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Journal of Biomaterials Science, Polymer Edition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/tbsp20

Extended elution of phospholipid from silicone hydrogel contact lenses a

a

a

a

William G. Pitt , Yibei Zhao , Daniel R. Jack , Krystian X. Perez , a

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Peter W. Jones , Ryan Marelli , Jared L. Nelson & John D. Pruitt

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Chemical Engineering Department, Brigham Young University, 350 Clyde Bldg, Provo, UT 84602, USA b

Alcon Vision Care, Research and Development, Duluth, GA 30097, USA Published online: 02 Jan 2015.

Click for updates To cite this article: William G. Pitt, Yibei Zhao, Daniel R. Jack, Krystian X. Perez, Peter W. Jones, Ryan Marelli, Jared L. Nelson & John D. Pruitt (2015) Extended elution of phospholipid from silicone hydrogel contact lenses, Journal of Biomaterials Science, Polymer Edition, 26:4, 224-234, DOI: 10.1080/09205063.2014.994947 To link to this article: http://dx.doi.org/10.1080/09205063.2014.994947

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Journal of Biomaterials Science, Polymer Edition, 2015 Vol. 26, No. 4, 224–234, http://dx.doi.org/10.1080/09205063.2014.994947

Extended elution of phospholipid from silicone hydrogel contact lenses William G. Pitta*, Yibei Zhaoa, Daniel R. Jacka, Krystian X. Pereza, Peter W. Jonesa, Ryan Marellia, Jared L. Nelsonb and John D. Pruittb a

Chemical Engineering Department, Brigham Young University, 350 Clyde Bldg, Provo, UT 84602, USA; bAlcon Vision Care, Research and Development, Duluth, GA 30097, USA

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(Received 25 August 2014; accepted 26 November 2014) Characterization of phospholipid release from an experimental reusable wear silicone hydrogel contact lens was performed to assess the possible use of these lenses for phospholipid delivery to increase eye comfort to patients who prefer reusable wear lenses. Contact lenses were loaded with 200 μg of radio-labeled 1,2-dimyristoyl-snglycero-3-phosphocholine (DMPC) from a solution of n-propanol. To simulate 30 days of diurnal use with overnight cleaning, these lenses were eluted for 16 h at 35 °C into artificial tear fluid (ATF), and then eluted at room temperature (~22 °C) for 8 h in one of three commercial contact lens cleaning systems. This was repeated for 30 days. The elution of DMPC into ATF was greater on the first day, followed by a fairly constant amount of elution each day thereafter. The type of cleaning system had a statistically significant effect on the elution rate during daily exposure to ATF. The rate of elution into cleaning solutions did not show any enhanced elution on the first day; there was a fairly constant elution rate. Again, the type of cleaning system significantly influenced the elution rate into the nightly cleaner. Keywords: silicone hydrogel contact lens; diurnal wear; phospholipid delivery; artificial tear fluid; elution; lens cleaning systems

1. Introduction The overarching goal of contact lens manufacturers is to provide a corrective lens that is ophthalmically compatible and comfortable for the user. Some users of reusable lenses desire to wear the lens continuously (overnight) for extended periods of time, and the recent advent of silicone hydrogels with high oxygen and ion permeability has allowed approval of lenses indicated for 6 or 30 days of continuous wear. Most eye care practitioners, however, still recommend daily wear of reusable lenses with nightly removal for cleaning with lens care disinfecting solution. Despite the development of ophthalmically compatible lenses, some users may still experience discomfort, which in some cases might be related to dry eye irritation; this latter irritation sometimes is attributed to the lack of phospholipid in the tear film.[1,2] There are commercial eye drop products designed to relieve eye irritation by supplementing phospholipids to the tears,[3,4] but supplemental drops are often inconvenient to the user. Another approach would be to deliver the phospholipid from a contact lens.

