Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation

Abstract

Naringenin, a flavonoid, possesses antiangiogenic potential and inhibits corneal neovascularization (CNV); however, its therapeutic use is restricted due to poor solubility and limited bioavailability. In this study, we developed a naringenin microemulsion (NAR-ME) for inhibiting CNV. NAR-ME formulation was composed of triacetin (oil phase), Cremophor RH40 (CRH40), PEG400, and water, its droplet size was 13.22 ± 0.13 nm with a narrow size distribution (0.112 ± 0.0014). The results demonstrated that NAR-ME released higher and permeated more drug than NAR suspension (NAR-Susp) in in vitro drug release and ex vivo corneal permeation study. Human corneal epithelial cells (HCECs) toxicity study showed no toxicity with NAR-ME, which is consistent with the result of ocular irritation study. NAR-ME had high bioavailability 1.45-fold, 2.15-fold, and 1.35-fold higher than NAR-Susp in the cornea, conjunctiva, and aqueous humor, respectively. Moreover, NAR-ME (0.5% NAR) presented efficacy comparable to that of dexamethasone (0.025%) in the inhibition of CNV in mice CNV model induced by alkali burning, resulting from the attenuation of corneal vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP-14) expression. In conclusion, the optimized NAR-ME formulation demonstrated excellent physicochemical properties and good tolerance, enhanced ocular bioavailability and corneal permeability. This formulation is promising, safe, and effective for the treatment of CNV.

Development of a Luliconazole Nanoemulsion as a Prospective Ophthalmic Delivery System for the Treatment of Fungal Keratitis: In Vitro and In Vivo Evaluation

“…The observed results confirmed that the LCZ-NE could significantly enhance LCZ release compared to the pure drug suspension. The ability of NEs to increase the dissolution of poorly aqueous-soluble drugs has been observed in previous published research [ 43 ]. The in vitro release kinetics of LCZ from the LCZ-NE were analyzed using different mathematical models, with pure LCZ used as a control.…”

“…In order to study the thermodynamic stability of the LCZ-NE, three freeze/thaw rounds were performed on freshly prepared LCZ-NE [ 43 ]. In Brief, the LCZ-NE was added into a transparent glass bottle and sealed, then stored in a refrigerator at −20 for 18 h. After that, the bottle was removed, kept at room temperature (25 ) for 18 h and returned to the refrigerator with the same previous temperature for another 18 h, in order to fulfill the second cycle.…”

Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization, in-vitro, ex-vivo, and in-vivo studies evaluation

“…The drug release from LORA-NLCs formulae was fitted in several mathematical models to identify the mechanism of release. The values of the regression coefficient imply that the Higuchi model was the best fit for the LORA-NLCs release profile (Ma et al, 2022 ).…”

An Update on Novel Ocular Nanosystems with Possible Benefits in the Treatment of Corneal Neovascularization

“…Several plant extracts, including epigallocatechin gallate (EGCG), 42 celastrol, 43 curcumin, 44 kaempferol 45 and naringenin, 46 have been found to inhibit experimental CNV. The plant extracts mentioned above (except EGCG, which is a water-soluble active ingredient) are all hydrophobic molecules.…”

“…Other plant extracts, including celastrol, curcumin, kaempferol and naringenin, are hydrophobic molecules that limit their clinical use. In response, they were encapsulated in micelles, 43 NPs, 44 GNPs 45 and microemulsions 46 respectively to greatly improve their water solubility while still retaining their activities in CNV therapy.…”