Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination

Abstract

Aimsp-tertbutylcalix[4]arene loaded nanoemulsion has been designed, characterized and evaluated for skin decontamination of radionuclides of interest in nuclear and radiological emergencies. Further, nanoemulsion was evaluated for Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity. Materials and methodsEx-vivo skin complexation studies were conducted using High-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS). Skin studies at dermal and cyto-dermal level have been carried out using techniques such as florescence microscopy, Differential scanning calorimetry (DSC), Flow cytometry, Confocal microscopy, Prestoblue and Comet assay. Key findingsHR-SF-ICPMS study confirmed >95% complexation of surrogate nuclides of thallium and Iodine applied on excised rat skin mounted over Franz diffusion cell. Temporal analysis of aliquots obtained from Franz diffusion cell using UV–Vis absorption spectroscopy indicated that only 3.37% of formulation permeates through the skin. Skin penetration study of rhodamine 123 nanoemulsion carried out using florescence microscopy confirmed that formulation remains localised in epidermis of rat skin. DSC data confirmed skin compatibility of nanoemulsion, as no lipid extraction was observed from skin. In-vitro cell viability and cellular uptake assays performed on human skin fibroblasts prove no cellular uptake and cytotoxic effects. Comet assay, cell cycle arrest, and apoptosis-inducing mechanistic studies prove that prepared nanoemulsion is safe at cellular level. SignificanceTaken together, data indicate that p-tertbutylcalix[4]arene nanoemulsion is both effective and safe formulation to use on skin for radio-decontamination.