyer, J., Saulnier, P., Preat, V. & des Rieux, A. The therapeutic contribution of nanomedicine to treat neurodegenerative diseases via neural stem cell differentiation. Biomaterials 123, 77-91 (2017).
  6. 6Carradori, D., Saulnier, P., Preat, V., des Rieux, A. & Eyer, J. NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo. J Control Release 238, 253-262 (2016).
  7. Labrak, Y. et al. The combined administration of LNC-encapsulated retinoic acid and calcitriol stimulates oligodendrocyte progenitor cell differentiation in vitro and in vivo after intranasal administration. . (under review).
  8. Alhouayek, M., Buisseret, B., Paquot, A., Guillemot-Legris, O. & Muccioli, G. G. The endogenous bioactive lipid prostaglandin D2-glycerol ester reduces murine colitis via DP1 and PPARgamma receptors. FASEB J, fj201701205R (2018).
  9. Alhouayek, M., Masquelier, J., Cani, P. D., Lambert, D. M. & Muccioli, G. G. Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol ester in the control of macrophage activation and inflammation by ABHD6. Proc Natl Acad Sci U S A 110, 17558-17563 (2013).
  10. Franklin, R. J. M. & ffrench-Constant, C. Regenerating CNS myelin — from mechanisms to experimental medicines. Nature Reviews Neuroscience 18, 753-769 (2017).
  11. Mwema, A. et al. Lipid nanocapsules for the nose-to-brain delivery of the anti-inflammatory bioactive lipid PGD(2)-G. Nanomedicine 48, 102633 (2023).
Elias Fattal (University of Paris, France): Nanomedicine-Based Strategies for the Treatment of Inflammatory Diseases

Elias Fattal is a full professor in Drug Delivery Science at the University of Paris-Saclay and has been president of APGI from 2003 to 2010. He received his Pharmacy Degree (1983) and Ph.D. (1990) from the University of Paris-Sud and followed an internship in Hospital Pharmacy at the University of Lille (1984-1986). After a post-doctoral position at the University of California, San Francisco, in 1990-1991, he became an Associate Professor (1992) and full Professor at the University of Paris-Saclay (2000). He has been the head of the Institut Galien Paris-Saclay (2010-2019). He has made fundamental and applied contributions to the fields of drug delivery using nanotechnologies for targeted or local delivery of drugs and nucleic acids. He has recently focused on lung nanotoxicity and the design of nanoparticle-based delivery systems to deliver anti-inflammatory drugs and nucleic acids. One of his patents led to Calixarene® Cevidra, a cream for treating external actinide contamination. Prof. Fattal has received the Pharmaceutical Sciences World Congress (PSWC) Research Achievement (2007), the Controlled Release Society Fellow Award (2016), was awarded in 2016 by the French Academy of Sciences for his research at the interface of chemistry and biology and in 2018 received the Maurice-Marie Janot Award. He serves on the editorial board of several scientific journals and is a member of the French Academy of Pharmacy, the French Academy of Medicine, and the European Academy of Sciences.

Nanomedicine-based strategies for the treatment of inflammatory diseases
Elias Fattal
University of Paris-Saclay, Institut Galien Paris-Saclay, Orsay, France

Nanomedicines are today strongly considered for drug delivery in inflammatory diseases since they can cross leaky endothelium reaching the inflammatory sites and release their payload therein. Pegylated liposomes were also shown in rheumatoid arthritis (RA) to be taken up by myeloid cells and transported to inflamed joints. We have designed novel pegylated dexamethasone nanoparticles (NPs). They were obtained using dexamethasone palmitate and DSPE-PEG2000 and characterized for their physicochemical and biopharmaceutical properties. We have evaluated their therapeutic efficacy and joint targeting effect in collagen-induced arthritis (CIA) mice model. Three NPs IV injections at 1mg/kg (eq.DXM) significantly improved CIA symptoms compared to saline or free drug. Fluorescent NPs proved their specific accumulation into inflamed joints. More recently, we have attempted to correct the increased expression of miR-155 in rheumatoid arthritis, which could be responsible for impaired monocyte polarization to anti-inflammatory M2-like macrophages. In this study, two pre-clinical models of RA, the CIA and the K/BxN Serum-Transfer-Arthritis (STA), were used to examine the therapeutic potential of antagomiR-155-5p, entrapped within pegylated liposomes with protamine: nucleic acid core, in the resolution of arthritis and re-polarization of monocytes towards anti-inflammatory M2 phenotype. We demonstrated the biodistribution of fluorescently tagged-pegylated liposomes to inflamed joints 1 hour after injection in arthritic mice. IV injection of the liposomes containing antagomiR-155-5p decreased arthritis score and paw swelling. Moreover, the treatment restored bone marrow monocyte defects in anti-inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells.