*Corresponding author. Email: [email protected] © 2014 Taylor & Francis

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Supplemental phospholipid is thought to stabilize the tear film, reducing tear film breakup and associated eye irritation.[1,5] Previously, our research group has examined the incorporation of 1,2-dimyristoylsn-glycero-3-phosphocholine (DMPC) in an experimental single-use silicone hydrogel contact lens.[6,7] We have shown that the lenses can be easily loaded and that delivery of the DMPC to artificial tears in vitro is apparently governed by diffusion of phospholipids from the lens. Those previous studies only examined 72 h of delivery in lenses that were designed for single-use wear. About 1 μg of DMPC was delivered from those lenses during the first 10 h of exposure to an artificial tear fluid. Thus, a further objective in our research is to determine if a similar release of DMPC can be accomplished for a reusable lens, or for a ‘planned replacement’ lens on a 30-day replacement cycle. In particular, the question was if the release could be sustained for up to 30 days. Obviously, the lens would need to be loaded with more DMPC, and thus a corollary question arises of whether the visual clarity would be compromised in a lens loaded sufficiently high to provide 30 days of sustained phospholipid release. 2. Procedures 2.1. Lenses Experimental lenses in distilled water in blister packs were obtained from CIBA VISION (Duluth, GA). These lenses were of a delefilcon composition, were designed to be evaluated as 30-day planned replacement lenses, and were designated as experimental lenses only. 2.2.

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Radio-labeled DMPC from New England Nuclear (Waltham, MA) was combined with nonlabeled DMPC (Lipoid, Ludwigshafen, Germany) and dissolved in n-propanol (Mallinckrodt, Phillipsburg, NJ) at a concentration of 9 mg DMPC per mL (0.9% w/v). 2.3. Loading Lenses were removed from blister packs, blotted dry on tissue paper, and loaded with DMPC by soaking for 70, 110, 130, and 150 s in 0.9% (w/v) solution of DMPC in n-propanol at room temperature following the same procedure as detailed previously.[6] This DMPC solution had a 14C activity of 1.4 μCi/mL. During exposure to n-propanol, the lenses swelled and absorbed the DMPC solution. At the designated time, the lens was transferred to distilled water for 5 s, which caused immediate deswelling of the lens and entrapment of the DMPC within the lens. The lens was transferred to a new beaker of distilled water for at least 5 s, and then stored in fresh distilled water until use. The rate of elution of DMPC from the lens into distilled water is extremely slow.[6] These lenses were extracted with n-propanol as described previously to obtain the amount of DMPC loaded.[6] Initial experiments indicated that exposure for 85 s would load the target value of 200 μg DMPC per lens. Subsequently, the lenses were loaded with DMPC by exposure for 85 s to a solution of 0.9% (w/v) solution of DMPC in n-propanol at room temperature (22 °C). Following loading, the lenses were rinsed twice in distilled deionized water (ddH2O) and stored in ddH2O for less than 20 min before the subsequent elution commenced.

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2.4. Elution The lenses were eluted in a simulation of 16 h of wear followed by 8 h of nightly cleaning for 30 sequential days. The lenses were placed in individual 5 mL-capped vials containing 3 mL of artificial tear fluid (ATF) solution at 35 °C. They were shaken on a rotary shaker for 16 h at 60 rpm. The ATF with phospholipids was kindly provided by CIBA VISION and stored at −20 °C until use. The composition of ATF was identical to that used in previous studies of DMPC loading and elution, and is given in Table 1. It contains lactoferrin, lysozyme, lipocalin, and minor lipid components in a PBS buffer. The solution was sampled for eluted DMPC at the end of each 16 h period by collecting 100 μL of ATF from the capped vial. At that same time, each lens was rinsed and transferred to one of three cleaning solutions for 8 h at room temperature, without shaking. The solutions were ReNu® (ReNu® MultiPlus® Multi-Purpose Solution, Bausch & Lomb, Rochester NY), RepleniSH® (OPTI-FREE® RepleniSH® Multi-Purpose Disinfecting Solution with TEARGLYDE®, Alcon Laboratories, Inc., Fort Worth, TX), and Clear Care® (CIBA VISION, Duluth GA). When using the hydrogen peroxide-based cleaning system (Clear Care®), two lenses were placed in one container and the peroxide solution was activated as per the manufacturers’ instructions. A 100 μL sample was collected from each cleaning solution at the end of each 8 h period. At least four lens replicates were done in each cleaning system. The samples collected from the lenses were analyzed by scintillation counting to determine the concentration of DMPC, as has been described previously.[6,7] Briefly, the 100 μL sample was mixed with 10 mL of scintillation fluid in a clear glass scintillation vial, and the scintillation counts were recorded with a Beckman Coulter LS6500 scintillation counter for 1 min. Background counts were subtracted. Standards were made from known concentration of DMPC in n-propanol mixed with 10 mL of scintillation fluid with 100 μL of water. 2.5. Clarity The clarity of the lenses was quantified as the light transmission at 610 nm. Two matching cuvettes containing phosphate buffered saline (PBS) were placed in both the Table 1.

