Cyclodextrin Derivatives as Modulators for Enhanced Drug Delivery from Niosome Membrane: A Fluorescence Correlation Spectroscopy and Isothermal Titration Calorimetry Approach

Designing efficient drug delivery systems for optimum therapeutic outcomes and minimum adverse effects remains a pivotal focus in pharmaceutical research. Understanding the nature of interactions between drugs and drug carriers and the drug-release mechanism are the key aspects for the development of effective delivery systems. This work presents a detailed investigation into the intricate interactions between niosomes and the drug Phenosafranin (PSF), and the subsequent release induced by a variety of cyclodextrins (CDs) employing a multifaceted approach. Ensemble average spectroscopic and single molecular level investigations based on fluorescence correlation spectroscopy (FCS), are employed to explore the binding interactions of PSF with the niosome membrane. Subsequently, the release of the drug was studied by disrupting the niosome structure using various CDs, and their efficacy was accessed through steady-state and time-resolved photophysical responses. FCS experiments provided precise insights into the binding and drug release process at the single-molecule level through the variation in translational and diffusion characteristics of the drug. Additionally, isothermal titration calorimetric (ITC) investigations further revealed the thermodynamics governing the CD-niosome host:guest interactions and the varying potential of different CDs in disrupting the niosome to release the drug which were further validated by electron microscopy and confocal fluorescence microscopy analyses. A broader analysis of niosomes prepared with various nonionic surfactants highlighted the influence of cavitand size and structure on the interaction with different niosome constituents. This comprehensive analysis sheds light on the complex interplay of these components and their interactions, providing insights into drug delivery systems and their potential therapeutic applications.