17th Liposome Research Days

On June 12-15, 2022, the 17th Liposome Research Days will be held at the University of British Columbia, Vancouver, BC, Canada. The Organizer are Terry Allen and Pieter Cullis.

For more information: nanomedicines.ca/LRD-2022/ or visit the conference website.

The Phospholipid Research Center will organize a workshop during this meeting. On Tuesday, 14 June, three of our project partners will give a presentation:

Prof. Dr. Jörg Huwyler - University of Basel, Switzerland

Zebrafish as an in vivo vertebrate screening model for nanomedicines


Zebrafish (Danio rerio) embryos can be used as a vertebrate screening model to assess the circulation in blood and extravasation behavior of nanoparticulate drug delivery systems in vivo. To validate this novel approach, monodisperse preparations of fluorescently labeled liposomes with similar size and zeta potential were injected into transgenic zebrafish lines expressing green fluorescent protein in their vasculature. Phosphatidylcholine-based lipids differed by fatty acid chain length and saturation. Circulation behavior and vascular distribution pattern were evaluated qualitatively and semi-quantitatively using image analysis. The circulation patterns in the zebrafish model did correlate with published and experimental pharmacokinetic data from mice and rats. Our findings indicate that the zebrafish model is a useful vertebrate screening tool for nanoparticulate drug delivery systems to predict their in vivo circulation behavior with respect to systemic circulation time and exposure. We will present examples from ongoing research projects to demonstrate how this model can be used to close the gap between empiric nanoparticle design, in vitro assessment of nanomedicines, and in vivo experiments in rodents.

PD Dr. Michele Bernasconi - University of Bern, Switzerland

Targeted liposomal drug delivery to pediatric sarcomas


Pediatric sarcomas account for about 15% of pediatric cancers, with high relapse rates and extremely poor prognosis. The aggressive chemotherapies needed to fight relapsed tumors have a significant toxicity generating late side effects, a major complication in pediatric oncology. Liposomal formulations can decrease systemic side effects by passive accumulation through the enhanced permeation and retention (EPR) effect. We investigated the possibility to further increase local drug concentration, and to overcome the clinical limitations of the EPR effect, by targeting liposomes to the tumor site. We selected ligands (peptides, nanobodies) with strong affinity for rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. These were used to formulate liposomes (egg sphingomyelin, cholesterol, C16PEG2000-ceramide (PEGC), and either DSPE-PEG2000 (DPEG) or peptide-labeled DPEG) loaded with vincristine (VCR). Initially, in a subcutaneous xenograft mouse model of RMS, we could observe higher accumulation of liposomal VCR in tumors and increased circulation time, compared to free VCR. However, targeting of liposomes with a furin-binding peptide (TmR) did not further increase VCR accumulation in tumors, nor the therapeutic effect. We next selected peptides with greater affinity to RMS (F3), and nanobodies targeting FGFR4, highly specific for RMS. In vitro binding of liposomes to RMS could be dramatically increased by these ligands. The in vivo efficacy is under evaluation in an orthotopic model of RMS.

Prof. Dr. Giuseppe De Rosa - University of Naples, Federico II, Italy

Lipid self-assembling nanoparticle for RNA delivery


RNA delivery represents the main challenge for the development of RNA-based therapeutics. The approval of RNA-based vaccines against COVID-19 underlined the role of the lipid nanoparticles (LNP) for developing innovative therapeutical approaches. However, the poor physical stability of LNP requires low temperatures for storage and transport. In this context, lipid self-assembling nanoparticle (SANP) can represent an alternative as platform for RNA delivery. Lipid SANP formulations have shown remarkable biocompatibility, high RNA encapsulation efficiency, and enhanced intracellular release. Furthermore, SANP have been designed to be prepared at room temperature immediately before use by simple mixing of three components, namely, calcium/phosphate dispersion, RNA and cationic liposomes. By using this approach, the RNA could be stored and used in a lyophilized form, which ensures greater stability against degradation compared to freezing. SANP have been successful used to deliver miRNA and siRNA in the treatment of tumors with two different RNA-based strategies. As example, siRNA anti-praja2 have been successfully delivered in glioblastoma leading to significant inhibition of tumor growth; on the other hand, a miR603/R221 has been used to enhance the efficacy of temozolomide, in the treatment of glioblastoma. The use of SANP encapsulating mRNA for vaccination purpose is under evaluation.