Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo
Background: 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...
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| Format: | Article |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1157084/full |
| _version_ | 1797783487198003200 |
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| author | Jieran Shi Jingjing Yang Haohang Xu Qing Luo Jun Sun Yali Zhang Zhen Liang Ningmin Zhao Junjie Zhang |
| author_facet | Jieran Shi Jingjing Yang Haohang Xu Qing Luo Jun Sun Yali Zhang Zhen Liang Ningmin Zhao Junjie Zhang |
| author_sort | Jieran Shi |
| collection | DOAJ |
| description | Background: 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.Methods: 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 in vitro and in vivo.Results: 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 in vitro drug release results, STB-ME showed sustained release and was best fitted by a Korsmeyer-Peppas model (R2 = 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%).Conclusion: 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. |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T00:26:38Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-f5443a8013c6428bb285f400b352a8f92023-07-11T05:05:43ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-07-011410.3389/fphar.2023.11570841157084Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivoJieran Shi0Jingjing Yang1Haohang Xu2Qing Luo3Jun Sun4Yali Zhang5Zhen Liang6Ningmin Zhao7Junjie Zhang8Department of Pharmacy, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaDepartment of Pharmacy, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Pharmacy, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Pharmacy, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaFirst School of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, ChinaHenan Eye Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaDepartment of Pharmacy, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaBackground: 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.Methods: 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 in vitro and in vivo.Results: 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 in vitro drug release results, STB-ME showed sustained release and was best fitted by a Korsmeyer-Peppas model (R2 = 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%).Conclusion: 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.https://www.frontiersin.org/articles/10.3389/fphar.2023.1157084/fullSunitinibmicroemulsionocular deliverytopical administrationcorneal neovascularizationocular pharmacokinetics |
| spellingShingle | Jieran Shi Jingjing Yang Haohang Xu Qing Luo Jun Sun Yali Zhang Zhen Liang Ningmin Zhao Junjie Zhang Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo Frontiers in Pharmacology Sunitinib microemulsion ocular delivery topical administration corneal neovascularization ocular pharmacokinetics |
| title | Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo |
| title_full | Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo |
| title_fullStr | Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo |
| title_full_unstemmed | Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo |
| title_short | Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo |
| title_sort | preparation of a sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo |
| topic | Sunitinib microemulsion ocular delivery topical administration corneal neovascularization ocular pharmacokinetics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1157084/full |
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