Development of inclusion complex based on cyclodextrin and oxazolidine derivative

• Main Authors: Rafael Ramos Silva (Author), Cézar Augusto da Cruz Amorim (Author), Maria do Carmo Alves Lima (Author), Marcelo Montenegro Rabello (Author), Marcelo Zaldini Hernandes (Author), Moacyr Jesus Barreto de Melo Rêgo (Author), Maira Galdino da Rocha Pitta (Author), Maria Danielly Lima de Oliveira (Author), César Augusto Souza de Andrade (Author)
• Format: Book
• Published: Universidade de São Paulo, 2023-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Abstract Oxazolidine derivatives (OxD) have been described as third-line antibiotics and antitumoral agents. The inclusion complexes based on cyclodextrin could improve the solubility and bioavailability of these compounds. A novel synthetic OxD was used, and its inclusion complexes were based on 2-hydroxy-beta-cyclodextrin (2-HPβCD). We conducted an in silico study to evaluate the interaction capacity between OxD and 2-HPβCD. Characterization studies were performed through scanning electron microscopy (SEM), Fourier-transformed infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), X-ray diffraction (XRD), and thermal analyses. A kinetic study of the OxD was performed, including a cytotoxicity assay using peripheral blood mononuclear cells (PBMCs). The maximum increment of solubility was obtained at 70 mM OxD using 400 mM 2-HPβCD. SEM analyses and FTIR spectra indicated the formation of inclusion complexes. 1H-NMR presented chemical shifts that indicated 1:1 stoichiometry. Different thermal behaviors were obtained. The pharmacokinetic profile showed a short release time. Pure OxD and its inclusion complex did not exhibit cytotoxicity in PBMCs. In silico studies provided a foremost insight into the interactions between OxD and 2-HPβCD, including a higher solubility in water and an average releasing profile without toxicity in normal cells.

Item Description

2175-9790
10.1590/s2175-97902023e22009