Pharmaceutical Research

, Volume 29, Issue 3, pp 739–755 | Cite as

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

  • Romina J. Glisoni
  • Diego A. Chiappetta
  • Albertina G. Moglioni
  • Alejandro SosnikEmail author
Research Paper



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.


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



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.

Supplementary material

11095_2011_599_MOESM1_ESM.doc (68 kb)
Table SI (DOC 68 kb)
11095_2011_599_MOESM2_ESM.doc (46 kb)
Table SII (DOC 46 kb)
11095_2011_599_MOESM3_ESM.doc (62 kb)
Fig. S1 (DOC 66 kb)
11095_2011_599_MOESM4_ESM.doc (70 kb)
Fig. S2 (DOC 70 kb)
11095_2011_599_MOESM5_ESM.doc (52 kb)
Fig. S3 (DOC 51 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Romina J. Glisoni
    • 1
    • 2
  • Diego A. Chiappetta
    • 1
    • 2
  • Albertina G. Moglioni
    • 2
    • 3
  • Alejandro Sosnik
    • 1
    • 2
    Email author
  1. 1.The Group of Biomaterials & Nanotechnology for Improved Medicines (BIONIMED) Department of Pharmaceutical Technology Faculty of Pharmacy & BiochemistryUniversity of Buenos AiresBuenos AiresArgentina
  2. 2.National Science Research Council (CONICET)Buenos AiresArgentina
  3. 3.Department of PharmacologyFaculty of Pharmacy & Biochemistry University of Buenos AiresBuenos AiresArgentina

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