Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations
<b>Background/Objectives:</b> Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate...
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2025-03-01
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| author | Mennatullah M. Faisal Eman Gomaa Mohamed S. Attia Rana M. Abdelnaby Adel Ehab Ibrahim Ahmed Al-Harrasi Sami El Deeb Al Zahraa G. Al Ashmawy |
| author_facet | Mennatullah M. Faisal Eman Gomaa Mohamed S. Attia Rana M. Abdelnaby Adel Ehab Ibrahim Ahmed Al-Harrasi Sami El Deeb Al Zahraa G. Al Ashmawy |
| author_sort | Mennatullah M. Faisal |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. <b>Methods:</b> The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. <b>Results:</b> The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin (−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. <b>Conclusions:</b> This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients. |
| format | Article |
| id | doaj-art-17d1ea17104c4aebafe2c91b3b8d678f |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-17d1ea17104c4aebafe2c91b3b8d678f2025-08-20T02:42:24ZengMDPI AGPharmaceutics1999-49232025-03-0117335010.3390/pharmaceutics17030350Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo EvaluationsMennatullah M. Faisal0Eman Gomaa1Mohamed S. Attia2Rana M. Abdelnaby3Adel Ehab Ibrahim4Ahmed Al-Harrasi5Sami El Deeb6Al Zahraa G. Al Ashmawy7Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment Pharmaceutical Chemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, EgyptNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, P.O. Box 33, Nizwa 616, OmanNatural and Medical Sciences Research Center, University of Nizwa, Birkat Al Mauz, P.O. Box 33, Nizwa 616, OmanInstitute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, 38106 Brunswick, GermanyDepartment of Pharmaceutics, Faculty of Pharmacy, El Saleheya El Gadida University, El Saleheya El Gadida 44813, Egypt<b>Background/Objectives:</b> Hyperlipidemia is a silent threat lurking in the bloodstream of millions worldwide. The nano-based platform has emerged as a promising drug delivery technology. Repaglinide, an anti-diabetic drug, was investigated recently as an antihyperlipidemic candidate that could supersede the available antihyperlipidemic drugs. Our goal was to optimize albumin-based nanoparticles loaded with Repaglinide for parenteral delivery and conduct in silico and in vivo studies to explore the efficacy of Repaglinide for the management of hyperlipidemia along with its anti-diabetic effect. <b>Methods:</b> The impact of three independent factors, the albumin%, acetone volume, and glutaraldehyde/albumin, on the particle size, zeta potential, and entrapment efficiency was investigated. <b>Results:</b> The optimized formulation was spherical, homogenous of an average diameter (~181.86 nm) with a narrow size distribution, a zeta potential of −24.26 mV, and 76.37% as the EE%. The in vitro release of Repaglinide from nanoparticles showed a sustained release pattern for 168 h, with an initial burst release after 24 h, and was fitted to the Fickian diffusion mechanism. A molecular docking simulation showed a strong affinity to several protein targets, and the results were very promising, where Repaglinide gave a score of −7.70 Kcal/mol compared to Mevastatin (−6.71 Kcal/mol) and Atorvastatin (−8.36 Kcal/mol). On conducting in vivo studies on animal models, the optimized formula recorded a statistically significant decrease in the serum levels of total cholesterol, triglyceride, and low-density lipoproteins, with an increased high-density lipoprotein. <b>Conclusions:</b> This study suggested albumin nanoparticles as potential nanocarriers for the parenteral delivery of Repaglinide to ameliorate its antihyperlipidemic benefits, especially in diabetic patients.https://www.mdpi.com/1999-4923/17/3/350factorial designatherosclerosisalbuminnanoparticlesin silicotriglycerides |
| spellingShingle | Mennatullah M. Faisal Eman Gomaa Mohamed S. Attia Rana M. Abdelnaby Adel Ehab Ibrahim Ahmed Al-Harrasi Sami El Deeb Al Zahraa G. Al Ashmawy Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations Pharmaceutics factorial design atherosclerosis albumin nanoparticles in silico triglycerides |
| title | Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations |
| title_full | Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations |
| title_fullStr | Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations |
| title_full_unstemmed | Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations |
| title_short | Albumin-Based Nanoparticles with Factorial Design as a Promising Approach for Remodeled Repaglinide: Evidence from In Silico, In Vitro, and In Vivo Evaluations |
| title_sort | albumin based nanoparticles with factorial design as a promising approach for remodeled repaglinide evidence from in silico in vitro and in vivo evaluations |
| topic | factorial design atherosclerosis albumin nanoparticles in silico triglycerides |
| url | https://www.mdpi.com/1999-4923/17/3/350 |
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