Romina J Glisoni1,2, Diego A Chiappetta1,2, Albertina G Moglioni2,3, Alejandro Sosnik4,5. 1. The Group of Biomaterials & Nanotechnology for Improved Medicines (BIONIMED) Department of Pharmaceutical Technology Faculty of Pharmacy & Biochemistry, University of Buenos Aires, 956 Junín St., 6th Floor, Buenos Aires, CP1113, Argentina. 2. National Science Research Council (CONICET), Buenos Aires, Argentina. 3. Department of Pharmacology, Faculty of Pharmacy & Biochemistry University of Buenos Aires, Buenos Aires, Argentina. 4. The Group of Biomaterials & Nanotechnology for Improved Medicines (BIONIMED) Department of Pharmaceutical Technology Faculty of Pharmacy & Biochemistry, University of Buenos Aires, 956 Junín St., 6th Floor, Buenos Aires, CP1113, Argentina. alesosnik@gmail.com. 5. National Science Research Council (CONICET), Buenos Aires, Argentina. alesosnik@gmail.com.
Abstract
PURPOSE: 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. METHODS: 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: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: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: 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. CONCLUSIONS:1-indanoneTSC/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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