Physicochemical characterization, solubility enhancement, molecular docking, and antibacterial activity of inclusion complexes of naproxen/β-cyclodextrin derivatives: A comparative study

Abstract

Naproxen (NAP) is a nonsteroidal anti-inflammatory drug. The aim of this work is to enhance the aqueous solubility and dissolution rate of naproxen (NAP) by forming an inclusion complex with β-cyclodextrin derivatives (β-CDs) such as 2-hydroxypropyl-β-cyclodextrin (Hβ-CD), methyl-β-cyclodextrin (Mβ-CD), and sulfated-β-cyclodextrin (Sβ-CD). UV–vis and fluorescence spectroscopic techniques were applied to examine the interaction of the β-CDs:NAP inclusion complexes in pH 7.4 buffer solution. The 1:1 stoichiometry of the β-CDs:NAP inclusion complexes was confirmed by the Benesi-Hildebrand method. The solid-state β-CDs:NAP inclusion complexes were obtained by co-precipitation and were characterized by FTIR, XRD, SEM, and TGA-DSC analyses. Phase solubility diagrams were calculated linearly from the slope and intercept, where the maximum apparent stability constants (Ks) were found to be 1123, 1261, and 1131 M−1 for Hβ-CD, Mβ-CD, and Sβ-CD respectively, indicating formation of the β-CDs:NAP inclusion complexes. Molecular docking was used to systematically validate formation of the β-CDs:NAP inclusion complexes. The antibacterial activity of the β-CDs:NAP inclusion complexes was described here for the first time, and it was shown that the activity of NAP against Staphylococcus aureus (91 ± 0.12%) and Escherichia coli (87 ± 0.14%) was remarkably enhanced by encapsulation in the β-cyclodextrin derivatives. The prepared solid β-CDs:NAP inclusion complexes are highly stable in aqueous media, where the antibacterial activity can be enhanced by increasing the solubility of NAP.