AUTHOR=Shi Jieran , Yang Jingjing , Xu Haohang , Luo Qing , Sun Jun , Zhang Yali , Liang Zhen , Zhao Ningmin , Zhang Junjie 

TITLE=Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1157084

DOI=10.3389/fphar.2023.1157084

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Corneal neovascularization (CNV) is a pathological condition that can disrupt corneal transparency, thus harming visual acuity. However, there is no effective drug to treat CNV. Sunitinib (STB), a small-molecule multiple receptor tyrosine kinase inhibitor, was shown to have an effect on CNV. The purpose of this study was to develop an STB microemulsion (STB-ME) eye drop to inhibit CNV by topical application.</p><p><bold>Methods:</bold> We successfully prepared an STB-ME by the phase inversion emulsification method, and the physicochemical properties of STB-MEs were investigated. The short-term storage stability, cytotoxicity to human corneal epithelial cells, drug release, ocular irritation, ocular pharmacokinetics and the inhibitory effect on CNV were evaluated <italic>in vitro</italic> and <italic>in vivo</italic>.</p><p><bold>Results:</bold> The optimal formulation of STB-ME is composed of oleic acid, CRH 40, Transcutol P, water and sodium hyaluronate (SH). It is a uniform spherical particle with a mean droplet size of 18.74 ± 0.09 nm and a polydispersity index of 0.196 ± 0.004. In the <italic>in vitro</italic> drug release results, STB-ME showed sustained release and was best fitted by a Korsmeyer-Peppas model (<italic>R</italic><sup><italic>2</italic></sup> = 0.9960). The results of the ocular pharmacokinetics in rabbits showed that the formulation containing SH increased the bioavailability in the cornea (2.47-fold) and conjunctiva (2.14-fold). STB-ME (0.05% and 0.1%), administered topically, suppressed alkali burn-induced CNV in mice more effectively than saline, and high-dose (0.1%) STB-ME had similar efficacy to dexamethasone (0.025%).</p><p><bold>Conclusion:</bold> This study provides a promising formulation of STB-ME for the inhibition of CNV by topical administration, which has the excellent characteristics of effectiveness, sustained release and high ocular bioavailability.</p>