title: Optimum topical delivery of adrenergic agonists to oral mucosa vasculature.
abstract: OBJECTIVE
  Identify an orotopical vehicle to deliver an α-adrenergic vasoconstrictor to submucosal vasculature that is readily palatable to cancer/bone marrow transplant patients that suppresses chemo-radiotherapy-associated oral mucositis.
  
  
  METHODS
  A [(3)H] norepinephrine ligand binding assay was developed to quantify receptor binding in hamster oral mucosa. Vehicle components (alcohols, polyols, cellulose, PVP) were tested versus [(3)H] norepinephrine binding. Vehicle refinement was also done to mask phenylephrine bitter taste and achieve human subject acceptance. The optimized vehicle was tested with α-adrenergic active agents to suppress radiation-induced oral mucositis in mice.
  
  
  RESULTS
  The ligand binding assay quantified dose- and time-dependent, saturable binding of [(3)H] norepinephrine. An ethanol:glycerol:propylene glycol:water (6:6:8:80) vehicle provided the best delivery and binding. Further vehicle modification (flavoring and sucralose) yielded a vehicle with excellent taste scores in humans. Addition of phenylephrine, norepinephrine or epinephrine to the optimized vehicle and painting into mouse mouths 20 min before 19 Gy irradiation conferred significant suppression of the weight loss (P < 0.001) observed in mice who received oral vehicle.
  
  
  CONCLUSIONS
  We identified a highly efficient vehicle for the topical delivery of phenylephrine to the oral mucosa of both hamster and human subjects. This will enable its testing to suppress oral mucositis in an upcoming human clinical trial.
authors: McArdle Laboratory for Cancer Research, University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA.
authors: Cheryl M
authors: CM
authors: Soref
authors: William E
authors: WE
authors: Fahl
mesh_terms: D000287:Administration, Topical; D000322:Adrenergic Agonists / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D006224:Cricetinae; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051379:Mice; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000322:Adrenergic Agonists; D010656:Phenylephrine