Novel 1-indanone Thiosemicarbazone Antiviral Candidates: Aqueous Solubilization and Physical Stabilization by Means of Cyclodextrins



To investigate cyclodextrin-mediated solubilization and physical stabilization of novel 1-indanone thiosemicarbazone (TSC) candidate drugs that display extremely high self-aggregation and precipitation tendency in water.


TSC/CD complexes were produced by co-solvent method, and TSC/CD phase-solubility diagrams were obtained by plotting TSC concentration as a function of increasing CD concentration. Size, size distribution, and zeta-potential of the different TSC/CD complexes and aggregates were fully characterized by dynamic light scattering. The morphology of the structures was visualized by atomic force microscopy.


Results indicated the formation of Type A inclusion complexes; the solubility of different TSCs was enhanced up to 215 times. The study of physical stability revealed that, as opposed to free TSCs that self-aggregate, crystallize, and precipitate in water very rapidly, complexed TSCs remain in solution for at least 1 week. On the other hand, a gradual size growth was observed. This phenomenon stemmed from the self-aggregation of the TSC/CD complex.


1-indanone TSC/CD inclusion complexes improved aqueous solubility and physical stability of these new drug candidates and constitute a promising technological approach towards evaluation of their activity against the viruses hepatitis B and C.

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R.J. Glisoni thanks the Ph.D. scholarship of CONICET. AS, AM and DC are staff members of CONICET. The authors thank Dr. Gloria Bonetto (Universidad Nacional de Córdoba, Córdoba, Argentina) for 1D-NMR analysis and Dr. Daniel R. Vega (Departamento Física de la Materia Condensada, CNEA, Buenos Aires, Argentina) for X-ray analysis.

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Correspondence to Alejandro Sosnik.

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Glisoni, R.J., Chiappetta, D.A., Moglioni, A.G. et al. Novel 1-indanone Thiosemicarbazone Antiviral Candidates: Aqueous Solubilization and Physical Stabilization by Means of Cyclodextrins. Pharm Res 29, 739–755 (2012).

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  • 1-indanone thiosemicarbazone antiviral candidates
  • inclusion complexes
  • native and modified cyclodextrins
  • self-assembly
  • water-solubilization