Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders

Recent progress in the science of complex coacervation

“…(10) This approach has been applied to a variety of systems using both ITC and fluorescence-based binding assays to provide information on the details of charge-driven binding, 280,282 with experimental evidence correlating well with results from simulations. 283 While these binding studies were performed under very dilute conditions to avoid multi-body interactions, a number of studies have reported on both bulk complex coacervation 2,[12][13][14][15]76,[284][285][286][287][288][289][290][291] and microphase separation 73,[292][293][294][295][296][297][298][299][300][301] involving globular proteins and polyelectrolytes. Of particular note from these studies is the identification of a critical charge content necessary for complex coacervation to occur between a protein and an oppositely-charged polymer.…”

Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders

“…Cell culture conditions : HEK293T cells (CRL‐3216, ATCC) were routinely maintained in RPMI medium supplemented with 10% foetal bovine serum (Life Technologies, Paisley, UK), 2 m M L‐Glutamine (Life Technologies), 1 X Non‐essential aminoacids (Life Technologies), 1X antimycotic‐antibiotic (Life Technologies) solution at 37°C and 5% CO 2 . Mouse endothelial aortic cells (MAEC) were isolated from descending aorta of GLA deficient mice (GlatmKul1) at the ICTS NANBIOSIS (U20) following procedures previously established procedures (Giannotti et al., 2016; Nazarenus et al., 2015; Shu et al., 2005). Endothelial origin of isolated cells was confirmed by CD105 staining (12‐1051, eBioscience) and flow cytometry (FacScalibur, Becton Dickinson).…”

“…In this scenario, the use of nanotechnological approaches increasing the efficiency of recombinant enzymes and targeting them to specific cell types is regarded as a powerful approach to introduce new effective therapies for LSDs (Muro, 2010). Different types of nanoparticles have been tested as vehicles for ERT in Fabry disease including liposomes, (Cabrera et al., 2016) chitosan polyelectrolytes (Giannotti et al., 2016) and polystyrene nanoparticles (Hsu et al., 2014). Moreover, other nanocarriers from a biological origin, such as nanoparticles made of albumin and 30Kc19 protein (Lee et al., 2016) have also been studied at the preclinical level.…”

Chitosan-Based Nanomaterials for Drug Delivery

“…The CS-MET could serve as a gene delivery vector and anti-diabetes prodrug, which would collapse to release the MET and gene due to proton pumping effects in the body. Similarly, Giannotti et al designed a highly versatile polyelectrolyte complex to improve the enzyme replacement therapy of lysosomal storage disorders, and fluorescein molecules were attached to the modified CS backbone to improve drug delivery [ 66 ]. These studies show that modification of CS and its derivatives have greatly contributed to the wide exploration and application for targeted drug delivery in the developments of medical devices.…”