Publication: The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes
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2011-03
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Association for Research in Vision and Ophthalmology (ARVO)
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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.
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1. Quigley HA Broman AT . The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–267.
2. Curtis C Lo E Ooi L Bennett L Long J . Factors affecting compliance with eye drop therapy for glaucoma in a multicultural outpatient setting. Contemp Nurse. 2009;31:121–128.
3. Kholdebarin R Campbell RJ Jin YP Buys YM . Multicenter study of compliance and drop administration in glaucoma. Can J Ophthalmol. 2008;43:454–461.
4. Gray TA Orton LC Henson D Harper R Waterman H . Interventions for improving adherence to ocular hypotensive therapy. Cochrane Database Syst Rev. 2009;CD006132.
5. Kalavala M Statham BN . Allergic contact dermatitis from timolol and dorzolamide eye drops. Contact Dermatitis. 2006;54:345.
6. Quiralte J Florido F de San Pedro BS . Allergic contact dermatitis from carteolol and timolol in eyedrops. Contact Dermatitis. 2000;42:245.
7. Camras CB Toris CB Tamesis RR . Efficacy and adverse effects of medications used in the treatment of glaucoma. Drugs Aging. 1999;15:377–388.
8. Martone G Frezzotti P Tosi GM . An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. Am J Ophthalmol. 2009;147:725–735 e721.
9. Baffa Ldo P Ricardo JR Dias AC . Tear film and ocular surface alterations in chronic users of antiglaucoma medications. Arq Bras Oftalmol. 2008;71:18–21.
10. Baudouin C Riancho L Warnet JM Brignole F . In vitro studies of antiglaucomatous prostaglandin analogues: travoprost with and without benzalkonium chloride and preserved latanoprost. Invest Ophthalmol Vis Sci. 2007;48:4123–4128.
11. Bai T Huang J Wang W . Short-term comparative study of the effects of preserved and unpreserved topical levofloxacin on the human ocular surface. Cutan Ocul Toxicol. 2010;29:247–253.
12. Baudouin C de Lunardo C . Short-term comparative study of topical 2% carteolol with and without benzalkonium chloride in healthy volunteers. Br J Ophthalmol. 1998;82:39–42.
13. Kahook MY Noecker RJ . Comparison of corneal and conjunctival changes after dosing of travoprost preserved with sofzia, latanoprost with 0.02% benzalkonium chloride, and preservative-free artificial tears. Cornea. 2008;27:339–343.
14. Brasnu E Brignole-Baudouin F Riancho L Guenoun JM Warnet JM Baudouin C . In vitro effects of preservative-free tafluprost and preserved latanoprost, travoprost, and bimatoprost in a conjunctival epithelial cell line. Curr Eye Res. 2008;33:303–312.
15. Bartlett JD . Ophthalmic Drug Facts: Facts and Comparisons. 21st ed. Hagerstown, MD: Lippincott Williams & Wilkins; 2009:371–407.
16. Baudouin C Labbe A Liang H Pauly A Brignole-Baudouin F . Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010;29:312–334.
17. Mundorf T Noecker RJ Earl M . Ocular hypotensive efficacy of brimonidine 0.15% as adjunctive therapy with latanoprost 0.005% in patients with open-angle glaucoma or ocular hypertension. Adv Ther. 2007;24:302–309.
18. Franks W . Ocular hypotensive efficacy and safety of brinzolamide ophthalmic suspension 1% added to travoprost ophthalmic solution 0.004% therapy in patients with open-angle glaucoma or ocular hypertension. Curr Med Res Opin. 2006;22:1643–1649.
19. Manni G Denis P Chew P . The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. J Glaucoma. 2009;18:293–300.
20. Martinez A Sanchez-Salorio M . A comparison of the long-term effects of dorzolamide 2% and brinzolamide 1%, each added to timolol 0.5%, on retrobulbar hemodynamics and intraocular pressure in open-angle glaucoma patients. J Ocul Pharmacol Ther. 2009;25:239–248.
21. Arnold JJ Choksi Y Chen X . Eyedrops containing SA9000 prodrugs result in sustained reductions in intraocular pressure in rabbits. J Ocul Pharmacol Ther. 2009;25:179–186.
22. Andres-Guerrero V Alarma-Estrany P Molina-Martinez IT Peral A Herrero-Vanrell R Pintor J . Ophthalmic formulations of the intraocular hypotensive melatonin agent 5-MCA-NAT. Exp Eye Res. 2009;88:504–511.
23. Wang RF Podos SM Mittag TW Yokoyoma T . Effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes. Exp Eye Res. 2005;80:629–632.
24. Hosseini A Lattanzio FA Williams PB Tibbs D Samudre SS Allen RC . Chronic topical administration of WIN-55-212-2 maintains a reduction in IOP in a rat glaucoma model without adverse effects. Exp Eye Res. 2006;82:753–759.
25. Higashiyama M Inada K Ohtori A Tojo K . Improvement of the ocular bioavailability of timolol by sorbic acid. Int J Pharm. 2004;272:91–98.
