Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Complutense University, Madrid, Spain.
Invest Ophthalmol Vis Sci. 2011 Mar 18;52(3):1507-15. doi: 10.1167/iovs.10-6099.
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.
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.
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.
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.
5-甲氧基羰基氨基-N-乙酰色胺（5-MCA-NAT，褪黑素受体激动剂）可降低新西兰白兔和青光眼猴的眼内压（IOP）。本研究旨在评估纤维素衍生物（其中一些具有生物粘附特性）的存在是否增强了 5-MCA-NAT 的降压作用，以及这些制剂是否能被眼表面很好地耐受。
用丙二醇（0.275%）、低和中粘度的羧甲基纤维素（CMC，0.5%和 1.0%）和羟丙基甲基纤维素（0.3%）制备制剂。通过 HPLC 定量测定 5-MCA-NAT（100 μM）。通过 MTT 法在人角膜缘上皮细胞和正常人结膜细胞中评估体外耐受性。通过兔眼生物显微镜和共焦显微镜分析体内耐受性。通过测量兔眼 8 小时内的 IOP 评估眼内压降低效果。
所有制剂均表现出良好的体外和体内耐受性。在 CMC 中粘度 0.5%的制剂中，5-MCA-NAT 降低 IOP 的效果最明显（最大 IOP 降低 30.27%），其作用持续约 7 小时。
在制剂中使用具有生物粘附性的聚合物可增强 5-MCA-NAT 的降压作用，这些制剂适用于眼表面，并且在长期治疗中对眼睛具有保护作用。将 5-MCA-NAT 与生物粘附性聚合物联合使用是治疗眼高压和青光眼的一种有效策略。
