title: Nanomolar cationic dendrimeric sulfadiazine as potential antitoxoplasmic agent.
abstract: The high doses of sulfadiazine (SDZ), used in synergistic combination with pyrimethamine, are mainly responsible for severe side effects and discontinuation of toxoplasmosis treatments. In the search for new strategies that improve the efficacy of treatments with reduced doses of SDZ, we have determined the performance of cationic G4 (DG4) and anionic G4.5 (DG4.5) poly(amidoamine) (PAMAM) dendrimers to act as SDZ nanocarriers. Both dendrimers could efficiently load SDZ (SDZ-DG4 and SDZ-DG4.5) up to a ratio of 30 molecules SDZ per dendrimer molecule. The MTT assay on Vero and J774 cells showed no cytotoxicity for DG4.5 and its SDZ complex incubated between 0.03 and 33 microM of dendrimer concentration. On the other hand, DG4 and its SDZ complex resulted cytotoxic when incubated at dendrimer concentrations higher than 3.3 microM. Finally, complexes and empty dendrimers were in vitro tested against Vero cells infected with RH strain of Toxoplasma gondii along 4h of treatment. For SDZ-DG4.5 and DG4.5 to cause an infection decrease between 25 and 40%, respectively, a dendrimer concentration of 33 microM was required; however, SDZ-DG4 produced the highest infection decrease of 60% at 0.03 microM. These preliminary results, achieved with nanomolar doses of SDZ-DG4 as unique active principle, point to this complex as a suitable potential candidate for antitoxoplasmic therapy.
authors.affiliation: Laboratorio de Diseño de Estrategias de Targeting de Drogas (LDTD), Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 180, Bernal B1876BXD, Buenos Aires, Argentina.
authors.forename: M J
authors.initials: MJ
authors.lastname: Prieto
authors.forename: D
authors.initials: D
authors.lastname: Bacigalupe
authors.forename: O
authors.initials: O
authors.lastname: Pardini
authors.forename: J I
authors.initials: JI
authors.lastname: Amalvy
authors.forename: C
authors.initials: C
authors.lastname: Venturini
authors.forename: M J
authors.initials: MJ
authors.lastname: Morilla
authors.forename: E L
authors.initials: EL
authors.lastname: Romero
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival; D002522:Chlorocebus aethiops; D050091:Dendrimers; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D011073:Polyamines / Q000737:chemistry; D012995:Solubility; D013411:Sulfadiazine / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014122:Toxoplasma / Q000378:metabolism; D014123:Toxoplasmosis / Q000188:drug therapy*; D014709:Vero Cells
chemical_list: D002412:Cations; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011073:Polyamines; D013778:Tetrazolium Salts; D013844:Thiazoles; D013411:Sulfadiazine; C022616:thiazolyl blue