GLISONI Romina Julieta
congresos y reuniones científicas
Dermatan sulfate/chitosan polyelectrolyte complex for targeting agents to vessel wall.
VASTA M.; FUNEZ F.; GLISONI RJ.; SOSNIK A.; CALABRESE GC.
Mar del Plata, Argentina
Congreso; Reunión Conjunta 2016 SAIC-SAI-SAFE NANOMED-AR; 2016
There is still no pharmaceutical treatment that directly targets the blood vessel wall instead of just controlling the risk factors in cardiovascular disease. We has produced polyelectrolyte complexes (PECs) by a simple and reproducible polyelectrolyte complexation method between low molecular mass dermatan sulfate (LMMDS) (polyanionic polysaccharide) and chitosan (CS) (polycationic polysaccharide). We have reported that the uptake of PECs by microvascular endothelial cells was specific. The aim of the present work was to analyze the binding of PECs to normal and injured endothelial cells. PECs were prepared employing CS labeled with fluorescein isothiocyanate (FITC-PECs). The size (Dh), size distribution (PDI) and zeta potential (Z-potential) of PECs were determined by dynamic light scattering (DLS). Murine heart microvascular cells (H5V) were incubated with FITC-PECs (10 μg/mL, according to their LMMDS concentration) for 30, 60, 120 and 180 min in the absence or in the presence of 37.5 μg/mL LMMDS. Lipopolysaccharide treatment (1.5 μg/ml) was performed for 3 hs to induce cell injury. Fluorescence images from a minimum of 10 fields were collected from each sample. FITC-PECs, produced by the ionotropic gelification method, exhibited a main size distribution of 644 ± 81 nm (98%) and an average PDI value of 0.398 ± 0.043 (n= 3). After lipopolysaccharide treatment PECs uptake increased around three times compared with control cells (n=3). H5V cells presented a homogeneous green dotted signal after incubating with PECs for 30-60 min; restricted to certain areas after 120-180 min. The presence of a high but nontoxic dose of LMMDS blocked the uptake of FITC-PECs at all incubation time. Our in vitro results show that (1) the uptake of CS-LMMDS PECs was increased in injured endothelium and (2) LMMDS could be associated to the specific binding to endothelial cell what suggest that CD44 receptor could be responsible for the specific binding.