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Vanessa Andres-Guerrero, Blanca Arango-Gonzalez, Eva Ramsay, Mengmeng Zong, Beatriz de las Heras, George Mihov, Aylvin Dias, Arto Urtti, Marius Ueffing, Rocio Herrero-Vanrell; Polyesteramide Microspheres As Carriers In Ophthalmology. In Vitro Toxicity In Macrophages, ARPE-19 Cells And An Organotypic Culture Of Retina. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4900.
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Amino acid based polyesteramides (PEAs) are a new family of synthetic biodegradable polymers based on α-amino acids, aliphatic dicarboxylic acids and aliphatic α-ω diols. The aim of this study was to evaluate the suitability of PEA microspheres (Ms), in terms of toxicity, to be used as carriers in ophthalmology.
PEA Ms were prepared following an emulsion-solvent evaporation technique. Ms were characterized by morphology, mean particle size, particle size distribution and molar mass. In vitro tolerance was performed with two techniques: (1) MTT in a peritoneal macrophages cell line (RAW 264.7) and a retinal pigment epithelial cell line (ARPE-19), in which cells were exposed to PEA Ms (0.001-2 mg/ml) for 20 hours and 5 hours, respectively, and (2) TUNEL assay, combined with conventional histology, in short and a long term organotypic cultures (7 and 20 days, respectively) of rats’ retinas (0.125-1 mg Ms). PLGA Ms were used as control.
Spherical PEA Ms with no pores and smooth surface were produced (mean particle size= 14.96 ± 6.4 µm; Mn= 48.3 ± 3.7 kDa). PEA microparticles showed no signs of toxicity in the MTT assay (cell viability > 80%), using both macrophages and ARPE-19 cells. Retinas in organotypic cultures treated with 0.125 and 0.625 mg/ml PEA Ms and PLGA Ms in short and long term cultures did not show signs of toxicity. The TUNEL values were similar to the observed in untreated cultures. On the other hand, retinas treated with a high concentration of PEA Ms (1mg/ml), in long term cultures, showed cellular disorganization and internalization of particles. Similar histologic changes were observed in control retinas treated with PLGA Ms.
Biodegradable PEA Ms are potentially useful to develop new controlled drug delivery systems for treating ophthalmic diseases affecting the back of the eye.
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