Influence of benzalkonium chloride on tear film lipid layer stability: a molecular level view by employing in silico modeling

Benzalkonium chloride (BAK) is a mixture of aliphatic C12 and C14 quaternary ammoniums. These molecules are traditionally used to preserve eye drops because of their bactericidal and bacteriostatic properties. The compounds of BAK have an amphiphilic character, hence it can be assumed that on the ocular surface they can interact and alter the properties of the tear film lipid layer (TFLL). Indeed, BAK was demonstrated to decrease the breakup time in patients, which is a hallmark of TFLL destabilization. The amphiphilic and water-soluble C12 and C14 BAK molecules are expected to act predominantly at the aqueous-lipid interface that, as we have demonstrated earlier, is populated mostly by polar lipids.7,8 Notably, these BAK species are short-chain analogues of cetalkonium chloride (CKC) that, as we have shown previously, interact with the TFLL model, improving its stability. We hypothesize that by influencing polar lipids, BAK (C12 and C14) can alter the details of molecular-level interactions between individual species of TFLL and indirectly influence the macroscopic behavior of the film, in particular its organization and stability.