Mechanistic insights into encapsulation and release of drugs in colloidal niosomal systems: biophysical aspects

Abstract

Vesicular systems such as niosomes provide an alternative to improve drug delivery systems. The efficiency of a drug delivery vehicle is strongly dependent on its components which decide its interaction with partitioned drug(s) and locus of site of partitioning. A quantitative understanding of the physical chemistry underlying partitioning of drugs in complex systems of self-assemblies such as niosomes is scarcely available. In order to obtain quantitative mechanistic insights into partitioning and release of drugs [mitoxantrone (MTX) and ketoprofen (KTP)] in systems of niosomes, we have employed ultrasensitive calorimetry, spectroscopy and microscopy to establish correlations between functionality and energetics which could provide guidance towards rational drug design and choice of suitable non-ionic surfactant-based drug delivery vehicles. Electron microscopy and dynamic light scattering (DLS) methods were used for characterization and assessing the morphology of niosomes. We present here a calorimetry-based approach in assessing the partitioning of the anticancer drugs mitoxantrone and ketoprofen in niosomes and their release to human serum albumin (HSA) employing isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) and comparison with equilibrium dialysis. The thermodynamic signatures and kinetics of release were analyzed to obtain insights into the role of the functional groups on the drugs in the partitioning process. The assessment of thermal and conformational stability of proteins during drug binding and the effect of drug delivery vehicles on proteins is also crucial. To assess these effects, DSC studies on HSA in the presence and absence of drugs and niosomes were also performed. Finally, the efficacy of the system to impact the cell viability of the MDA-MB-231 triple-negative breast carcinoma cell line was analysed using MTT assay.