Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model
The limited bioavailability of orally administered repaglinide presents a significant challenge in diabetes management, which can be addressed by developing a buccoadhesive drug delivery system. In this study, repaglinide-loaded cubosomes were prepared using a top-down approach and optimized via a 3...
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Elsevier
2025-12-01
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| Series: | International Journal of Pharmaceutics: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156725000428 |
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| author | Nihal Farid Younes Randa Latif Alia Badawi Khaled Hegazy |
| author_facet | Nihal Farid Younes Randa Latif Alia Badawi Khaled Hegazy |
| author_sort | Nihal Farid Younes |
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| description | The limited bioavailability of orally administered repaglinide presents a significant challenge in diabetes management, which can be addressed by developing a buccoadhesive drug delivery system. In this study, repaglinide-loaded cubosomes were prepared using a top-down approach and optimized via a 33 Box-Behnken design. The optimized formulation (Opt-RPG-CUB) was characterized for solubilization efficiency (SE%), particle size (PS), zeta potential (ZP), drug release kinetics, and morphology. To further enhance drug delivery, a 22 factorial design was utilized to incorporate varying concentrations of the gelling agents hydroxypropyl methylcellulose or carboxymethyl cellulose into Opt-RPG-CUB, forming repaglinide-loaded cubogels. Upon optimization, the cubogel with the highest desirability function, designated as Opt-RPG-Cubogel, was further evaluated for mucoadhesion, drug release kinetics, rheological properties, ex-vivo buccal permeation, and in-vivo drug permeation by confocal laser scanning microscopy and pharmacodynamic assessment in a streptozotocin-induced diabetic rat model. Results showed that Opt-RPG-CUB exhibited a SE% of 88.01 ± 3.92 %, PS of 252.55 ± 17.18 nm, and ZP of −31.13 ± 1.42 mV, with an extended drug release over 24 h and a cubic nanostructure. Opt-RPG-Cubogel exhibited strong mucoadhesion (>9 h), an extended drug release over 24 h, enhanced mucosal permeation, and improved tissue deposition. Confocal microscopy further confirmed deep mucosal penetration, while in-vivo studies demonstrated a significant reduction in blood glucose levels compared to the control. Overall, these findings highlight the potential of Opt-RPG-Cubogel as a promising buccoadhesive drug delivery system for efficient type II diabetes management. |
| format | Article |
| id | doaj-art-e4e3e328b2e44eb4967bc43cc3d1aec1 |
| institution | DOAJ |
| issn | 2590-1567 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj-art-e4e3e328b2e44eb4967bc43cc3d1aec12025-08-20T02:40:44ZengElsevierInternational Journal of Pharmaceutics: X2590-15672025-12-011010035710.1016/j.ijpx.2025.100357Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat modelNihal Farid Younes0Randa Latif1Alia Badawi2Khaled Hegazy3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt; Corresponding author at: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, P.O. Box 11562, Cairo, Egypt.Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptFaculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.The limited bioavailability of orally administered repaglinide presents a significant challenge in diabetes management, which can be addressed by developing a buccoadhesive drug delivery system. In this study, repaglinide-loaded cubosomes were prepared using a top-down approach and optimized via a 33 Box-Behnken design. The optimized formulation (Opt-RPG-CUB) was characterized for solubilization efficiency (SE%), particle size (PS), zeta potential (ZP), drug release kinetics, and morphology. To further enhance drug delivery, a 22 factorial design was utilized to incorporate varying concentrations of the gelling agents hydroxypropyl methylcellulose or carboxymethyl cellulose into Opt-RPG-CUB, forming repaglinide-loaded cubogels. Upon optimization, the cubogel with the highest desirability function, designated as Opt-RPG-Cubogel, was further evaluated for mucoadhesion, drug release kinetics, rheological properties, ex-vivo buccal permeation, and in-vivo drug permeation by confocal laser scanning microscopy and pharmacodynamic assessment in a streptozotocin-induced diabetic rat model. Results showed that Opt-RPG-CUB exhibited a SE% of 88.01 ± 3.92 %, PS of 252.55 ± 17.18 nm, and ZP of −31.13 ± 1.42 mV, with an extended drug release over 24 h and a cubic nanostructure. Opt-RPG-Cubogel exhibited strong mucoadhesion (>9 h), an extended drug release over 24 h, enhanced mucosal permeation, and improved tissue deposition. Confocal microscopy further confirmed deep mucosal penetration, while in-vivo studies demonstrated a significant reduction in blood glucose levels compared to the control. Overall, these findings highlight the potential of Opt-RPG-Cubogel as a promising buccoadhesive drug delivery system for efficient type II diabetes management.http://www.sciencedirect.com/science/article/pii/S2590156725000428RepaglinideCubosomesHydrogelsBuccal drug delivery systemIn-vivo hypoglycemic study |
| spellingShingle | Nihal Farid Younes Randa Latif Alia Badawi Khaled Hegazy Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model International Journal of Pharmaceutics: X Repaglinide Cubosomes Hydrogels Buccal drug delivery system In-vivo hypoglycemic study |
| title | Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model |
| title_full | Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model |
| title_fullStr | Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model |
| title_full_unstemmed | Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model |
| title_short | Optimized buccoadhesive repaglinide-loaded cubogel: In-vitro characterization and in-vivo hypoglycemic activity in a streptozotocin-induced diabetic rat model |
| title_sort | optimized buccoadhesive repaglinide loaded cubogel in vitro characterization and in vivo hypoglycemic activity in a streptozotocin induced diabetic rat model |
| topic | Repaglinide Cubosomes Hydrogels Buccal drug delivery system In-vivo hypoglycemic study |
| url | http://www.sciencedirect.com/science/article/pii/S2590156725000428 |
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