Artificial tear fluid composition.

Component

(mg/mL)

Sodium chloride Sodium phosphatea Sodium dihydrogen phosphatea Lactoferrin Lysozyme Lipocalin (TSP)/β-lactoglobulin Mucin Albumin Cholesterol oleate (esters) Cholesterolb Phosphatidylcholine Phosphatidylethanolamine

8.0 2.128 0.285 2.3 2.2 1.5 0.1 0.0286 0.0186 0.00175 0.0011 0.0005

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The pH was adjusted to 7.5. The cholesterol was complexed with β-cyclodextrin to increase the solubility of cholesterol in the aqueous solution. The concentration above is for the cholesterol portion. b

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sample and reference positions of a UV–Vis spectrophotometer. After the instrument was zeroed, the sample lens was placed in the cuvette in the sample position, ensuring consistent placement and orientation of the lens within the cuvette. The percent transmission was recorded. 2.6. Statistical analysis Data were analyzed using Student-t comparison of means with unequal variances and paired comparisons, applying statistical significance at the 0.05 level. 3. Results Exposure of these lenses to 0.9% (w/v) DMPC solution in n-propanol for 85 s loaded 200.6 ± 1 μg (mean and standard error) per lens. This is a much greater loading than previous research in which different silicone hydrogel lenses were loaded from 23–55 μg per lens from an n-propanol solution.[6,7] As shown in (Figure 1), the amount loaded appears to be fairly linear with exposure time (R2 = 0.981), but extrapolation of this line indicates that the intercept does not pass through zero. Although the loading solution is six times greater than in prior research (0.9% compared with 0.15%), the amount loaded is less than sixfold greater for the same loading time as in the previous studies. This might be attributed to the fact that these experimental lenses are reported to have a different chemistry (designed for reusable wear) than the lenses of the previous study. There was no visible change in clarity following loading. The transmission at 610 nm did not change upon loading of 200 μg (data not shown). 300

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Figure 1. Mass of DMPC loaded per contact lens from 0.9% DMPC in n-propanol as a function of the loading time.

