POLY(DIETHYLMETHYLIDENE MALONATE) NANOPARTICLES AS PRIMAQUINE DELIVERY SYSTEM TO LIVER

Five analogs of dialkylmethylidene malonate (DAMM) were synthesized with the aim of designing liver primaquine (PQ)-delivery nanoparticles. The diethyl derivative, diethylmethylidene malonate (DEMM), was polymerized in 0.1 M aqueous phosphate buffer and proved to be efficient in adsorbing PQ diphosphate. However, desorption of the entrapped drug was very low. The toxicity in NMRI female mice of the empty and PQ-loaded nanoparticles and of the free PQ diphosphate showed that drug-free nanoparticles were more toxic than PQ-bound nanoparticles whose toxicity was not significantly different from that of free PQ diphosphate. Administration in a single intraperitoneal injection of the free PQ diphosphate, free poly(DEMM) nanoparticles and PQ-loaded poly(DEMM) nanoparticles to Plasmodium berghei infected female NMRI mice showed a higher increased life span index (ILS) related with the PQ-loaded nanoparticles.