Biophysical profiling of synthetic ultra-long tear film lipids

Early-Stage Development of an Anti-Evaporative Liposomal Formulation for the Potential Treatment of Dry Eyes

“…On the whole, a sound indication that the mode of action of the lipid species are not affected by the source of their origin or the temperature. While we have in our earlier reports disclosed information on the correlation between film structure and evaporation-resistant properties and shown that films existing in the liquid state do not significantly reduce the evaporation rate of water from the underlying subphase, [24][25][26]34,35 we proceeded by assessing the capabilities of formulation 1 (Figure 2C). As expected, the film formed by formulation 1 did not have a statistically significant effect on the aqueous evaporation rate when compared to the control (aqueous layer without a lipid film covering it).…”

“…26 In more detail, the 20-OAHFA was tailored to maintain the functional characteristics of the average TFLL OAHFA ((21Z)-29-oleoyloxynonacos-21-enoic acid used as a model, i.e., 29:1/18:1-OAHFA, later referred to as 29-OAHFA), that is, to capture its surface-active properties, phase transition behavior, and evaporation-resistant function in an economically more sensible form. 24,25 This would be more appealing from an industrial upscaling perspective as the length of the synthetic routes are considerably shorter than those required to reach the naturally occurring OAHFAs (2−3 steps for 20-OAHFA 24 vs 9−10 steps for 29-OAHFA). 25 BO, on the other hand, is a commercially affordable endogenous TFLL lipid that when applied together with the 20-OAHFA species significantly enhances the evaporation resistance of the formed film.…”

“…24,25 This would be more appealing from an industrial upscaling perspective as the length of the synthetic routes are considerably shorter than those required to reach the naturally occurring OAHFAs (2−3 steps for 20-OAHFA 24 vs 9−10 steps for 29-OAHFA). 25 BO, on the other hand, is a commercially affordable endogenous TFLL lipid that when applied together with the 20-OAHFA species significantly enhances the evaporation resistance of the formed film. We therefore envisioned that incorporation of these species in a treatment for DED would allow replenishment of proper TFLL structure and restoration of its key functions with minimal disruptive effects on the dynamic behavior of this biological membrane.…”

“…Recent work has showcased that out of the many unique lipid classes found in the TFLL, the wax esters (WEs) and O -acyl-ω-hydroxy fatty acids (OAHFAs) hold significant potential from the DED treatment perspective. In more detail, they display the characteristic biophysical profiles required to promote active spreading of lipids at the aqueous interface (tear film stabilizing action) and enhance the evaporation resistance of the formed film (moderation of evaporation rate). , In our most recent work, we identified a promising lipid composition comprising the WE behenyl oleate (BO) and OAHFA 20-oleoyloxy-eicosanoic acid (20:0/18:1-OAHFA, later referred to as 20-OAHFA) which spread efficiently at the aqueous interface to yield a lipid film with excellent evaporation-resistant properties at physiological ocular surface pressure (20–40 mN/m) and temperature (35 °C) . In more detail, the 20-OAHFA was tailored to maintain the functional characteristics of the average TFLL OAHFA ((21 Z )-29-oleoyloxynonacos-21-enoic acid used as a model, i.e., 29:1/18:1-OAHFA, later referred to as 29-OAHFA), that is, to capture its surface-active properties, phase transition behavior, and evaporation-resistant function in an economically more sensible form. , This would be more appealing from an industrial upscaling perspective as the length of the synthetic routes are considerably shorter than those required to reach the naturally occurring OAHFAs (2–3 steps for 20-OAHFA vs 9–10 steps for 29-OAHFA) .…”

Another Brick in the Wall of Tear Film Insights Added Through the Total Synthesis and Biophysical Profiling of anteiso-Branched Wax and Cholesteryl Esters

“…The power of synthetic chemistry can be harnessed to circumvent these shortcomings. Recently, reports on the chemical synthesis and biophysical profiling of several key human tear film species have emerged, including O -acyl-ω-hydroxy fatty acids (OAHFAs), diesters, and n / iso -branched wax and cholesteryl esters (WEs and CEs). − Nevertheless, reports on the total synthesis and biophysical profiling of tear film anteiso -branched WEs and CEs are absent from the literature. Insights on their properties are required to supplement the current knowledge and build an overarching understanding on the effects of chain branching on the structure and function of tear film WEs and CEs.…”