26. von der Ohe N Stark M Mayer H Brewitt H . How can the bioavailability of timolol be enhanced?—a pharmacokinetic pilot study of novel hydrogels. Graefes Arch Clin Exp Ophthalmol. 1996;234:452–456.
27. Aggarwal D Pal D Mitra AK Kaur IP . Study of the extent of ocular absorption of acetazolamide from a developed niosomal formulation, by microdialysis sampling of aqueous humor. Int J Pharm. 2007;338:21–26.
28. Saettone MF Giannaccini B Teneggi A Savigni P Tellini N . Vehicle effects on ophthalmic bioavailability: the influence of different polymers on the activity of pilocarpine in rabbit and man. J Pharm Pharmacol. 1982;34:464–466.
29. Patton TF Robinson JR . Ocular evaluation of polyvinyl alcohol vehicle in rabbits. J Pharm Sci. 1975;64:1312–1316.
30. Ludwig A . The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev. 2005;57:1595–1639.
31. May JA Dantanarayana AP Zinke PW McLaughlin MA Sharif NA . 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. J Med Chem. 2006;49:318–328.
32. Markovskaya A Crooke A Guzman-Aranguez AI Peral A Ziganshin AU Pintor J . Hypotensive effect of UDP on intraocular pressure in rabbits. Eur J Pharmacol. 2008;579:93–97.
33. Chien FY Wang RF Mittag TW Podos SM . Effect of WIN 55212-2, a cannabinoid receptor agonist, on aqueous humor dynamics in monkeys. Arch Ophthalmol. 2003;121:87–90.
34. Pang IH Moll H McLaughlin MA . Ocular hypotensive and aqueous outflow-enhancing effects of AL-3037A (sodium ferri ethylenediaminetetraacetate). Exp Eye Res. 2001;73:815–825.
35. Miguez JM Recio J Sanchez-Barcelo E Aldegunde M . Changes with age in daytime and nighttime contents of melatonin, indoleamines, and catecholamines in the pineal gland: a comparative study in rat and Syrian hamster. J Pineal Res. 1998;25:106–115.
36. Arendt J . Melatonin and the pineal gland: influence on mammalian seasonal and circadian physiology. Rev Reprod. 1998;3:13–22.
37. Luboshitzky R Yanai D Shen-Orr Z Israeli E Herer P Lavie P . Daily and seasonal variations in the concentration of melatonin in the human pineal gland. Brain Res Bull. 1998;47:271–276.
38. Lundmark PO Pandi-Perumal SR Srinivasan V Cardinali DP Rosenstein RE . Melatonin in the eye: implications for glaucoma. Exp Eye Res. 2007;84:1021–1030.
39. Alarma-Estrany P Pintor J . Melatonin receptors in the eye: location, second messengers and role in ocular physiology. Pharmacol Ther. 2007;113:507–522.
40. Wiechmann AF Summers JA . Circadian rhythms in the eye: the physiological significance of melatonin receptors in ocular tissues. Prog Retin Eye Res. 2008;27:137–160.
41. Katavisto M . The diurnal variations of ocular tension in glaucoma. Acta Ophthalmol Suppl. 1964;78(suppl):71–130.
42. Henkind P Leitman M Weitzman E . The diurnal curve in man: new observations. Invest Ophthalmol. 1973;12:705–707.
43. Kitazawa Y Horie T . Diurnal variation of intraocular pressure in primary open-angle glaucoma. Am J Ophthalmol. 1975;79:557–566.
44. Ido T Tomita G Kitazawa Y . Diurnal variation of intraocular pressure of normal-tension glaucoma: influence of sleep and arousal. Ophthalmology. 1991;98:296–300.
45. Pintor J Martin L Pelaez T Hoyle CH Peral A . Involvement of melatonin MT(3) receptors in the regulation of intraocular pressure in rabbits. Eur J Pharmacol. 2001;416:251–254.
46. Mailliet F Ferry G Vella F . Characterization of the melatoninergic MT3 binding site on the NRH:quinone oxidoreductase 2 enzyme. Biochem Pharmacol. 2005;71:74–88.
47. Alarma-Estrany P Crooke A Pintor J . 5-MCA-NAT does not act through NQO2 to reduce intraocular pressure in New-Zealand white rabbit. J Pineal Res. 2009;47:201–209.
48. Vincent L Cohen W Delagrange P Boutin JA Nosjean O . Molecular and cellular pharmacological properties of 5-methoxycarbonylamino-N-acetyltryptamine (MCA-NAT): a nonspecific MT3 ligand. J Pineal Res. 2010;48:222–229.
49. Serle JB Wang RF Peterson WM Plourde R Yerxa BR . Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on intraocular pressure in glaucomatous monkey eyes. J Glaucoma. 2004;13:385–388.
50. Pintor J Pelaez T Hoyle CH Peral A . Ocular hypotensive effects of melatonin receptor agonists in the rabbit: further evidence for an MT3 receptor. Br J Pharmacol. 2003;138:831–836.
51. FDA, Ophthalmic demulcents, Part 349.12. Subheading of ophthalmic drug products for over-the-counter human use, 21CFR349 (2006) Available at http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/UCM135691.pdf.