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We exposed each lens to ATF at 35 °C with shaking for 16 h each day, with 8 h of exposure to a cleaning system between ATF exposures. The amount eluted into ATF per day (16 h period) is shown in Figure 2. On day 1, there was significantly more elution into the ATF than subsequent days, releasing about 9.5 μg/lens. As expected, there was no statistically significant difference (p > 0.05) in elution between the various lens groups, probably because these lenses had not yet been exposed to any cleaning solution. However, after the first day, the elutions were smaller and appeared to be a function of the cleaning system. On days 2 through 15, the lenses in the ReNu, RepleniSH®, and Clear Care® cleaning groups, had 16 h ATF elution means of 1.98, 3.58, and 2.36 μg/lens, respectively. On days 16 through 30, these 16 h average elution rates slowed to 1.40, 2.42, and 1.57 μg/lens, respectively. Note that the elution in ATF of those lenses cleaned in RepleniSH was nearly twice as high as lenses cleaned in the other cleaners. Lenses cleaned in ReNu showed a nearly constant elution rate from 16 to 30 days (p > 0.05, test of slope not equal to zero), while the lenses cleaned in RepleniSH and Clear Care systems showed a slightly decreasing elution rate (p < 0.0005, test of slope not equal to zero). 3.3. Elution in cleaning solutions Figure 3 presents the data for elution of the lenses into each of the three cleaning systems during the 8 h of cleaning. There appears to be no excessive release on the first day for any of the systems, but this is not unexpected because these lenses had already been eluted in ATF for 16 h. The ReNu® and Clear Care® solutions produced very low amounts of elution. The average and standard deviation elution in ReNu® over days 1–30 is 0.053 ± 0.031 μg/lens (mean ± SD, 8 h per day). The Clear Care® lens group showed slightly less elution with an average and standard deviation over the 30 days of 0.031 ± 0.016 μg/lens. This is less than one-fourth of the elution in 12 10

µg of DMPC Eluted

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3.2. Elution in ATF

Ave ReNu 8

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Figure 2. Mean mass of DMPC eluted per 16 h period in ATF. Red squares represent the lenses cleaned in ReNu®. Blue triangles represent the lenses cleaned in RepleniSH®. Green diamonds represent the lenses cleaned in Clear Care®. Error bars indicate the standard deviation (n = 4). (Please see the online article for the colour version of this figure: http://dx.doi.org/10.1080/ 09205063.2014.994947.)

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µg of DMPC Eluted

1 Ave ReNu

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Ave RepleniSH Ave Clear Care

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Figure 3. Mean mass of DMPC eluted per 8 h period in a cleaning solution. Red squares represent the lenses cleaned in ReNu®. Blue triangles represent the lenses cleaned in RepleniSH®. Green diamonds represent the lenses cleaned in Clear Care®. Error bars indicate the standard deviation (n = 4). (Please see the online article for the colour version of this figure: http://dx.doi. org/10.1080/09205063.2014.994947.)

ATF. The RepleniSH® showed much more elution with an average and standard deviation over days 1–30 of 0.365 ± 0.195 μg/lens. Interestingly, the elution rate in RepleniSH® was 7 to 10 times greater than the elution rates in ReNu® and Clear Care®. Lenses cleaned in ReNu® and Clear Care® showed a fairly constant elution rate over days 6–30, while lenses cleaned in RepleniSH® displayed decreasing elution during the first 20 days. 120 ReNu

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60 40 20 0

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Figure 4. Average cumulative elution over 30 days. The data incorporate release during elution in ATF and elution in cleaning solution. Red squares represent the lenses cleaned in ReNu®. Blue triangles represent the lenses cleaned in RepleniSH®. Green diamonds represent the lenses cleaned in Clear Care®. Error bars indicate the standard deviation (n = 4). (Please see the online article for the colour version of this figure: http://dx.doi.org/10.1080/09205063.2014.994947.)