Sepsis and acute lung injury can be described as an immune disorder caused by an infection characterized by a cytokine storm. We synthesized cationic phosphorus dendrons and dendrimers platform to deliver TNF-α siRNA in mice models of LPS-induced lung injury. The most efficient dendrimers to complex siRNA are from generation 3 and possess pyrrolidinium as terminal protonated amino end-groups. Dendriplexes were able to promote cellular uptake. Moreover, they led to a good inhibition of TNF-α in the lipopolysaccharide (LPS)-activated mouse macrophage cell line RAW264.7. The highest TNF-α silencing effect (80%) was confirmed in vivo in a murine model of acute lung inflammation induced by LPS after nasal delivery of dendriplexes (v/s free siRNA). The same siRNA was also entrapped in lipid NPs, and we monitored in vitro the intracellular trafficking and their anti-inflammatory effect over time using several imaging techniques and cellular assays. Results suggest that while lipid NPs internalization happens almost instantaneously, SiRNA release and inhibitory effect started at around 16h, which is compatible with emergency treatment. In vivo in the LPS-induced lung injury in mice, lipid nanoparticles carrying siRNA were taken up widely by neutrophils at first and later by macrophages, two main actors of the cytokine storm, which in the case of treatment with anti-TNF-α silencing by siRNA was reduced significantly.

These studies demonstrate the high potential of nanomedicines in the delivery of anti-inflammatory drugs and nucleic acid-targeting signaling pathways involved in inflammation.

Szabolcs Fekete (Waters Corp., USA): Current Trends and Challenges in the Analysis of Small and Large Drug Molecules by Liquid Chromatography

Szabolcs Fekete worked in the pharmaceutical industry (Gedeon Richter Plc) at analytical R&D for 10 years, then moved to the University of Geneva in Switzerland and worked as a scientific collaborator for a decade. In April 2021, he joined Waters Corporation and now works as a consulting scientist. He contributed to ~190 peer reviewed journal articles and co-authored 10+ book chapters and co-edited handbooks.
His current interests include separations of new chemical modalities (including oligonucleotides, RNA therapeutics, proteins, antibody drug conjugates and gene therapy products), fundamentals of chromatography, column technology, new method development approaches and modeling.
He is well known for his various collaborations with both academical and industrial partners.
He was the winner of the LCGC Emerging Leader in Chromatography Award in 2020 and the HTC Innovation Award in 2022.
h index: 51, Citations: ~8000

Current trends and challenges in the analysis of small and large drug molecules by liquid chromatography
Szabolcs Fekete, Matthew Lauber, Mandana Fasth, Thomas H. Walter
Waters Corporation, Cell and Gene Therapy Consumables, Geneva, Switzerland

The number and variety of different pharmaceutical products – such as some new small-molecule drugs, monoclonal antibodies, antibody-drug conjugates, and cell and gene therapy products – is growing rapidly. Importantly, these new pharmaceutical candidates are becoming increasingly complex, whether that be an increasingly complex molecular composition or mode of action.   More than ever, the industry needs new analytical methods to characterize, formulate and perform release testing on these new drug products.

Bringing these complex new drugs to market offers the opportunity to address previously intractable diseases, but it also presents a formidable challenge to ensure their safety and efficacy. In some cases, these drugs, like lipid nanoparticle (LNP) mRNA vaccines, are multi-component ensembles (carrier + payload), which means there are a number of critical quality attributes (CQAs) that need to be monitored at each stage of their discovery and development. In other cases, the pharmaceutical candidate, like a GLP-1 agonist, is being designed to have a mode of action that interrupts a complex biological cascade.  On the whole, increasing the throughput and amount of data generated by an analytical method will help bring more efficacious drugs to market more quickly. Among the most broadly applicable approaches, liquid chromatographic separations offer several possibilities. Therefore, this presentation will mainly focus on the current needs and challenges of liquid chromatography as applied to the analysis of complex therapeutics, including different elution modes (size exclusion, reversed phase, ion exchange and hydrophilic interaction).

New ideas and developments will be discussed (such as „effective column length”, inert column hardware, stationary phase gradients, software-assisted method optimization…). New pharmaceutical applications, and some myths and misunderstood phenomena from the world of chromatography will also be shown and explained.

György M. Keserű (HUN-REN Research Centre for Natural Sciences, Hungary): Designing Bitopic Ligands Against G-Protein Coupled Receptors

György M. Keserű obtained his Ph.D. at Budapest, Hungary and joined Sanofi heading a chemistry research lab. He moved to Gedeon Richter in 1999 as the Head of Computer-aided Drug Discovery. He earned D.Sc. from the Hungarian Academy of Science in 2003 and he was invited for a research professorship at the Budapest University of Technology and Economics. Since 2007 he was appointed as the Head of Discovery Chemistry at Gedeon Richter. He contributed to the discovery of the antipsychotic Vraylar® (cariprazine) that has been approved and marketed from 2016 in US and EU. He served as a director general of the Research Centre for Natural Sciences (RCNS) at the Hungarian Academy of Sciences. From 2015 he is heading the Medicinal Chemistry Research Group at RCNS. More recently György M. Keserű has been appointed as the Head of the National Drug Discovery and Development Laboratory. His research interests include medicinal chemistry and drug design. He has published over 270 papers and more than 10 books and book chapters. György M. Keserű was awarded by the prestigious Overton and Meyer Award of the European Federation of Medicinal Chemistry. He has been elected as Fellow of the Royal Society of Chemistry, as Corresponding member of the Hungarian Academy of Sciences and Member of Academia Europaea.

Abstract: Designing Bitopic Ligands Against G-Protein Coupled Receptors
György. M Keserű
HUN-REN Research Centre for Natural Sciences, Drug Innovation Centre, Budapest, Hungary

G-protein coupled receptors (GPCRs) are considered important therapeutic targets due to their pathophysiological significance and pharmacological relevance. Endogenous ligands bind to the orthosteric binding pocket (OBP) embedded in the intrahelical space of the receptor. During the last years, however, it has been turned out that in many receptors there is secondary binding pocket (SBP) located in the extracellular vestibule that is much less conserved. In some cases, it serves as a stable allosteric site harbouring allosteric ligands that modulate the pharmacology of orthosteric binders. In other cases, it is used by bitopic compounds occupying both the OBP and SBP. In these terms, SBP binding moieties might influence the pharmacology of the bitopic ligands. Together with others, our research group showed that SBP binder moieties contribute significantly to the affinity, selectivity, functional activity, functional selectivity and binding kinetics of bitopic compounds. Rational combinations of OBP and SBP binding moieties therefore might open new ways toward GPCR ligands with designed pharmacology.

[1] G. M. Keserű et al. Chem. Commun., 2020,56, 14167-14170
[2] G. M. Keserű et al. Chem. Commun., 2021,57, 10516-10519
[3] G. M. Keserű et al. Bioorg. Chem. 2021, 111, 104832.
[4] G. M. Keserű et al. Front. Pharmacol . 2022, 9, 847788.

