Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation
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 formula...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Drug Delivery |
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| Online Access: | http://dx.doi.org/10.1080/10717544.2021.2021323 |
| _version_ | 1819279585685012480 |
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| author | Yu Ma Jingjing Yang Yali Zhang Chunyan Zheng Zhen Liang Ping Lu Fei Song Yuwei Wang Junjie Zhang |
| author_facet | Yu Ma Jingjing Yang Yali Zhang Chunyan Zheng Zhen Liang Ping Lu Fei Song Yuwei Wang Junjie Zhang |
| author_sort | Yu Ma |
| collection | DOAJ |
| description | 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. |
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| id | doaj.art-3e81670d41344469a14aac3f6a393b83 |
| institution | Directory Open Access Journal |
| issn | 1071-7544 1521-0464 |
| language | English |
| last_indexed | 2024-12-24T00:30:15Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj.art-3e81670d41344469a14aac3f6a393b832022-12-21T17:24:17ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642022-12-0129111112710.1080/10717544.2021.20213232021323Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluationYu Ma0Jingjing Yang1Yali Zhang2Chunyan Zheng3Zhen Liang4Ping Lu5Fei Song6Yuwei Wang7Junjie Zhang8Henan University of Chinese MedicineHenan Eye Institute, Henan Eye Hospital, Zhengzhou University People’s HospitalHenan University of Chinese MedicineThe First Affiliated Hospital of Henan University of Chinese MedicineHenan Eye Institute, Henan Eye Hospital, Zhengzhou University People’s HospitalHenan Eye Institute, Henan Eye Hospital, Zhengzhou University People’s HospitalHenan Eye Institute, Henan Eye Hospital, Zhengzhou University People’s HospitalHenan University of Chinese MedicineHenan Eye Institute, Henan Eye Hospital, Zhengzhou University People’s HospitalNaringenin, 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.http://dx.doi.org/10.1080/10717544.2021.2021323naringeninmicroemulsionsocular drug deliverypharmacokineticscorneal neovascularization |
| spellingShingle | Yu Ma Jingjing Yang Yali Zhang Chunyan Zheng Zhen Liang Ping Lu Fei Song Yuwei Wang Junjie Zhang Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation Drug Delivery naringenin microemulsions ocular drug delivery pharmacokinetics corneal neovascularization |
| title | Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation |
| title_full | Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation |
| title_fullStr | Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation |
| title_full_unstemmed | Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation |
| title_short | Development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization: in vitro and in vivo evaluation |
| title_sort | development of a naringenin microemulsion as a prospective ophthalmic delivery system for the treatment of corneal neovascularization in vitro and in vivo evaluation |
| topic | naringenin microemulsions ocular drug delivery pharmacokinetics corneal neovascularization |
| url | http://dx.doi.org/10.1080/10717544.2021.2021323 |
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