A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole
Tarek Abdelnapy Ahmed,1,2 Bader M Aljaeid1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Abstract: Oral ketoconazol...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-03-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/a-potential-in-situ-gel-formulation-loaded-with-novel-fabricated-polyl-peer-reviewed-article-IJN |
| _version_ | 1818845495165976576 |
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| author | Ahmed TA Aljaeid BM |
| author_facet | Ahmed TA Aljaeid BM |
| author_sort | Ahmed TA |
| collection | DOAJ |
| description | Tarek Abdelnapy Ahmed,1,2 Bader M Aljaeid1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Abstract: Oral ketoconazole therapy is commonly associated with serious hepatotoxicity. Improving ocular drug delivery could be sufficient to treat eye fungal infections. The purpose of this study was to develop optimized ketoconazole poly(lactide-co-glycolide) nanoparticles (NPs) with subsequent loading into in situ gel (ISG) formulation for ophthalmic drug delivery. Three formulation factors were optimized for their effect on particle size (Y1) and entrapment efficiency (Y2) utilizing central composite experimental design. Interaction among components was studied using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Ketoconazole crystalline state was studied using X-ray powder diffraction. Six different polymeric ISG formulations were prepared and loaded with either optimized NPs or a pure drug. The prepared ISG formulations were characterized for in vitro gelation, drug release and antifungal activity. The permeation through human epithelial cell line was also investigated. The results revealed that all the studied formulation parameters significantly affected Y1 and Y2 of the developed NPs. DSC and FTIR studies illustrated compatibility among NP components, while there was a change from the crystalline state to the amorphous state of the NPs. The in vitro release from the ISG formulations loaded with drug NPs showed sustained and enhanced drug release compared to pure drug formulations. In addition, ISG loaded with NPs showed enhanced anti-fungal activity compared to pure drug formulations. Alginate–chitosan ISG formulation loaded with optimized ketoconazole NPs illustrated higher drug permeation through epithelial cell lines and is considered as an effective ophthalmic drug delivery in the treatment of fungal eye infections. Keywords: ketoconazole, PLGA, nanoparticles, ISG, ophthalmic delivery |
| first_indexed | 2024-12-19T05:30:34Z |
| format | Article |
| id | doaj.art-38214b0740cc4dcc9bf050d3c788adf1 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T05:30:34Z |
| publishDate | 2017-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-38214b0740cc4dcc9bf050d3c788adf12022-12-21T20:34:15ZengDove Medical PressInternational Journal of Nanomedicine1178-20132017-03-01Volume 121863187531751A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazoleAhmed TAAljaeid BMTarek Abdelnapy Ahmed,1,2 Bader M Aljaeid1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Abstract: Oral ketoconazole therapy is commonly associated with serious hepatotoxicity. Improving ocular drug delivery could be sufficient to treat eye fungal infections. The purpose of this study was to develop optimized ketoconazole poly(lactide-co-glycolide) nanoparticles (NPs) with subsequent loading into in situ gel (ISG) formulation for ophthalmic drug delivery. Three formulation factors were optimized for their effect on particle size (Y1) and entrapment efficiency (Y2) utilizing central composite experimental design. Interaction among components was studied using differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Ketoconazole crystalline state was studied using X-ray powder diffraction. Six different polymeric ISG formulations were prepared and loaded with either optimized NPs or a pure drug. The prepared ISG formulations were characterized for in vitro gelation, drug release and antifungal activity. The permeation through human epithelial cell line was also investigated. The results revealed that all the studied formulation parameters significantly affected Y1 and Y2 of the developed NPs. DSC and FTIR studies illustrated compatibility among NP components, while there was a change from the crystalline state to the amorphous state of the NPs. The in vitro release from the ISG formulations loaded with drug NPs showed sustained and enhanced drug release compared to pure drug formulations. In addition, ISG loaded with NPs showed enhanced anti-fungal activity compared to pure drug formulations. Alginate–chitosan ISG formulation loaded with optimized ketoconazole NPs illustrated higher drug permeation through epithelial cell lines and is considered as an effective ophthalmic drug delivery in the treatment of fungal eye infections. Keywords: ketoconazole, PLGA, nanoparticles, ISG, ophthalmic deliveryhttps://www.dovepress.com/a-potential-in-situ-gel-formulation-loaded-with-novel-fabricated-polyl-peer-reviewed-article-IJNKetoconazolePLGAnanoparticlesISGophthalmic delivery |
| spellingShingle | Ahmed TA Aljaeid BM A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole International Journal of Nanomedicine Ketoconazole PLGA nanoparticles ISG ophthalmic delivery |
| title | A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole |
| title_full | A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole |
| title_fullStr | A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole |
| title_full_unstemmed | A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole |
| title_short | A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole |
| title_sort | potential in situ gel formulation loaded with novel fabricated poly lactide co glycolide nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole |
| topic | Ketoconazole PLGA nanoparticles ISG ophthalmic delivery |
| url | https://www.dovepress.com/a-potential-in-situ-gel-formulation-loaded-with-novel-fabricated-polyl-peer-reviewed-article-IJN |
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