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Figure 4 shows the cumulative DMPC elution comprising DMPC released during both the ATF exposure and simulated cleaning periods. Elution from lenses in the RepleniSH® system shows the greatest cumulative elution. The fairly linear increase of the data indicates fairly constant release for all three systems. From day 4 to day 30, the cumulative release from lenses cleaned in RepleniSH® is statistically greater than from lenses cleaned in the other two cleaners. Regarding the elution from lenses cleaned in ReNu® and Clear Care®, there is no statistically significant difference in cumulative release from lenses treated in these two systems at any single day, even at the last day (p > 0.05, single comparison on any day, n ≥ 4). However, a day-by-day paired comparison over the entire 30-day period indicates that elution from lenses cleaned in Clear Care® is greater than from lenses cleaned in ReNu® (p < 0.0001, paired comparison, n = 30). Figure 5 shows the cumulative elution of DMPC during the 16 h ATF exposure periods for the 30 days. Lenses cleaned overnight in RepleniSH® had a cumulative daily elution into ATF of 96 ± 6 μg (mean and standard deviation). For ReNu® and Clear Care® solutions, the cumulative elutions into ATF were 57 ± 8 and 67 ± 5, respectively. Nearly half of the 200 μg loaded into the lenses were eluted into the ATF when the lenses were soaked in RepleniSH®. The trends in elution into ATF from the lenses cleaned in the various cleaning systems are similar to the trends shown in the data of (Figure 4). Again, nearly constant release is evident over the 30 days of 16 h elution into ATF. 4. Discussion This study showed that 200 μg of DMPC could be easily loaded into silicone hydrogel contact lenses by a simple incubation at room temperature in an n-propanol solution of the phospholipid. This loading is much higher than reported previously [6,7] and is 120 Ave ReNu

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3.4. Cumulative elution

Ave RepleniSH

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Ave Clear Care

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Figure 5. Average cumulative elution during the 16 h soaking in ATF over 30 days. The data incorporate release during elution in ATF only. Red squares represent the lenses cleaned in ReNu®. Blue triangles represent the lenses cleaned in RepleniSH®. Green diamonds represent the lenses cleaned in Clear Care®. Error bars indicate the standard deviation (n = 4). (Please see the online article for the colour version of this figure: http://dx.doi.org/10.1080/09205063.2014.994947.)

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remarkable in that the lens remained transparent and the optical clarity of the lenses was not compromised. We tried to simulate 30 days of diurnal wear with nightly disinfection and cleaning by exposing the lenses to 16 h of ATF and then 8 h of the cleaning solutions, each of which contained one or more antimicrobial agents. While the simulation of nightly cleaning was done in contact lens cases with appropriate volumes of cleaning solutions, the simulation of daily wear in our experiments is less exact. While inserted in the eye, a contact lens is continually wiped by the eyelid and has a continual slow flow of tears. Other researchers have developed microfluidic apparatuses to mimic ‘on-eye’ conditions with ‘infinite sink’ conditions, because the fluid is continually fresh without any accumulated product.[8,9] Although we used a large volume (3 mL) reservoir for elution into ATF, this was not an infinite sink with zero DMPC concentration, so the present experiments may have underestimated the elution into ATF by a few percent. The results of our experiments indicated that the elutions during both the wearing and cleaning periods were a function of the cleaning system used. A statistical evaluation indicated that RepleniSH® was associated with the highest cumulative elution during exposure to the cleaning solution (p < 0.0001), and also the highest elution during the daily exposure to ATF (p < 0.0001). Because higher elution also occurred during ATF exposure, we postulate that some component of the OPTI-FREE® RepleniSH® diffuses into the contact lens and remains present and active during elution in ATF. To further support this conclusion, we note that on the first day of elution into ATF, before any exposure to any cleaning solution, the amount of DMPC eluted from each of the three sets of lenses was not statistically different, as can be seen from (Figure 2). However, on the third day of elution into ATF, after two 8 h exposures to the cleaning solutions, the lenses exposed to RepleniSH® started to distinguish themselves as having greater elution into ATF than lenses cleaned in the other two solutions. This is consistent with our hypothesis that there is something in the RepleniSH® solution that enhances elution, and that it apparently adsorbs or absorbs on the lenses and effectuates an increased elution in ATF even after the lenses are removed from the RepleniSH® solution and rinsed in saline. Components of OPTI-FREE® RepleniSH® that are not found in the other cleaning solutions are sodium citrate, propylene glycol, Tetronic® 1304, nonanoyl ethylenediaminetriacetic acid, polyquaternium-1, and myristamidopropyl dimethylamine. At this time, it is unknown if any of these are responsible for the higher elution rates. Alternatively, it could be that something in ReNu® and Clear Care® reduced the elution rates, but we have more doubt about this alternative hypothesis since the components of Clear Care® have very little in common with those of ReNu®. The components of all the cleaning solutions used herein are listed in Table 2, as taken from the containers and/or their packaging. Previous work in our laboratory showed that DMPC elution is a strong function of the elution solution and that water elutes DMPC poorly, while ATF elutes it much faster.[6] We speculated that faster elution might be due to the solubility of DMPC in the ATF solution. The ATF we used contains several components, including proteins and phospholipids. It might be that there are already micelles, liposomes, or proteins in the ATF solution that can easily sorb DMPC as these structures collide with the contact lens surface. No such colloidal structures exist in pure water, so transport from the lens surface might be slower in water. As for the differences in these cleaning solutions, they all contain various salts and surfactants that might be involved in removing DMPC

