Carbohydrate-derived polytriazole nanoparticles enhance anti-inflammatory activity of cilostazol

RIVAS, MARIA VERONICA; MUSIKANT, DANIEL; DIAZ PEÑA, ROCIO; ÁLVAREZ, DANIELA;; PELAZZO, LUCIANA; ROSSI, EZEQUIEL; MARTÍNEZ, KARINA; ERREA, MARÍA; PÉREZ, OSCAR; VARELA, OSCAR; KOLENDER, ADRIANA

ACS Omega

American Chemical Society

Lugar: 1155 16th St. NW, Washington, DC 20036; Año: 2022

2470-1343

Poly(amide-triazole) and poly(ester-triazole) synthesized from D-galactose as arenewable resource were applied for the synthesis of nanoparticles (NPs) by theemulsification/solvent evaporation method. The NPs were characterized as stable, sphericalparticles, and none of their components, including the stabilizer poly(vinyl alcohol), werecytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficientencapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for thetreatment of intermittent claudication, which is associated to undesired side-effects. In thiscontext, the nanoencapsulation of CLZ was expected to improve its therapeutic administration.The carbohydrate-derived polymeric NPs were designed taking into account that the triazolerings of the polymer backbone could have attractive interactions with the tetrazole ring of CLZ.The activity of the nanoencapsulated CLZ was measured using a matrix metalloproteinasemodel, in a lipopolysaccharide-induced inflammation system. Interestingly, the encapsulateddrug exhibited enhanced anti-inflammatory activity in comparison with the free drug. The resultsare very promising, since the stable, non-cytotoxic NP systems efficiently reduced theinflammation response at low CLZ doses. In summary, the NPs were obtained through aninnovative methodology that combines a carbohydrate-derived synthetic polymer, designed tointeract with the drug, ease of preparation, adequate biological performance, andenvironmentally friendly production.