Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation.
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引用次数: 11
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.
期刊介绍:
Drug Delivery is an open access journal serving the academic and industrial communities with peer reviewed coverage of basic research, development, and application principles of drug delivery and targeting at molecular, cellular, and higher levels. Topics covered include all delivery systems including oral, pulmonary, nasal, parenteral and transdermal, and modes of entry such as controlled release systems; microcapsules, liposomes, vesicles, and macromolecular conjugates; antibody targeting; protein/peptide delivery; DNA, oligonucleotide and siRNA delivery. Papers on drug dosage forms and their optimization will not be considered unless they directly relate to the original drug delivery issues. Published articles present original research and critical reviews.