Smart4fabry / News

Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method

Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients.
In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability.
Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease.
Through a risk analysis and a Design of Experiments (DoE), we obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.

More information can be found here

Impact of Chemical Composition on the Nanostructure and Biological Activity of α Galactosidase Loaded Nanovesicles for Fabry Disease Treatment

Fabry disease is a rare lysosomal storage disorder characterized by a deficiency of α-galactosidase A (GLA), a lysosomal hydrolase. The enzyme replacement therapy administering naked GLA shows several drawbacks including poor biodistribution, limited efficacy, and relatively high immunogenicity in Fabry patients. An attractive strategy to overcome these problems is the use of nanocarriers for encapsulating the enzyme. Nanoliposomes functionalized with RGD peptide have already emerged as a good platform to protect and deliver GLA to endothelial cells. However, low colloidal stability and limited enzyme entrapment efficiency could hinder the further pharmaceutical development and the clinical translation of these nanoformulations. Herein, the incorporation of the cationic miristalkonium chloride (MKC) surfactant to RGD nanovesicles is explored, comparing two different nanosystems-quatsomes and hybrid liposomes. In both systems, the positive surface charge introduced by MKC promotes electrostatic interactions between the enzyme and the nanovesicles, improving the loading capacity and colloidal stability. The presence of high MKC content in quatsomes practically abolishes GLA enzymatic activity, while low concentrations of the surfactant in hybrid liposomes stabilize the enzyme without compromising its activity. Moreover, hybrid liposomes show improved efficacy in cell cultures and a good in vitro/in vivo safety profile, ensuring their future preclinical and clinical development.

More information can be found here


Small drugs – Big considerations: How New Deal researchers are overcoming the challenges of scaling-up a potential IBD nanomedicine

A great chef could create an outstanding dish that revolutionizes cuisine – every time they prepare the recipe for two, it may come out perfect and impress everyone who tries it. However, they would probably struggle to reproduce the same show-stopper dish with the same flavour, texture and taste on a large scale when cooking for a crowd. Something similar happens when scientists develop a new drug: some of the desired characteristics of the medicine obtained in the laboratory at a small scale might be difficult to recreate when the same drug is manufactured in industrial quantities for the market.

More information can be found here

Nanomedicine comes of age: European researchers take nanotech-based therapies from the lab to the clinic

There are already more than 50 nanomedicine formulations in the market and over 400 currently in clinical trials, thanks to the unique versatility of these therapeutics compared to conventional drugs. Several European projects are developing nanomedicines in areas with unmet medical needs, such as Cupido (cardiovascular disease), B-Smart (neurodegenerative disorders), Smart-4-Fabry (Fabry disease) and New Deal (inflammatory bowel disease).

More information can be found here

14th Mediterranean Congress of Chemical Engineering

It is our pleasure to inform you that (virtual) oral communication under the tittle “Scale-up and Quality by Design application to the robust production of an enzyme-loaded liposomal formulation by DELOS-susp method” has been accepted for the 14th Mediterranean Congress of Chemical Engineering that will take place on 16-20th November 2020. The 10-minutes talk will be focused on the scale-up and the potential advantages of S4F technologies for the society.

More information can be found on

ETPN – European Technology Platform on Nanomedicine

ETPN2020 is the 15th annual event of the ETPN – European Technology Platform on Nanomedicine, to be held on Oct. 14-15, 2020, as a virtual event this year in the context of the COVID-19 pandemic.

“Translational issues in nanomedicine” Workshop will be held in the context of this event, on October 14 at 14:00 CET. New Deal, SMART4FABRY and other Horizon 2020 sister projects will participate on it.

Don’t miss this opportunity and join us. You can find more details and register here

“La Marató de TV3”: An effort of the Catalan civil society to support Research and Innovation in Health

In this occasion the “Marató de TV3: Minories que fan una Majoria”, is devoted to rare diseases. La Marató de TV3 is an annual telethon broadcast by Televisió de Catalunya and the Fundació La Marató de TV3 to raise funds for scientific research into diseases which are currently incurable

But La Marató de TV3 is more than just a fund-raising drive. It also informs the Catalan public about these diseases and explains the need for research aimed at preventing and curing them. Just as important as the money raised by the telethon are the scientific publications, the awareness-raising, and public education in scientific questions. Marató funded first research steps that afterwards crystalized in the Smart4Faby project. More information available at


On the 27th October, our colleague Judit Tomsen form ICMAB-CSIC-CIBER presented the advances for Fabry disease treatment obtained in the context of Smart4Fabry project at the XIII Science Festival in Barcelona. This event inclues more than 200 activities, and is intended to get Science and Technology closer to citizens and society, with a special focus in children and teenagers. This is an excellent way to make society aware of the efforts in Research and innovation at the EU level.

V Consortium meeting in Aarhus hosted by Aarhus University

SMART4FABRY consortium organized its V Consortium meeting in Aarhus (Denmark), kindly hosted by our partner Aarhus University. During two days, (2nd-3rd July), all the partners had an excellent opportunity to discuss last project results and decide the strategy for the next period, including a robust planning until the end of the project. Next meeting will be organized in January in Barcelona.