Quercetin loaded biogenic squalene nano-lipid carriers for the treatment of dry eye syndrome

Abstract

In this study, quercetin-incorporated squalene nanostructured lipid carriers (QS-NLCs) were developed to mitigate the pathological conditions of dry eye disease (DED). The melt emulsification method was used to prepare QS-NLCs. The resulting NLCs have 93.74 ± 9.32 nm particle size, 43.8 ± 5.42 % drug loading and showed good stability for 90 days at different storage conditions. The structural characterization of NLCs was carried out through DSC, FTIR, and XRD, and the morphological study was conducted using TEM analysis. The morphological study emphasised no agglomeration was present in the formulation, and further -31.47 ± 2.18 mV zeta potential supported the TEM analysis. Also, the QS-NLCs showed a release pattern in which more than 70 % of the drug was released in the medium in 1 h. After that, a sustained release pattern was observed for 6 h. However, QS-NLCs also showed higher ex-vivo corneal permeation, i.e., ∼2.5-fold, as compared to free quercetin. Also, no significant difference was observed in the moisture retention capacity of NLCs when compared with control glycerin. Further, the QS-NLCs showed good anti-inflammatory and cytotoxicity activities against RAW 264.7 and HCECs cell lines, respectively. Furthermore, 18.22 ± 1.23 mm of Schirmer score in a 5-day tear production study and a 2.79-fold increased half-life (T1/2), 3.02-fold enhanced area under the curve (AUC0-∞), and 2.88-fold higher mean retention time (MRT0-∞) were obtained which signified the higher bioavailability of QS-NLCs with higher ocular tolerance ensured by modified Draize test. Most importantly, the proposed QS-NLCs improved the pharmacological activities of quercetin against DED.

Keywords: Anti-inflammatory; NLCs; Ocular pharmacokinetic; Quercetin; Squalene.