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Nonclinical safety evaluation of boric acid and a novel borate-buffered contact lens multi-purpose solution, Biotrue™ multi-purpose solution

Published:November 09, 2010DOI:https://doi.org/10.1016/j.clae.2010.06.010

      Abstract

      Multipurpose solutions (MPS) often contain low concentrations of boric acid as a buffering agent. Limited published literature has suggested that boric acid and borate-buffered MPS may alter the corneal epithelium; an effect attributed to cytotoxicity induced by boric acid. However, this claim has not been substantiated. We investigated the effect of treating cells with relevant concentrations of boric acid using two cytotoxicity assays, and also assessed the impact of boric acid on corneal epithelial barrier function by measuring TEER and immunostaining for tight junction protein ZO-1 in human corneal epithelial cells. Boric acid was also assessed in an in vivo ocular model when administered for 28 days. Additionally, we evaluated Biotrue multi-purpose solution, a novel borate-buffered MPS, alone and with contact lenses for ocular compatibility in vitro and in vivo. Boric acid passed both cytotoxicity assays and did not alter ZO-1 distribution or corneal TEER. Furthermore, boric acid was well-tolerated on-eye following repeated administration in a rabbit model. Finally, Biotrue multi-purpose solution demonstrated good ocular biocompatibility both in vitro and in vivo. This MPS was not cytotoxic and was compatible with the eye when administered alone and when evaluated with contact lenses. We demonstrate that boric acid and a borate-buffered MPS is compatible with the ocular environment. Our findings provide evidence that ocular effects reported for some borate-buffered MPS may be incorrectly attributed to boric acid and are more likely a function of the unique combination of ingredients in the MPS formulation tested.

      Abbreviations:

      MPS (multi-purpose solutions), ZO-1 (zonula occuldens protein-1), HCEpiC (human corneal epithelial cells), USP (United States Pharmacopeia), MEM (Eagle's Minimum Essential Medium), HDPE (high density polyethylene), TEER (transepithelial electrical resistance), NBF (neutral buffered formalin), PCA (perchloric acid), PBS (phosphate buffered saline), BBS (borate buffered saline), SC (0.9% sodium chloride USP solution), SO (sesame oil), PV (PureVision), AVA (Acuvue Advance), CAE (corneal anterior epithelium), CS (corneal stroma), CPE (corneal posterior epithelium), ISO (International Organization for Standardization)

      Keywords

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      References

        • Christie C.L.
        • Meyler J.G.
        Contemporary contact lens care products.
        Cont Lens Anterior Eye. 1997; 20: S11
        • 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
        • Horwath-Winter J.
        • Simon M.
        • Kolli H.
        • Trummer G.
        • Schmut O.
        Cytotoxicity evaluation of soft contact lens care solutions on human conjunctival fibroblasts.
        Ophthalmologica. 2004; 218: 385-389
        • Mowrey-McKee M.
        • Sills A.
        • Wright A.
        CIBA Vision Corporation. Comparative cytotoxicity potential of soft contact lens care regimens.
        CLAO J. 2002; 28: 160-1644
        • Santodomingo-Rubido J.
        • Mori O.
        • Kawaminami S.
        Cytotoxicity and antimicrobial activity of six multipurpose soft contact lens disinfecting solutions.
        Ophthalmic Physiol Opt. 2006; 26: 476-482
        • Wright A.
        • Mowrey-McKee M.
        Comparative cytotoxicity potential of soft contact lens care products.
        J Toxicol Cutan Ocul Toxicol. 2005; : 53-64
        • Cavet M.E.
        • Harrington K.L.
        • VanDerMeid K.R.
        • Ward K.E.
        • Zhang J.Z.
        Comparison of the effect of multipurpose contact lens solutions on the viability of cultured corneal epithelial cells.
        Cont Lens Anterior Eye. 2009; 32: 171-175
      1. Final safety assessment of sodium borate and boric acid. J Am Coll Toxicol 1983;7:87–125.