52. Morgan PB Soh MP Efron N . Corneal surface temperature decreases with age. Cont Lens Anterior Eye. 1999;22:11–13.
53. Acosta MC Berenguer-Ruiz L Garcia-Galvez A Perea-Tortosa D Gallar J Belmonte C . Changes in mechanical, chemical, and thermal sensitivity of the cornea after topical application of nonsteroidal anti-inflammatory drugs. Invest Ophthalmol Vis Sci. 2005;46:282–286.
54. Scudiero DA Shoemaker RH Paull KD . Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. Cancer Res. 1988;48:4827–4833.
55. Liu Y Peterson DA Kimura H Schubert D . Mechanism of cellular 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction. J Neurochem. 1997;69:581–593.
56. Gipson IK Spurr-Michaud S Argueso P Tisdale A Ng TF Russo CL . Mucin gene expression in immortalized human corneal-limbal and conjunctival epithelial cell lines. Invest Ophthalmol Vis Sci. 2003;44:2496–2506.
57. Saarinen-Savolainen P Jarvinen T Araki-Sasaki K Watanabe H Urtti A . Evaluation of cytotoxicity of various ophthalmic drugs, eye drop excipients and cyclodextrins in an immortalized human corneal epithelial cell line. Pharm Res. 1998;15:1275–1280.
58. Wilson WS Duncan AJ Jay JL . Effect of benzalkonium chloride on the stability of the precorneal tear film in rabbit and man. Br J Ophthalmol. 1975;59:667–669.
59. De Saint Jean M Brignole F Bringuier AF Bauchet A Feldmann G Baudouin C . Effects of benzalkonium chloride on growth and survival of Chang conjunctival cells. Invest Ophthalmol Vis Sci. 1999;40:619–630.
60. Efron N . Grading scales for contact lens complications. Ophthalmic Physiol Opt. 1998;18:182–186.
61. Efron N Morgan PB Katsara SS . Validation of grading scales for contact lens complications. Ophthalmic Physiol Opt. 2001;21:17–29.
62. Guenoun JM Baudouin C Rat P Pauly A Warnet JM Brignole-Baudouin F . In vitro study of inflammatory potential and toxicity profile of latanoprost, travoprost, and bimatoprost in conjunctiva-derived epithelial cells. Invest Ophthalmol Vis Sci. 2005;46:2444–2450.
63. Detry-Morel M . Side effects of glaucoma medications. Bull Soc Belge Ophtalmol. 2006;27–40.
64. Baudouin C Liang H Hamard P . The ocular surface of glaucoma patients treated over the long-term expresses inflammatory markers related to both T-helper 1 and T-helper 2 pathways. Ophthalmology. 2008;115:109–115.
65. Rossi GC Tinelli C Pasinetti GM Milano G Bianchi PE . Dry eye syndrome-related quality of life in glaucoma patients. Eur J Ophthalmol. 2009;19:572–579.
66. Ayaki M Yaguchi S Iwasawa A Koide R . Cytotoxicity of ophthalmic solutions with and without preservatives to human corneal endothelial cells, epithelial cells and conjunctival epithelial cells. Clin Exp Ophthalmol. 2008;36:553–559.
67. Schuman JS . Antiglaucoma medications: a review of safety and tolerability issues related to their use. Clin Ther. 2000;22:167–208.
68. Sherwood MB Grierson I Millar L Hitchings RA . Long-term morphologic effects of antiglaucoma drugs on the conjunctiva and Tenon's capsule in glaucomatous patients. Ophthalmology. 1989;96:327–335.
69. Pisella PJ Pouliquen P Baudouin C . Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication. Br J Ophthalmol. 2002;86:418–423.
70. Fechtner RD Godfrey DG Budenz D Stewart JA Stewart WC Jasek MC . Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29:618–621.
71. Davies NM Farr SJ Hadgraft J Kellaway IW . Evaluation of mucoadhesive polymers in ocular drug delivery, I: viscous solutions. Pharm Res. 1991;8:1039–1043.
72. Mundada AS Avari JG . In situ gelling polymers in ocular drug delivery systems: a review. Crit Rev Ther Drug Carrier Syst. 2009;26:85–118.
73. Kimura H Ogura Y . Biodegradable polymers for ocular drug delivery. Ophthalmologica. 2001;215:143–155.
74. Davies NM Farr SJ Hadgraft J Kellaway IW . Evaluation of mucoadhesive polymers in ocular drug delivery, II: polymer-coated vesicles. Pharm Res. 1992;9:1137–1144.
75. Herrero-Vanrell R Fernandez-Carballido A Frutos G Cadorniga R . Enhancement of the mydriatic response to tropicamide by bioadhesive polymers. J Ocul Pharmacol Ther. 2000;16:419–428.
76. Benedetto DA Shah DO Kaufman HE . The instilled fluid dynamics and surface chemistry of polymers in the preocular tear film. Invest Ophthalmol. 1975;14:887–902.
77. Johnston TP Dias CS Mitra AK . Mucoadhesive polymers in ophthalmic drug delivery. Ophthalmic Drug Deliv Syst. 2003;13:409–435.