title: New administration model of trans-chalcone biodegradable polymers for the treatment of experimental leishmaniasis.
abstract: The present study was designed to investigate a new administration model and the antileishmanial activity of a semi-synthetic chalcone, benzylideneacetophenone (trans-chalcone). The antileishmanial activity of this product was first tested in vitro against promastigotes of L. braziliensis, L. tropica, L. infantum and L. amazonensis. An in vivo experiment was carried out using subcutaneous administration of trans-chalcone and implants of synthetic biodegradable polymers, polylactic acid (PLA) and polylactic/glycolic acid (PLGA). This compound showed potent inhibitory effects on the growth of all Leishmania strains examinated. Subcutaneous administration of trans-chalcone at a single dose of 4 mg/kg of body weight reduced lesion development in mice infected with L. amazonensis. A similar inhibition of the lesion growth in mice treated with trans-chalcone and pentamidine was observed. PLA and PGLA implants of trans-chalcone at 4 mg/kg were administered to mice infected with L. amazonensis. PLGA implants induced a highest reduction in the lesion size (31.25%) than PLA implants (10.75%). Treatment in vitro with trans-chalcone at IC50, completely inhibited the pathogenicity of this parasite in vivo. The development of this model provides a new practical technique for delivering drugs and can be useful for experimental leishmaniasis treatment.
authors.affiliation: Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Tenerife, Islas Canarias, Spain. jpinero@ull.es
authors.forename: Jose
authors.initials: J
authors.lastname: Piñero
authors.forename: Rosane M
authors.initials: RM
authors.lastname: Temporal
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Silva-Gonçalves
authors.forename: I A
authors.initials: IA
authors.lastname: Jiménez
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Bazzocchi
authors.forename: Alexis
authors.initials: A
authors.lastname: Oliva
authors.forename: Antonio
authors.initials: A
authors.lastname: Perera
authors.forename: Leonor L
authors.initials: LL
authors.lastname: Leon
authors.forename: Basilio
authors.initials: B
authors.lastname: Valladares
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D002599:Chalcone / Q000008:administration & dosage* / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D019344:Lactic Acid; D007892:Leishmania braziliensis; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010419:Pentamidine / Q000627:therapeutic use; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013997:Time Factors
chemical_list: D000981:Antiprotozoal Agents; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D002599:Chalcone; D010419:Pentamidine