Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization

Abstract

Isoliquiritigenin (ISL), as a natural flavonoid, has been proven to have therapeutic potential for corneal neovascularization (CNV) treatment; however, its therapeutic use is restricted due to its poor aqueous solubility and limited bioavailability. To overcome these limitations, a novel ISL-loaded nanoemulsion (ISL-NE) was designed for inhibiting CNV in this study. ISL-NE formulation was composed of propylene glycol dicaprylate (PGD), Cremophor® EL (EL35), polyethylene glycol 400 (PEG 400) and adding water with sodium hyaluronate, its particle size was 34.56 ± 0.80 nm with a low polydispersity index of less than 0.05, which suggested a narrow size distribution. The results demonstrated that ISL-NE released higher and permeated more drug than ISL suspension (ISL-Susp) in in vitro drug release and ex vivo corneal permeation study. ISL-NE showed no cytotoxicity in human corneal epithelial cells toxicity study, which was consistent with the result of ocular irritation study in rabbit eyes. ISL-NE had bioavailability 5.76-fold, 7.80-fold and 2.13-fold higher than ISL-Sups in tears, cornea and aqueous humor after a single dose of ISL-NE, respectively. Furthermore, the efficacy of ISL-NE treatment (0.2% ISL) was comparable to that of dexamethasone treatment (0.025%) in the inhibition of CNV in mice model. Enzyme-linked immunosorbent assay (ELISA) showed that the expressions of corneal vascular endothelial growth factor (VEGF-A) and matrix metalloproteinase (MMP-2) were decreased. In conclusion, the ISL-NE demonstrated excellent physicochemical properties, good tolerance, and enhanced ocular bioavailability. It could be a promising, safe, and effective treatment for CNV.

Formulating Resveratrol and Melatonin Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Ocular Administration Using Design of Experiments

“…These values could be considered optimal for an ophthalmic liquid formulation that should be non-irritating once applied [ 45 ]. Higher or lower values of osmolarity could cause irritation and extensive lachrymation, provoking a rapid wash-out of the solution and consequently a poor drug local bioavailability [ 46 ].…”

Isoliquiritigenin Nanoemulsion Preparation by Combined Sonication and Phase-Inversion Composition Method: In Vitro Anticancer Activities

“…Meanwhile, ILQ demonstrated its highest solubility in Cremophor ® EL (664.33 ± 0.0065 mg g −1 ) among the tested surfactants. Cremophor ® EL creates a strong spatial repulsive force that prevents droplet aggregation and has low toxicity [ 23 ]. In this context, Labrafil ® M 1944 CS was chosen as the oil phase, and Cremophor ® EL was selected as the surfactant.…”

Apremilast Treatment of Cancer in Mice Tumorised with Breast Cancer: In Vivo Study

“…Physiologic levels must be used in pathogenetic research because of the bell-shaped dose-response curve of estrogen (14)(15)(16). We administered Apremilast without stopping the estradiol in order to mimic the clinical scenario in premenopausal women (27).…”

“…Estrogen and apremilast increased VEGF levels (21,28). Estrogen, angiogenesis, metastasis, and antiestrogen treatment all have an effect on breast cancer (26,27,29). More research is required on the hormonal regulation of angiogenic factors and angiogenesis in breast cancer (22)(23)(24).…”