Jan Petracek (Institute of Pharmacovigilance, Czech Republic): Pharmacovigilance Transformation - What Will Stay the Same, and What is Changing

Qualified physician and pharmacovigilance expert gained international recognition with over 22 years of practice in pharmacovigilance and drug safety. He is a co-author of many modern international guidelines at EMA, ICH and CIOMS level. As a consultant, he has been instrumental in providing guidance to many of the world’s leading biotech organizations. In addition to serving clients as EU QPPV, auditor, trainer, and advisor, he is also successful thought leader and entrepreneur in pharmacovigilance area. He has been awarded by DIA for Excellence in Service to pharmaceutical community, and as CEO received HM Queen’s Award for International Business. He is giving back to community by volunteering for International Society of Pharmacovigilance, developing Global Pharmacovigilance Professional Certification program.

Pharmacovigilance Transformation – What is changing, and what will stay
Jan Patracek
Institute of Pharmacovigilance, Prague, Czech Republic

The existing global pharmacovigilance (PV) framework is approaching a pivotal junction. Current practices are marred by substantial disharmony, rapidly increasing global and local regulatory requirements, harmful replication of data, and systemic redundancies that drain resources, challenging both the pharmaceutical industry and regulatory bodies. This inefficiency necessitates a critical evaluation of sustainability. Concurrently, Artificial Intelligence (AI) technologies are revolutionizing the PV landscape, swiftly supplanting the traditional roles in translation, data entry, administrative functions, and data analysis. This technological tidal wave is displacing thousands of workers, signaling a profound shift in the sector. This presentation will dissect the evolution within PV, scrutinize the repercussions of AI integration, and deliberate on the ramifications for employment and regulatory practices. We will further deliberate strategic responses for pharmaceutical leaders and policymakers to navigate these transformations in pharmacovigilance effectively. The presentation is intended to forecast potential outcomes and endorse proactive measures that should be considered to harness the potential of AI in pharmacovigilance while mitigating the associated risks.

Hongbo Zhang (Abo Academy, Finland): Smart Materials Driven Medication

Dr. Hongbo Zhang has multidisciplinary background in pharmacy, biology and biomedical engineering. He graduated his PhD in University of Helsinki and then did his Postdoc in Harvard University and establish his research group in 09.2016 in Åbo Akademi University, Finland. Now he is Professor (Tenure) in Pharmaceutical Biomaterials, and he is also the director of Biomaterials and Medical Device research program. His research focus is to develop novel and effective solutions for the challenging biological and clinical problems. In most of the projects, the clinical doctors are involved. The projects start from a clinical problem, and Dr. Zhang will use the functional material toolbox to assemble a therapeutical nanoparticle/microparticle/scaffold or the combination of them. He has published more than 180 papers with google citation of 10000+, H-index of 58. He is also executive editor in chief for Wiley journal Smart Medicine and depute editor of the Science Partner journal, Research.

Smart Materials for Cancer Treatment
Hongbo Zhang, Professor
Åbo Akademi University, Pharmaceutical Sciences Laboratory, Turku, Finland

Nanotechnology has provided revolutionary impacts for the traditional medication. The nanometer size is highly relevant to many biological conditions, for example 50-200 nm particles tend to accumulate in tumor tissue due to the enhanced permeability and retention (EPR) effect. Moreover, the nanoparticles can be endowed with character of smart, responsive, targeted, and multi-functional properties. Nanotechnology has also shown its capability on drug delivery, including the delivery of small molecular drugs, plasmid, nuclear acids, proteins and cells. My group synthesize all kinds of nanomaterials, and we are especially interested in mesoporous silica nanoparticles (MSN), the metal organic framework (MOF), synthetic and nature polymers, and DNA nanoparticles. We also apply microfluidic technology for nanoparticles and microparticles fabrication. Moreover, we use electrospinning to produce nanofiber-based scaffolds. Here we present the examples on how we utilized nanotechnology to delivery small molecular drug and drug combinations, CRISPR/Cas9 plasmids, mRNA etc. We found that those systems have greatly contributed the cancer treatment. We collaborate with clinical doctors, and we hope very much that we will find hints from those projects on the clinical translational potential.


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