title: Improvement of the oral praziquantel anthelmintic effect by cyclodextrin complexation.
abstract: Schistosomiasis is a parasitic disease which kills a half million people per year, all over the world. Praziquantel (PZQ) is the drug-of-choice for schistosomiasis because of its effectiveness, ease of administration, and low cost. However, poor solubility restricts its delivery, especially via the oral route. In this study, we describe beta-cyclodextrin (beta-CD) complexation as an alternative to improve the PZQ bioavailability. Physicochemical analysis were performed to characterize the inclusion complex formed between PZQ and beta-CD. Differential scanning calorimetry (DSC) thermograms and morphological analysis using scanning electronic microscopy (SEM) gave evidences of the complex formation. Diffusion NMR experiments allowed determination of the fraction of PZQ bound to beta-CD (37%) and the association constant (941 +/- 47 M(-1)). The in vivo evaluation of the complexation on the effect of PZQ was performed on mice infected with Schistosoma mansoni (BH strain); after 15 days of treatment with the PZQ:beta-CD complex the efficacy, evaluated by the number of remaining alive worms, was 99%, against 59% elicited by plain PZQ.
authors.affiliation: Department of Biochemistry, Institute of Biology, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Marcelo Bispo
authors.initials: MB
authors.lastname: de Jesus
authors.forename: Luciana de Matos Alves
authors.initials: Lde M
authors.lastname: Pinto
authors.forename: Leonardo Fernandes
authors.initials: LF
authors.lastname: Fraceto
authors.forename: Luiz Augusto
authors.initials: LA
authors.lastname: Magalhães
authors.forename: Eliana Maria
authors.initials: EM
authors.lastname: Zanotti-Magalhães
authors.forename: Eneida
authors.initials: E
authors.lastname: de Paula
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005260:Female; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011223:Praziquantel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000187:drug effects; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000871:Anthelmintics; D047392:beta-Cyclodextrins; D011223:Praziquantel; C031215:betadex