title: Elucidating the guest-host interactions and complex formation of praziquantel and cyclodextrin derivatives by (13)C and (15)N solid-state NMR spectroscopy.
abstract: Praziquantel is the drug of choice to treat several parasitic infections including the neglected tropical disease schistosomiasis. Due to its low aqueous solubility, cyclodextrins have been tested as potential host candidates to prepare praziquantel inclusion complexes with improved solubility. For the first time, the interactions of praziquantel with β-cyclodextrin and β-cyclodextrin derivatives (methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin) were investigated using high resolution solid-state NMR spectroscopy. The results of this work confirmed that solid-state NMR experiments provided structural characterization, demonstrating the formation of inclusion complexes most probably with PZQ adopting an anti conformation, also the most likely in amorphous raw PZQ. Further information on the interaction of praziquantel with methyl-β-cyclodextrin was obtained from proton rotating-frame relaxation time measurements, sensitive to kilohertz-regime motions but modulated by spin-diffusion. Evidences were presented in all cases for praziquantel complexation through the aromatic ring. In addition, 1:2 drug:carrier molar ratio appears to be the most probable and therefore suitable stoichiometry to improve pharmaceutical formulations of this antischistosomal drug.
authors.affiliation: IQUIR-CONICET, Suipacha 531, Rosario 2000, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Arrúa
authors.affiliation: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, Portugal.
authors.forename: M João G
authors.initials: MJ
authors.lastname: Ferreira
authors.affiliation: IQUIR-CONICET, Suipacha 531, Rosario 2000, Argentina; Área Técnica Farmacéutica, Facultad de Cs. Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, Rosario 2000, Argentina. Electronic address: csalomon@fbioyf.unr.edu.ar.
authors.forename: Claudio J
authors.initials: CJ
authors.lastname: Salomon
authors.affiliation: CQE, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisboa 1049-001, Portugal. Electronic address: teresa.nunes@tecnico.ulisboa.pt.
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Nunes
mesh_terms: D003505:Cyclodextrins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011223:Praziquantel / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D003505:Cyclodextrins; D011223:Praziquantel
keywords: Inclusion complex; Praziquantel; Schistosomiasis disease; Solid-state NMR; β-cyclodextrin derivatives