Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation
The application of ketoconazole (KET) in ocular drug delivery is restricted by its poor aqueous solubility though its broad-spectrum antifungal activity. The aim of this study is to develop an ion-sensitive in situ gel (ISG) of KET to promote its ocular bioavailability in topical application. The so...
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| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2024.2424217 |
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| author | Huiyun Xia Jingjing Yang Fei Song Guojuan Pu Fudan Dong Zhen Liang Junjie Zhang |
| author_facet | Huiyun Xia Jingjing Yang Fei Song Guojuan Pu Fudan Dong Zhen Liang Junjie Zhang |
| author_sort | Huiyun Xia |
| collection | DOAJ |
| description | The application of ketoconazole (KET) in ocular drug delivery is restricted by its poor aqueous solubility though its broad-spectrum antifungal activity. The aim of this study is to develop an ion-sensitive in situ gel (ISG) of KET to promote its ocular bioavailability in topical application. The solubility of KET in water was increased by complexation with hydroxypropyl-β-cyclodextrin (HPβCD), then KET-HPβCD inclusion complex (KET-IC) was fabricated into an ion-sensitive ISG triggered by sodium alginate (SA). The in vitro drug release and antifungal activities investigations demonstrated that the KET-IC-ISG formulation increased drug release and anti-fungal activities compared to pure KET. The ex vivo rabbit corneal permeation studied demonstrated higher permeability of KET-IC-ISG formulation (Papp of (6.34 [Formula: see text]0.21) [Formula: see text]10−4 cm/h) than pure KET (Papp of (3.09 [Formula: see text] 0.09) [Formula: see text]10−4 cm/h). The cytotoxicity assay and the ocular irritation study in rabbits confirmed the KET-IC-ISG safety and well tolerance. The ocular pharmacokinetics of KET in rabbits was investigated and the results showed that the KET-IC-ISG increased its bioavailability in cornea by 47-fold. In conclusion, the KET-IC-ISG system promoted the precorneal retention, the ocular drug bioavailability and the developed formulation is a potential strategy to treat mycotic keratitis. |
| format | Article |
| id | doaj-art-a6661559ca6046229fb77cb264057066 |
| institution | DOAJ |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-a6661559ca6046229fb77cb2640570662025-08-20T03:22:00ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642024-12-0131110.1080/10717544.2024.2424217Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluationHuiyun Xia0Jingjing Yang1Fei Song2Guojuan Pu3Fudan Dong4Zhen Liang5Junjie Zhang6Henan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaHenan Eye Hospital, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, ChinaThe application of ketoconazole (KET) in ocular drug delivery is restricted by its poor aqueous solubility though its broad-spectrum antifungal activity. The aim of this study is to develop an ion-sensitive in situ gel (ISG) of KET to promote its ocular bioavailability in topical application. The solubility of KET in water was increased by complexation with hydroxypropyl-β-cyclodextrin (HPβCD), then KET-HPβCD inclusion complex (KET-IC) was fabricated into an ion-sensitive ISG triggered by sodium alginate (SA). The in vitro drug release and antifungal activities investigations demonstrated that the KET-IC-ISG formulation increased drug release and anti-fungal activities compared to pure KET. The ex vivo rabbit corneal permeation studied demonstrated higher permeability of KET-IC-ISG formulation (Papp of (6.34 [Formula: see text]0.21) [Formula: see text]10−4 cm/h) than pure KET (Papp of (3.09 [Formula: see text] 0.09) [Formula: see text]10−4 cm/h). The cytotoxicity assay and the ocular irritation study in rabbits confirmed the KET-IC-ISG safety and well tolerance. The ocular pharmacokinetics of KET in rabbits was investigated and the results showed that the KET-IC-ISG increased its bioavailability in cornea by 47-fold. In conclusion, the KET-IC-ISG system promoted the precorneal retention, the ocular drug bioavailability and the developed formulation is a potential strategy to treat mycotic keratitis.https://www.tandfonline.com/doi/10.1080/10717544.2024.2424217Ketoconazoleion-sensitive in situ gelfungal keratitisocular drug deliveryocular pharmacokinetics |
| spellingShingle | Huiyun Xia Jingjing Yang Fei Song Guojuan Pu Fudan Dong Zhen Liang Junjie Zhang Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation Drug Delivery Ketoconazole ion-sensitive in situ gel fungal keratitis ocular drug delivery ocular pharmacokinetics |
| title | Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation |
| title_full | Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation |
| title_fullStr | Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation |
| title_full_unstemmed | Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation |
| title_short | Development of ion-triggered in situ gel containing ketoconazole/hydroxypropyl-β-cyclodextrin for ocular delivery: in vitro and in vivo evaluation |
| title_sort | development of ion triggered in situ gel containing ketoconazole hydroxypropyl β cyclodextrin for ocular delivery in vitro and in vivo evaluation |
| topic | Ketoconazole ion-sensitive in situ gel fungal keratitis ocular drug delivery ocular pharmacokinetics |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2024.2424217 |
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