title: The use of mucoadhesive polymers to enhance the hypotensive effect of a melatonin analogue, 5-MCA-NAT, in rabbit eyes.
abstract: OBJECTIVE
  5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin receptor agonist) produces a clear intraocular pressure (IOP) reduction in New Zealand White rabbits and glaucomatous monkeys. The goal of this study was to evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence of cellulose derivatives, some of them with bioadhesive properties, as well as to determine whether these formulations were well tolerated by the ocular surface.
  
  
  METHODS
  Formulations were prepared with propylene glycol (0.275%), carboxymethyl cellulose (CMC, 0.5% and 1.0%) of low and medium viscosity and hydroxypropylmethyl cellulose (0.3%). Quantification of 5-MCA-NAT (100 μM) was assessed by HPLC. In vitro tolerance was evaluated by the MTT method in human corneal-limbal epithelial cells and normal human conjunctival cells. In vivo tolerance was analyzed by biomicroscopy and specular microscopy in rabbit eyes. The ocular hypotensive effect was evaluated measuring IOP for 8 hours in rabbit eyes.
  
  
  RESULTS
  All the formulations demonstrated good in vitro and in vivo tolerance. 5-MCA-NAT in CMC medium viscosity 0.5% was the most effective at reducing IOP (maximum IOP reduction, 30.27%), and its effect lasted approximately 7 hours.
  
  
  CONCLUSIONS
  The hypotensive effect of 5-MCA-NAT was increased by using bioadhesive polymers in formulations that are suitable for the ocular surface and also protective of the eye in long-term therapies. The use of 5-MCA-NAT combined with bioadhesive polymers is a good strategy in the treatment of ocular hypertension and glaucoma.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Andrés-Guerrero
authors.forename: Irene T
authors.initials: IT
authors.lastname: Molina-Martínez
authors.forename: Assumpta
authors.initials: A
authors.lastname: Peral
authors.forename: Beatriz
authors.initials: B
authors.lastname: de las Heras
authors.forename: Jesús
authors.initials: J
authors.lastname: Pintor
authors.forename: Rocío
authors.initials: R
authors.lastname: Herrero-Vanrell
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000187:drug effects; D004357:Drug Synergism; D019573:Epithelium, Corneal / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D014677:Pharmaceutical Vehicles; D011817:Rabbits; D044094:Receptors, Melatonin / Q000819:agonists; D013500:Surface Tension; D014363:Tryptamines / Q000494:pharmacology*; D014783:Viscosity
chemical_list: C413586:5-methoxycarbonylamino-N-acetyltryptamine; D000959:Antihypertensive Agents; D014677:Pharmaceutical Vehicles; D044094:Receptors, Melatonin; D014363:Tryptamines; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium