The tear film lipid layer (TFLL) covers the tear film, stabilizing it and providing a protective barrier against the environment. The TFLL is divided into polar and non-polar sublayers, but the interplay between lipid classes in these sublayers and the structure-function relationship of the TFLL remains poorly characterized. This study aims to provide insight into TFLL function by elucidating the interactions between polar and non-polar TFLL lipids at the molecular level. Mixed films of polar O-acyl-ω-hydroxy fatty acids (OAHFA) or phospholipids and non-polar cholesteryl esters (CE) were used as a model of the TFLL. The organization of the films were studied by using a combination of Brewster angle and fluorescence microscopy in a Langmuir trough system. In addition, the evaporation resistance of the lipid films was evaluated. Phospholipids and OAHFAs induced the formation of a stable multilamellar CE film. The formation of this film was driven by the interdigitation of acyl chains between the monolayer of polar lipids and the CE multilayer lamellae. Surprisingly, the multilayer structure was destabilized by both low and high concentrations of polar lipids. In addition, the CE multilayer was no more effective in resisting the evaporation of water than a polar lipid monolayer. Formation of multilamellar films by major tear film lipids suggest that the TFLL may have a similar structure. Moreover, in contrast to the current understanding, polar TFLL lipids may not mainly act by stabilizing the non-polar TFLL sublayer, but through a direct evaporation resistant effect.

Dry eye syndrome (DES) is a prevalent disease in which the tear film homeostasis is compromised. One of the main causes of DES is thought to be an alteration in the composition of the outermost layer of the tear film, the tear film lipid layer (TFLL), resulting in increased evaporation of water from the tear film and subsequent drying of the ocular surface. Recent studies have suggested that the specific TFLL-lipids; O-acyl-ω-hydroxy-fatty acids (OAHFAs) and diesters (DiEs) may play a role in development of DES. However, their specific connection to DES has remained largely unknown until now, due to lack of information on their biophysical properties and their role in the TFLL. In this study, we have addressed this issue by studying the biophysical properties and evaporation resistance of a library containing ten synthetic analogues of TFLL OAHFAs and DiEs. Our results show how variation of chain length and polar groups affect the phase behaviour of these lipids at the tear film surface. In addition, the results revealed that OAHFAs exhibiting a liquid expanded-solid phase transition formed films with high evaporation resistance, while the DiEs were found to have no evaporation resistance. Altogether, our results shed new light on the role of the OAHFAs and DiEs in the TFLL and their connection to DES, suggesting that OAHFAs are likely a key lipid class in maintaining TFLL evaporation resistance.

Soft nanoparticles are interesting materials due to their size, deformability and ability to host quest molecules. Surface properties play an essential role in determining the fate of the particles in biological medium and coating of the nanoparticles (and polymers) with carbohydrates have been found to be an efficient strategy for increasing their biocompatibility and fine-tuning other important properties such as aqueous solubility. In this work, soft nanogels of poly(N-vinylcaprolactam), PNVCL, were surface functionalized with different glucose and maltose ligands and the colloidal properties of the gels were analyzed. The PNVCL nanogels were first prepared via semi-batch precipitation polymerization, where a comonomer, propargyl acrylate (PA) was added after preparticle formation. Aim was to synthesize “clickable” nanogels with alkyne groups on their surfaces. The nanogels were then functionalized with two separate azido-glucosides and azido-maltosides (containing different linkers) through a copper catalyzed azide-alkyne cycloaddition (CuAAc) click reaction. The glucose and maltose bearing nanogels were thermoresponsive and shrank upon heating. Compared to the PNVCL-PA nanogel, the carbohydrate bearing ones were larger, more hydrophilic, had volume phase transitions at higher temperatures and were more stable against salt induced precipitation. In addition to investigating the colloidal properties of the nanogels, the carbohydrate recognition was addressed by studying the interactions with a model lectin, concanavalin A (Con A). The binding efficiency was not affected by the temperature which indicates that the sugar moieties are located on the gel surfaces, and capable of interacting with other biomolecules independent of temperature. Thus the synthesis produces nanogels with surface functions capable of bio-relevant interactions and thermoresponsive structures. The particles should be useful in drug delivery applications.