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Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility.
Szabó, Zoltán-István; Orbán, György; Borbás, Eniko; Csicsák, Dóra; Kádár, Szabina; Fiser, Béla; Dobó, Máté; Horváth, Péter; Kiss, Eszter; Budai, Lívia; Dobos, Judit; Pálla, Tamás; Orfi, László; Völgyi, Gergely; Tóth, Gergo.
Afiliación
  • Szabó ZI; Department of Pharmaceutical Industry and Management, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Gh. Marinescu 38, RO-540139, Targu Mures, Romania.
  • Orbán G; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Borbás E; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Muegyetem rakpart 3., Budapest, H-1111, Hungary.
  • Csicsák D; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Kádár S; Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Muegyetem rakpart 3., Budapest, H-1111, Hungary.
  • Fiser B; Computational Molecular Design Research Group, Institute of Chemistry, Faculty of Materials Science and Engineering, University of Miskolc, H-3515, Egyetemváros-Miskolc, Hungary.
  • Dobó M; Ferenc Rákóczi II. Transcarpathian Hungarian Institute, Beregszász, Transcarpathia, Ukraine.
  • Horváth P; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Kiss E; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Budai L; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Dobos J; Department of Pharmaceutics, Semmelweis University, Hogyes Endre u. 7, Budapest, H-1092 Hungary.
  • Pálla T; Vichem Chemie Research Ltd, Hermann O. utca 15, H-1022, Budapest, Hungary.
  • Orfi L; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Völgyi G; Department of Pharmaceutical Chemistry, Semmelweis University, Hogyes E. u. 9, Budapest H-1092, Hungary.
  • Tóth G; Vichem Chemie Research Ltd, Hermann O. utca 15, H-1022, Budapest, Hungary.
Heliyon ; 7(7): e07581, 2021 Jul.
Article en En | MEDLINE | ID: mdl-34355087
Pomalidomide (POM), a potent anticancer thalidomide analogue was characterized in terms of cyclodextrin complexation to improve its aqueous solubility and maintain its anti-angiogenic activity. The most promising cyclodextrin derivatives were selected by phase-solubility studies. From the investigated nine cyclodextrins - differing in cavity size, nature of substituents, degree of substitution and charge - the highest solubility increase was observed with sulfobutylether-ß-cyclodextrin (SBE-ß-CD). The inclusion complexation between POM and SBE-ß-CD was further characterized with a wide variety of state-of-the-art analytical techniques, such as nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), circular dichroism spectroscopy, fluorescence spectroscopy as well as X-ray powder diffraction method (XRD). Job plot titration by NMR and the AL-type phase-solubility diagram indicated 1:1 stoichiometry in a liquid state. Complementary analytical methods were employed for the determination of the stability constant of the complex; the advantages and disadvantages of the different approaches are also discussed. Inclusion complex formation was also assessed by molecular modelling study. Solid state complexation in a 1:1 M ratio was carried out by lyophilization and investigated by IR and XRD. The complex exhibited fast-dissolution with immediate release of POM, when compared to the pure drug at acidic and neutral pH. Kinetic analysis of POM release from lyophilized complex shows that Korsmeyer-Peppas and Weibull model described the best the dissolution kinetics. The cytotoxicity of the complex was tested against the LP-1 human myeloma cell line which revealed that supramolecular interactions did not significantly affect the anti-cancer activity of the drug. Overall, our results suggest that the inclusion complexation of POM with SBE-ß-CD could be a promising approach for developing more effective POM formulations with increased solubility.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2021 Tipo del documento: Article País de afiliación: Rumanía Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2021 Tipo del documento: Article País de afiliación: Rumanía Pais de publicación: Reino Unido