Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept
Oleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tr...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/16/1/153 |
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| author | Hend Abd-Allah John Youshia Gehad A. Abdel Jaleel Azza Hassan Mevidette El Madani Maha Nasr |
| author_facet | Hend Abd-Allah John Youshia Gehad A. Abdel Jaleel Azza Hassan Mevidette El Madani Maha Nasr |
| author_sort | Hend Abd-Allah |
| collection | DOAJ |
| description | Oleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tract. Therefore, loading oleuropein onto chitosan nanoparticles is expected to enhance its biological efficiency. Oleuropein-loaded chitosan nanoparticles were prepared and characterized for particle size, surface charge, in vitro release, and anti-inflammatory activity. Their in vivo efficacy was assessed by measuring specific inflammatory and protective biomarkers, along with histopathological examination. The optimum oleuropein chitosan nanoparticles were cationic, had a size of 174.3 ± 2.4 nm and an entrapment efficiency of 92.81%, and released 70% of oleuropein within 8 h. They recorded a lower IC50 in comparison to oleuropein solutions for membrane stabilization of RBCs (22.6 vs. 25.6 µg/mL) and lipoxygenase inhibition (7.17 vs. 15.6 µg/mL). In an ethanol-induced gastric ulcer in vivo model, they decreased IL-1β, TNF-α, and TBARS levels by 2.1, 1.7, and 1.3 fold, respectively, in comparison to increments caused by exposure to ethanol. Moreover, they increased prostaglandin E2 and catalase enzyme levels by 2.4 and 3.8 fold, respectively. Immunohistochemical examination showed that oleuropein chitosan nanoparticles markedly lowered the expression of IL-6 and caspase-3 in gastric tissues in comparison to oleuropein solution. Overall, oleuropein chitosan nanoparticles showed superior gastroprotective effects to oleuropein solution since comparable effects were demonstrated at a 12-fold lower drug dose, delineating that chitosan nanoparticles indeed enhanced the potency of oleuropein as a gastroprotective agent. |
| first_indexed | 2024-03-08T10:37:36Z |
| format | Article |
| id | doaj.art-8a8ceedcac644e8a9e4acbd30c1ebc42 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T10:37:36Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8a8ceedcac644e8a9e4acbd30c1ebc422024-01-26T18:08:55ZengMDPI AGPharmaceutics1999-49232024-01-0116115310.3390/pharmaceutics16010153Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of ConceptHend Abd-Allah0John Youshia1Gehad A. Abdel Jaleel2Azza Hassan3Mevidette El Madani4Maha Nasr5Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptPharmacology Department, National Research Centre (NRC), Giza 12622, EgyptPathology Department, Faculty of Veterinary Medicine, Cairo University, Cairo 12613, EgyptPharmacology Department, National Research Centre (NRC), Giza 12622, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptOleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tract. Therefore, loading oleuropein onto chitosan nanoparticles is expected to enhance its biological efficiency. Oleuropein-loaded chitosan nanoparticles were prepared and characterized for particle size, surface charge, in vitro release, and anti-inflammatory activity. Their in vivo efficacy was assessed by measuring specific inflammatory and protective biomarkers, along with histopathological examination. The optimum oleuropein chitosan nanoparticles were cationic, had a size of 174.3 ± 2.4 nm and an entrapment efficiency of 92.81%, and released 70% of oleuropein within 8 h. They recorded a lower IC50 in comparison to oleuropein solutions for membrane stabilization of RBCs (22.6 vs. 25.6 µg/mL) and lipoxygenase inhibition (7.17 vs. 15.6 µg/mL). In an ethanol-induced gastric ulcer in vivo model, they decreased IL-1β, TNF-α, and TBARS levels by 2.1, 1.7, and 1.3 fold, respectively, in comparison to increments caused by exposure to ethanol. Moreover, they increased prostaglandin E2 and catalase enzyme levels by 2.4 and 3.8 fold, respectively. Immunohistochemical examination showed that oleuropein chitosan nanoparticles markedly lowered the expression of IL-6 and caspase-3 in gastric tissues in comparison to oleuropein solution. Overall, oleuropein chitosan nanoparticles showed superior gastroprotective effects to oleuropein solution since comparable effects were demonstrated at a 12-fold lower drug dose, delineating that chitosan nanoparticles indeed enhanced the potency of oleuropein as a gastroprotective agent.https://www.mdpi.com/1999-4923/16/1/153oleuropeinchitosan nanoparticlesgastric ulceranti-inflammatoryantioxidant |
| spellingShingle | Hend Abd-Allah John Youshia Gehad A. Abdel Jaleel Azza Hassan Mevidette El Madani Maha Nasr Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept Pharmaceutics oleuropein chitosan nanoparticles gastric ulcer anti-inflammatory antioxidant |
| title | Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept |
| title_full | Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept |
| title_fullStr | Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept |
| title_full_unstemmed | Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept |
| title_short | Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept |
| title_sort | gastroprotective chitosan nanoparticles loaded with oleuropein an in vivo proof of concept |
| topic | oleuropein chitosan nanoparticles gastric ulcer anti-inflammatory antioxidant |
| url | https://www.mdpi.com/1999-4923/16/1/153 |
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