Reduced nephrotoxicity of epichlorohydrin-crosslinked β-cyclodextrin nanoparticles (βCDNPs) and its enhanced binding with hydrophobic compounds

Abstract

This paper explores the development and characterization of epichlorohydrin-crosslinked β-cyclodextrin nanoparticles (βCDNPs) for drug delivery, focusing on their interaction with hydrophobic drugs and biocompatibility. We synthesized βCDNPs using β-cyclodextrin (βCD) and epichlorohydrin (ECH). Our study assessed the biocompatibility and safety of βCDNPs, particularly in avoiding nephrotoxicity commonly associated with βCD, by examining their interaction with cholesterol and conducting survival analyses in mice at various dosing concentrations. Additionally, we highlight the advantages of using diffusion-ordered NMR spectroscopy (DOSY) to determine the enhanced binding constants of βCDNPs with hydrophobic compounds, in comparison with the solubility method, Job plot analysis, and isothermal titration calorimetry (ITC). We demonstrated the enhanced binding capacity of βCDNPs compared to βCD alone and established the polymerization of βCD as a significant factor in this enhancement. Our findings suggest that βCDNPs show promise as drug delivery systems due to their improved solubility, stability, and safety profiles.