Polymeric nanoparticles from carbohydrate-derived polytriazoles for cilostazol delivery

RIVAS, MARÍA VERÓNICA; MUSIKANT, DANIEL; DÍAZ PEÑA, ROCÍO; ALVAREZ, DANIELA; PELAZZO, LUCIANA; ROSSI, EZEQUIEL; ERREA, MARÍA I.; VARELA, OSCAR; PEREZ, OSCAR E.; KOLENDER, ADRIANA A.

San Pablo - on line

Simposio; 30th International Carbohydrate Symposium (ICS2022; 2022

Polytriazoles derived from carbohydrate derivatives combine the abundance, defined stereochemistry and functionalization of renewable carbohydrates with the low toxicity and biological activities of triazole moieties. The use of different protecting strategies on the carbohydrate hydroxyl groups allows the modulation of properties on the resulting materials. In our laboratory, we have synthesized poly(amide-triazole)s and poly(ester-triazole)s from D-galactose, prepared from -azido--alkyne monomeric units with the secondary hydroxyl groups protected as 1,2-diisopropylidene derivatives, by copper assisted azide-alkyne cycloaddition (CuAAC) and copper free (CuFAAC) polymerizations.1,2 Polymeric nanoparticles (NP) prepared from natural and synthetic polymers have been applied successfully for drug delivery. Herein we describe the application of the D-galactose-derived polytriazoles for the synthesis of polymeric NP, with poly(vinyl alcohol) by emulsification/evaporation method. The NP were applied for the encapsulation of cilostazol (CLZ), an active ingredient currently applied in the treatment of intermittent claudication. However, CLZ is associated to undesired side-effects due to low solubility in aqueous systems. CLZ was efficiently encapsulated in NP of 200-nm diameter size (DLS). The analysis of the biological activity, by means of a metalloprotease (MMP) in vitro model, demonstrated that NP containing CLZ exerted a significant regulation of MMP-9 at least up to 25 M and showed better CC50 performance than free CLZ.