        • Imayasu M.
        • Shiraishi A.
        • Ohashi Y.
        • Shimada S.
        • Cavanagh H.D.
        Effects of multipurpose solutions on corneal epithelial tight junctions.
        Eye Cont Lens. 2008; 34: 50-55
        • Imayasu M.
        • Shimizu H.
        • Shimada S.
        • Suzuki T.
        • Cavanagh H.D.
        Effects of Multipurpose contact lens care solutions on adhesion of Pseudomonas aeruginosa to corneal epithelial cells.
        Eye Cont Lens. 2009; 35: 98-104
        • Chapman J.M.
        • Cheeks L.
        • Green K.
        Interactions of benzalkonium chloride with soft and hard contact lenses.
        Arch Ophthalmol. 1990; : 244-246
        • Christensen M.T.
        • Barry J.R.
        • Turner F.D.
        Five-minute removal of soft lenses prevents most absorption of a topical ophthalmic solution.
        CLAO J. 1998; : 27-31
        • Havener W.H.
        Wetting Agents.
        in: Havener W.H. Ocular pharmacology. C.V. Mosby, St. Louis1983
        • McCanna D.J.
        • Harrington K.L.
        • Driot J.Y.
        • Ward K.W.
        • Tchao R.
        Use of a human corneal epithelial cell line for screening the safety of contact lens care solutions in vitro.
        Eye Cont Lens. 2008; 34: 6-12
        • Guess W.L.
        • Rosenbluth S.A.
        • Schmidt B.
        • Autian J.
        Agar diffusion method for toxicity screening of plastics on cultured cell monolayers.
        J Pharm Sci. 1965; 54: 1545-1547
      2. United States Pharmacopeia 31, National Formulary 31 (USP), General chapter 87, biological reactivity tests, in vitro; 2009.

        • Kimura K.
        • Teranishi S.
        • Fukuda K.
        • Kawamoto K.
        • Nishida T.
        Delayed disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-alpha in a manner dependent on NF-kappaB.
        Invest Ophthalmol Vis Sci. 2008; 49: 565-571
        • McDonald T.
        • Shadduck J.
        Eye irritation.
        in: Marzulli F.N. Maibach H.I. Advances in modern toxicology. Volume 4: dermatotoxicology and pharmacology. Hemisphere Publishing Corp., Washington, DC1977: 579-582
        • Draize J.H.
        • Woodard G.
        • Calvery H.O.
        Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes.
        J Pharmacol Exp Ther. 1944; : 7
      3. International Organization for Standardization (ISO) 9394. Ophthalmic optics – contact lenses and contact lens care products – determination of biocompatibility by ocular study with rabbits; 1998.

        • Vinardell M.P.
        • Mitjans M.
        Alternative methods for eye and skin irritation tests: an overview.
        J Pharm Sci. 2008; 97: 46-59
      4. The U.S. Food and Drug Evaluation and Research. Office of generic drugs. Division of Labeling and Program Support. Updated January 6; 2010.

        • Snibson G.R.
        • Greaves J.L.
        • Soper N.D.
        • Tiffany J.M.
        • Wilson C.G.
        • Bron A.J.
        Ocular surface residence times for artificial tear solutions.
        Cornea. 1992; 11: 288-293
      5. Asgharian B. Low molecular weight amino alcohols in ophthalmic compositions. Patent US 7,045,095 B2; 16 May 2006.

      6. Wanda Richard G, Heiler David J. Treatment of contact lenses with aqueous solution including phosphonic compounds. Patent US 5,858,937; 12 January 1999.

        • Pfister R.R.
        • Burstein N.
        The effects of ophthalmic drugs, vehicles, and preservatives on corneal epithelium: a scanning electron microscope study.
        Invest Ophthal. 1976; 15: 246-259
        • North-Root H.
        • Yackovich F.
        • Demetrulias J.
        • Gacula M.
        • Heinze J.E.
        Evaluation of an in vitro cell toxicity test using rabbit corneal cells to predict the eye irritation potential of surfactants.
        Toxicol Lett. 1982; 14 (1982): 207-212
        • Jackson E.M.
        • Hume R.D.
        • Wallin R.F.
        The agarose diffusion method for ocular irritancy screening: cosmetic products, part II.
        J Toxicol Cutan Ocul Toxicol. 1988; 7: 187-194
        • Ikarashi Y.
        • Tsuchiya T.
        • Nakamura A.
        Comparison of three in vitro assays to determine the ocular toxicity of detergent, oil, and organic solvents.
        J Toxicol Cutan Ocul Toxicol. 1993; 12: 15-24
        • Pflugfelder S.C.
        • de Paiva C.S.
        • Li D.Q.
        • Stern M.E.
        Epithelial-immune cell interaction in dry eye.
        Cornea. 2008; 27: 9-11
        • Lin M.C.
        • Polse K.A.
        Hypoxia, overnight wear, and tear stagnation effects on the corneal epithelium: data and proposed model.
        Eye Cont Lens. 2007; 33: 378-381
        • Lipener C.
        A randomized clinical comparison of Opti-free express and ReNu MultiPLUS multipurpose lens care solutions.
        Adv Ther. 2009; 26: 435-446
        • Sorbara L.
        • Peterson R.
        • Woods C.
        • Fonn D.
        Multipurpose disinfecting solutions and their interactions with a silicone hydrogel lens.
        Eye Cont Lens. 2009; 35: 92-97
        • Garofalo R.J.
        • Dassanayake N.
        • Carey C.
        • Stein J.
        • Stone R.
        • David R.
        Corneal staining and subjective symptoms with multipurpose solutions as a function of time.
        Eye Cont Lens. 2005; : 166-174