GLISONI Romina Julieta
congresos y reuniones científicas
Innovative nanotechnological platform based on polyelectrolytes of dermatan sulfate and chitosan for the treatment of vascular diseases.
BLACHMAN A.; FUNEZ F.; SAAVEDRA SL.; CAMPERI S.; GLISONI RJ.; CALABRESE GC.
Caba, Buenos Aires, Argentina
Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017
Vascular diseases, particularly atherosclerosis, are one of the principal causes of morbid-mortality in the world. Recently, we reported the production of polyelectrolyte complexes (PECs) by a simple and reproducible method between low molecular mass dermatan sulfate (DS) (polyanionic polysaccharide) and chitosan (CS) (polycationic polysaccharide), which specifically interact with injured endothelial cells through CD44 receptor. The aim of the present work was to employ these complexes as a drug delivery platform of an anti-inflammatory egg white ovotransferrin-derived tripeptide Ile-Arg-Trp, (IRW). The tripeptide was obtained on solid phase employing Fmoc chemistry in Rink-Amide-MBHA resin. Then, protector groups from the lateral chains were cleavage and IRW were released by trifluoracetic acid. DS/CS PECs-IRW were prepared by polyelectrolyte complexation method in the presence of IRW (5, 25, 50 µM). The size (Dh), size distribution (PDI) and zeta potential (Z-potential) of PECs were determined by dynamic light scattering (DLS). The presence of free IRW in particle suspensions was evaluated by spectroscopy at 390nm. Unloaded DS/CS PECs exhibited a Dh(nm) (±SD): 729 (11), which represent 93%, with PDI (±SD): 0.322 (0.055) and Z-potential (mV) (±SD): .4 (0.8) (n= 3). DS/CS PECs- IRW (5 µM) exhibited Dh(nm) (±SD): 509 (77.2), which represent 84%, with PDI (±SD): 0.495 (0.114) and Z-potential (mV) (±SD): 29.9 (2.55) (n= 2). And, DS/CS PECs- IRW (50 µM) exhibited Dh(nm) (±SD): 550 (131.2), which represent 100%, with PDI (±SD): 0.475 (0.021) and Z-potential (mV) (±SD): 35.6 (1.62) (n= 2). In all cases, the presence of free IRW was undetectable. In conclusion, DS guarantee PECs specific uptake by endothelial cells; while CS limits lysosomal degradation and support the gradual release of IRW inside the cell. Ongoing studies are oriented to explore the capacity of DS/CS PECs-IRW to modulate the endothelial inflammatory response associated with the early stage of vascular diseases.