title: Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination.
abstract: OBJECTIVE
  p-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.
  
  
  METHODS
  Ex-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.
  
  
  RESULTS
  HR-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.
  
  
  CONCLUSIONS
  Taken together, data indicate that p-tertbutylcalix[4]arene nanoemulsion is both effective and safe formulation to use on skin for radio-decontamination.
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Navneet
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Ojha
authors.affiliation: Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi, Sector 3, Pushp Vihar, New Delhi 110017, India.
authors.forename: Dharam Pal
authors.initials: DP
authors.lastname: Pathak
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110054, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Goel
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences, Brig. S. K. Mazumdar Road, Delhi 110054, India. Electronic address: rksharmadrl@yahoo.com.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D047250:Calixarenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D003666:Decontamination / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007456:Iodine Isotopes / Q000302:isolation & purification; D007554:Isotopes / Q000302:isolation & purification; D008297:Male; D051381:Rats; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption; D013793:Thallium / Q000302:isolation & purification
chemical_list: D004655:Emulsions; D007456:Iodine Isotopes; D007554:Isotopes; C000613820:p-tertbutylcalix(4)arene; D047250:Calixarenes; D013793:Thallium
keywords: CBRN; Human skin fibroblast; ICPMS; Radioactive contaminants