A non-toxic inclusion complexation of loxoprofen with hydroxypropyl-β-cyclodextrin for complete solubility and anti-inflammatory efficacy

Abstract

In recent days, there has been a significant demand for drugs that are easily soluble, non-toxic, safe, and biocompatible for human use. Recently, active pharmaceutical ingredient (API) complexes with cyclodextrins (CDs) and their derivatives have gained considerable attention. In line with this trend, we have developed an inclusion complex material for loxoprofen using hydroxypropyl derivatives of beta-cyclodextrin (Hyd-β-CD). The formation of the complex between loxoprofen (LXP) and Hyd-β-CD has been confirmed through changes in absorbance and fluorescence intensity, indicating a 1:1 stoichiometric ratio. The addition of Hyd-β-CD significantly enhanced the solubility of LXP, reflecting successful complexation. Proton NMR and ROESY analyses show that the phenyl group of LXP resides within the cavity of the Hyd-β-CD. Further validation is provided by DFT orientations and their associated energy parameters. Cell viability studies indicate that the increased solubility of the inclusion complex (IC) improves the bioavailability of the drug, while toxicity tests show that our IC material does not induce toxicity in normal cells. Moreover, the anti-inflammatory efficacy of LXP is markedly enhanced in its IC form. These findings underscore the potential of IC in extending the application of LXP, especially in pharmaceuticals, where the enhanced stability and efficacy of natural active ingredients and anti-inflammatory agents are crucial.