Speaker
Mr
Jannik Pedersen
(Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark)
Description
Fabry disease is a lysosomal storage disorder, where the lack of α-Galactosidase A (GLA) causes accumulation of glycosphingolipids leading to damage of the kidneys, heart and nervous system. With current treatments, free GLA is injected intravenously in patients causing instability of GLA, high immunogenicity, and low bioavailability. To overcome this, liposomes has been developed that can encapsulate GLA and improve the performance. Further development of the liposomes is necessary and currently being done to archive perfect control of the assembly process. The liposomes consists of several different components that can alter the size, polydispersity and structure of the liposomes, and characterization of different formulations is therefore important in the development of new liposomal formulations. We have used an In-house small-angle X-ray scattering (SAXS) setup to get information on the average liposomal structure in presence of different lipids. We use a para crystalline model (Guinier, A. (1963). X-ray Diffraction, San Francisco: Freeman) with a finite number of layers and disorder between layers, while a set of Gaussians is used to describe the cross-section profile of the lipid bilayer. Scattering from GLA contributes to the total signal and is in the model added to the scattering from the bilayers, so that an estimate of the amount of GLA can be obtained. Using the model for fitting the data, we are able to follow incorporation of GLA in the liposomes and changes in bilayer thickness as well as changes in the amount of multi-lamellar structures and bilayer ordering. The incorporation of GLA in the formulations correlates well with the results from the SAXS data, and it is also observed that the distance between layers is increased when larger molecules are incorporated in the liposomes. The number of bilayers determined with SAXS correlates well with that seen with cryo-TEM. Altogether, the SAXS data can give us a lot of information on the structure, composition and polydispersity of the liposomes. We also used static and dynamic light scattering to obtain information on the size and polydispersity of the samples and can use this in characterizing the homogeneity of the samples. This information is important for further development of new liposomal drug formulations and will be an important tool in the design of liposomes that has a low polydispersity, are stable and can help in improving the treatment of Fabry Disease.
This project has received funding from the European Union’s Horizon 2020 research and innovation programmer under the grant agreement No 720942.
Primary author
Mr
Jannik Pedersen
(Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark)
Co-authors
Mr
Carsten Pedersen
(Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark)
Prof.
Dganit Danino
(Biotechnology & Food Engineering Department, Technion, Israel Institute of Technology, Haifa 3200000, Israel)
Mr
Henrik Sørensen
(Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark)
Prof.
Jan Skov Pedersen
(Department of Chemistry and Interdisciplinary Nanoscience Center (iNANO) Aarhus University Gustav Wieds Vej 14 Building 1590-252 8000 Aarhus C, Denmark)
Prof.
Nora Ventosa
(Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Esfera UAB , Campus UAB s/n; E-08193 Cerdanyola del Vallès, Spain. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Nanomol group , Campus UAB s/n; E-08193Cerdanyola del Vallès, Spain)
Dr
Solene Passemard
(Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Esfera UAB , Campus UAB s/n; E-08193 Cerdanyola del Vallès, Spain. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Nanomol group , Campus UAB s/n; E-08193Cerdanyola del Vallès, Spain)
