title: Development and characterization of nanostructured mists with potential for actively targeting poorly water-soluble compounds into the lungs.
abstract: OBJECTIVE
  To formulate nanoemulsions (NE) with potential for delivering poorly water-soluble drugs to the lungs.
  
  
  METHODS
  A self nanoemulsifying composition consisting of cremophor RH 40, PEG 400 and labrafil M 2125 CS was selected after screening potential excipients. The solubility of carbamazepine, a poorly water-soluble drug, was tested in the formulation components. Oil-in-water (o/w) NEs were characterized using dynamic light scattering, electrophoretic light scattering, transmission electron microscopy (TEM) and differential scanning calorimetry. NEs were nebulized into a mist using a commercial nebulizer and characterized using laser diffraction and TEM. An aseptic method was developed for preparing sterile NEs. Biocompatibility of the formulation was evaluated on NIH3T3 cells using MTT assay. In vitro permeability of the formulation was tested in zebra fish eggs, HeLa cells, and porcine lung tissue.
  
  
  RESULTS
  NEs had neutrally charged droplets of less than 20 nm size. Nebulized NEs demonstrated an o/w nanostructure. The mist droplets were of size less than 5 μm. Sterility testing and cytotoxicity results validated that the NE was biocompatible and sterile. In vitro tests indicated oil nanodroplets penetrating intracellularly through biological membranes.
  
  
  CONCLUSIONS
  The nanoemulsion mist has the potential for use as a pulmonary delivery system for poorly water-soluble drugs.
authors.affiliation: Department of Pharmacy Practice College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, Ohio, USA. jerry.nesamony@utoledo.edu
authors.forename: Jerry
authors.initials: J
authors.lastname: Nesamony
authors.forename: Ashish
authors.initials: A
authors.lastname: Kalra
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Majrad
authors.forename: Sai Hanuman Sagar
authors.initials: SH
authors.lastname: Boddu
authors.forename: Rose
authors.initials: R
authors.lastname: Jung
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Williams
authors.forename: Alaina M
authors.initials: AM
authors.lastname: Schnapp
authors.forename: Surya M
authors.initials: SM
authors.lastname: Nauli
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Kalinoski
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002220:Carbamazepine / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004655:Emulsions; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D012995:Solubility; D013499:Surface Properties; D013552:Swine; D014867:Water / Q000737:chemistry*; D015027:Zebrafish
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D004655:Emulsions; D014867:Water; D002220:Carbamazepine