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The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes

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Andrés Guerrero, Vanessa and Molina Martínez, Irene T. and Peral Cerdá, Assumpta and De las Heras Polo, Beatriz and Pintor, Jesús and Herrero Vanrell, Mª Rocío (2011) The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes. Investigative ophthalmology & visual science, 52 . pp. 1507-1515. ISSN 1552-5783

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Official URL: http://dx.doi.org/10.1167/iovs.10-6099




Abstract

Purpose.: 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.


Item Type:Article
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Uncontrolled Keywords:Melatonin ; Polymer ; Eye
Subjects:Sciences > Chemistry > Chemistry, Organic
Medical sciences > Medicine > Ophtalmology
Medical sciences > Veterinary > Veterinary ophtalmology
ID Code:39522
Deposited On:21 Oct 2016 09:31
Last Modified:21 Oct 2016 09:31

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