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Table 2.

Components of cleaning solutions.

Brand name ®

Components ®

ReNu Multiplus multi-purpose solution OPTI-FREE® RepleniSH® multi-purpose disinfection solution

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Clear Care®

Hydranate® (hydroxyalkylphosphonate), boric acid, edetate sodium, poloxamine, sodium borate, sodium chloride, Dymed® (polyaminopropyl biguanide) 0.0001% Sodium citrate, sodium chloride, sodium borate, propylene glycol, TEARGLYDE® (Tetronic® 1304, nonanoyl ethylenediaminetriacetic acid), POLYQUAD® (polyquaternium-1) 0.001%, ALDOX® (myristamidopropyl dimethylamine) 0.0005% Hydrogen peroxide, sodium chloride, phosphonic acid, phosphate buffer, Pluronic® 17R4

from the lens surface into solution. Perhaps more of this surface-collision transport occurs with RepleniSH® than with the other two cleaners. As mentioned, an alternative hypothesis is that some component of RepleniSH® is diffusing into the contact lens and interacting with the polymer itself to reduce the resistance of DMPC transport out of the lens. To date, we have no solid evidence for either hypothesis, but we are considering experiments to examine these phenomena in more detail. With respect to a practical application of this technology in a possible commercial contact lens, the most significant observation is that the rate of elution from DMPC does not dwindle to nothing after few days, but continues at a fairly constant rate for at least 30 days. Depending on the cleaning solution used, up to 110 μg of the 200 μg available was eluted at a fairly constant rate following the burst on the first day. Even with ReNu®, nearly 60 μg (30% of the available DMPC) was released in 30 days. Previously, we reported that a different experimental lens eluted about 0.92 μg in the first 10 h of exposure to ATF, or an average of 0.09 μg/h. For the experimental lenses in this study, on the first day, 9.56 μg of DMPC eluted in 16 h. For comparison, this is about 0.6 μg per hour, a much higher rate than reported in the previous study. It should be noted that the lenses in this study had sixfold more DMPC (200 μg instead of 33 μg) than the lenses in the previous study, and on the first day of this study, the elution exhibited some kind of burst effect. The average elution into ATF over the entire study was 0.20 μg/h for lenses exposed to RepleniSH® (30 days, 16 h/day), 0.14 μg/h for lenses exposed to Clear Care®, and 0.12 μg/h for lenses exposed to ReNu. Compared with the previous study, these are fairly high average release rates, but one should always consider that the loading is higher and the lens material is different. A benchmark comparison is the average rate of natural phosphatidylcholine production into ocular tears. The normal physiological tear production volumetric rate ranges from 0.5 to 2.2 μL/min, with an average of 1.2 μL/min.[10] The concentration of phosphatidylcholines in tears is about 1.1 μg/mL.[11] A calculation using these averages indicates that the average rate of natural phosphatidylcholine production into ocular tears is about 0.08 μg/h. Thus, a lens loaded with 200 μg can apparently deliver more than the average amount of normal phosphatidylcholine production. Lenses of lower DMPC loading might be adequate for a comfort application if supplemental phospholipids are indicated.

