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David C Paik, Anna Takaoka, Takayuki Nagasaki; Cosmetic preservatives as therapeutic corneal and scleral tissue cross-linking (TXL) agents: formaldehyde release studies.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4353.
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© ARVO (1962-2015); The Authors (2016-present)
Topical application of a chemical cross-linking agent provides an alternative/adjunct to photochemical cross-linking (CXL) for altering the tissue properties of the cornea and/or sclera. We are in search of the ideal cross-linking compounds that can “fix tissue, but spare the cells.” This has led to the use of formaldehyde-releasing agents (FARs), commonly found as preservatives in cosmetics, to serve as formaldehyde (FA) delivery agents, but with much less toxicity than free formaldehyde. This study was undertaken in order to understand the conditions that can modulate FA release. The information gained will help to translate this technology into clinical practice.
Three FARs, sodium hydroxymethyl glycinate (SMG), diazolidinyl urea (DAU) and 1,3-dimethylol-5,5-dimethylhydantoin (DMDM) were studied for their FA release characteristics using a chromotropic acid assay. The basic NIOSH (National Institute for Occupational Safety and Health) procedure was followed. Using this simple colorimetric assay, we studied the effects of concentration, pH (1-10), buffer type (0.1N HCl, 100mM NaHCO3, dH2O ) and time (up to 24hrs) on the release of free FA.
FA release was not impacted by either pH or solution type (including unbuffered water). The main determinant of release was dilution factor (concentration) in which maximal release (expressed as a percentage of expected release) was noted at the lowest concentrations (sub-millimolar). Nearly 100% release was shown for SMG (1:1 theoretical FA release per mole SMG) and DMDM (2:1) and 60% for DAU (4:1) at concentrations of 100uM or less. In time dependent studies over 24 hours, detected FA levels dipped by ca. 10% at 4 hours, returning to initial levels at 24 hours.
Concentration (dilution factor) was found to be the most important parameter governing the percent of FA released consistent with prior literature. This parameter reflects the potential that each compound has as a “delivery depot” for potential cross-linking effects since millimolar concentrations of FARs can be applied safely to ocular tissues.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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