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Abstract #45734 Published in IGR 13-2
The use of mucoadhesive polymers to enhance the hypotensive effect of a melatonin analogue, 5-MCA-NAT, in rabbit eyes
Andres-Guerrero V; Molina-Martinez IT; Pera A; de las Heras B; Pintor J; Herrero-Vanrell RInvestigative Ophthalmology and Visual Science 2011; 52: 1507-1515
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-MCANAT 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 (mu)M) 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.
R. Herrero-vanrell. Departments of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Madrid 28040, Spain. Email: rociohv@farm.ucm.es
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)