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These experiments simulated a planned replacement diurnal use of a lens for 30 days with 16 h of wear and 8 h of cleaning. But we expect that similar amounts of DMPC would be eluted during continuous wear for 20 days (without nightly removal). We say ‘similar’ in a very general sense. The study showed that the cleaning solution makes a difference, but we do not know if the cleaning increases or decreases the rate of elution into ATF compared with if no cleaning protocol was used. The data of the elution from the first day (prior to exposure to cleaner) cannot be extrapolated to 30 days, because it is probably confounded by a burst effect that apparently was completed within 16 h. The other consideration for 20 days of continuous wear is that the rate may slow down with time more than shown in this study, because in this study, the 8 h of exposure to a cleaning solution may have allowed time for the redistribution of DMPC within the lens. For example, toward the end of the 16 h of rapid elution into ATF, the DMPC concentration at the lens surface may have been depleted compared with the concentration deeper in the lens. But during the 8 h of much slower elution into cleaning solution, the DMPC may have diffused within the lens to replenish the DMPC at the lens surface. This hypothesis is the basis of one scenario as to why the elution rate was fairly constant over 30 days during which time, the total DMPC in the lens was depleted by one-third to half of the original loading. This hypothesis remains to be tested. For clinical applications, the question also remains as to whether the amount of phospholipid release exemplified in this report is sufficient to provide any comfort effect, which can only be answered by clinical trials. Disclosure statement There are no conflicts of interest. The authors derive no financial interest or benefit from the applications of this research.

Funding This work was supported by funding from Alcon Vision Care, Research and Development, and the Pope Professorship of Brigham Young University.

References [1] Peters K, Millar TJ. The role of different phospholipids on tear break-up time using a model eye. Curr. Eye Res. Jul 2002;25:55–60. [2] Korb DR, Greiner JV, Glonek T. Tear film lipid layer formation: implications for contact lens wear. Optometry Vision Sci. 1996;73:189–192. [3] McCann LC, Tomlinson A, Pearce EI, Papa V. Effectiveness of artificial tears in the management of evaporative dry eye. Cornea. Jan 2012;31:1–5. [4] Benelli U. Systane lubricant eye drops in the management of ocular dryness. Clin. Ophthalmol. 2011;5:783–790. [5] Blackie CA, Solomon JD, Scaffidi RC, Greiner JV, Lemp MA, Korb DR. The relationship between dry eye symptoms and lipid layer thickness. Cornea. Aug 2009;28:789–794. [6] Pitt WG, Jack DR, Zhao Y, Nelson JL, Pruitt JD. Loading and release of DMPC from contact lenses. Optometry Vision Sci. 2011;88:502–506. [7] Pitt WG, Jack DR, Zhao YZ, Nelson JL, Pruitt JD. Transport of phospholipid in silicone hydrogel contact lenses. J. Biomater. Sci., Polym. Ed. 2012;23:527–541.

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[8] Ali M, Horikawa S, Venkatesh S, Saha J, Hong JW, Byrne ME. Zero-order therapeutic release from imprinted hydrogel contact lenses within in vitro physiological ocular tear flow. J. Controlled Release. 2007;124:154–162. [9] White CJ, McBride MK, Pate KM, Tieppo A, Byrne ME. Extended release of high molecular weight hydroxypropyl methylcellulose from molecularly imprinted, extended wear silicone hydrogel contact lenses. Biomaterials. Aug 2011;32:5698–5705. [10] Mishima S, Gasset A, Klyce SD Jr, Baum JL. Determination of tear volume and tear flow. Invest. Ophthalmol. Jun 1966;5:264–276. [11] McCulley JP, Shine WE. Eyelid disorders: the meibomian gland, blepharitis, and contact lenses. Eye Contact Lens. Jan 2003;29:S93–5; discussion S115-8, S192-4.

Extended elution of phospholipid from silicone hydrogel contact lenses.

Characterization of phospholipid release from an experimental reusable wear silicone hydrogel contact lens was performed to assess the possible use of...
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