Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity
Background: Gold nanoparticles (NPs) have drawn great attention in the area of biomedical research with their relatively safe and versatile properties. This study aimed to synthesize long-lasting exendin-4-coated gold NPs (EX-ABD-AFF-GoldNPs) and evaluate their anti-diabetic effects in vivo. Methods...
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MDPI AG
2024-11-01
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| Online Access: | https://www.mdpi.com/1424-8247/17/11/1475 |
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| author | Reeju Amatya Amala Joseph Gu Seob Roh Yassmine Benmokadem Kyoung Ah Min Meong Cheol Shin |
| author_facet | Reeju Amatya Amala Joseph Gu Seob Roh Yassmine Benmokadem Kyoung Ah Min Meong Cheol Shin |
| author_sort | Reeju Amatya |
| collection | DOAJ |
| description | Background: Gold nanoparticles (NPs) have drawn great attention in the area of biomedical research with their relatively safe and versatile properties. This study aimed to synthesize long-lasting exendin-4-coated gold NPs (EX-ABD-AFF-GoldNPs) and evaluate their anti-diabetic effects in vivo. Methods: In the present study, EX-ABD-AFF-GoldNPs were synthesized using a simple one-step aqueous reduction method. The physical characterization of the prepared particles verified the successful formation of the EX-ABD-AFF-GoldNPs through dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet–visible (UV-VIS) light spectroscopy, and Fourier transform infrared spectroscopy (FTIR). The anti-hyperglycemic and anti-obesity effects were assessed in high-fat diet (HFD)-fed obese diabetic mice. Additionally, pharmacokinetics (PK) and biodistribution studies were performed to verify the long-lasting properties. Results: The EX-ABD-AFF-GoldNPs were conglomerates of smaller globular-shaped particles, and the average size was 110(±14) nm, based on the TEM images. Safety assessments using Min6, HepG2, and B16F10 cell lines demonstrated low cytotoxicity, with over 80% cell viability up to the highest tested concentration of 150 μg/mL (as EX-ABD-AFF). Notably, the animal studies showed that the EX-ABD-AFF-GoldNPs exhibited significant hypoglycemic activity, comparable to the EX-ABD-AFF, in the HFD-fed mice. A 4-week treatment with EX-ABD-AFF-GoldNPs produced similar reductions in blood glucose and body weight to the EX-ABD-AFF, without any apparent toxicity. Furthermore, the PK and biodistribution study results confirmed the long-lasting properties (plasma half-life: 43.6 h) of the particles. Conclusions: Overall, this study demonstrated that the preparation of therapeutic protein-loaded gold NPs is feasible and, despite their much larger size compared with the protein, EX-ABD-AFF-GoldNPs can be successfully absorbed through the subcutaneous route and show nearly equivalent hypoglycemic activity to the EX-ABD-AFF protein. Finally, this study showed that long-lasting properties could be acquired by only coating EX-ABD-AFF onto gold NPs. |
| format | Article |
| id | doaj-art-4226df8ab2a54b5c9ead09eead558cdd |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-4226df8ab2a54b5c9ead09eead558cdd2025-08-20T02:48:02ZengMDPI AGPharmaceuticals1424-82472024-11-011711147510.3390/ph17111475Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic ActivityReeju Amatya0Amala Joseph1Gu Seob Roh2Yassmine Benmokadem3Kyoung Ah Min4Meong Cheol Shin5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju 52828, Gyeongnam, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju 52828, Gyeongnam, Republic of KoreaDepartment of Anatomy and Convergence Medical Science, Metabolic Dysfunction Liver Disease Research Center, Institute of Medical Science, College of Medicine, Gyeongsang National University, 816-15 Jinju Daero, Jinju 52727, Gyeongnam, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae 50834, Gyeongnam, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju 52828, Gyeongnam, Republic of KoreaBackground: Gold nanoparticles (NPs) have drawn great attention in the area of biomedical research with their relatively safe and versatile properties. This study aimed to synthesize long-lasting exendin-4-coated gold NPs (EX-ABD-AFF-GoldNPs) and evaluate their anti-diabetic effects in vivo. Methods: In the present study, EX-ABD-AFF-GoldNPs were synthesized using a simple one-step aqueous reduction method. The physical characterization of the prepared particles verified the successful formation of the EX-ABD-AFF-GoldNPs through dynamic light scattering (DLS), transmission electron microscopy (TEM), ultraviolet–visible (UV-VIS) light spectroscopy, and Fourier transform infrared spectroscopy (FTIR). The anti-hyperglycemic and anti-obesity effects were assessed in high-fat diet (HFD)-fed obese diabetic mice. Additionally, pharmacokinetics (PK) and biodistribution studies were performed to verify the long-lasting properties. Results: The EX-ABD-AFF-GoldNPs were conglomerates of smaller globular-shaped particles, and the average size was 110(±14) nm, based on the TEM images. Safety assessments using Min6, HepG2, and B16F10 cell lines demonstrated low cytotoxicity, with over 80% cell viability up to the highest tested concentration of 150 μg/mL (as EX-ABD-AFF). Notably, the animal studies showed that the EX-ABD-AFF-GoldNPs exhibited significant hypoglycemic activity, comparable to the EX-ABD-AFF, in the HFD-fed mice. A 4-week treatment with EX-ABD-AFF-GoldNPs produced similar reductions in blood glucose and body weight to the EX-ABD-AFF, without any apparent toxicity. Furthermore, the PK and biodistribution study results confirmed the long-lasting properties (plasma half-life: 43.6 h) of the particles. Conclusions: Overall, this study demonstrated that the preparation of therapeutic protein-loaded gold NPs is feasible and, despite their much larger size compared with the protein, EX-ABD-AFF-GoldNPs can be successfully absorbed through the subcutaneous route and show nearly equivalent hypoglycemic activity to the EX-ABD-AFF protein. Finally, this study showed that long-lasting properties could be acquired by only coating EX-ABD-AFF onto gold NPs.https://www.mdpi.com/1424-8247/17/11/1475exendin-4goldnanoparticlediabeteslong-lasting |
| spellingShingle | Reeju Amatya Amala Joseph Gu Seob Roh Yassmine Benmokadem Kyoung Ah Min Meong Cheol Shin Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity Pharmaceuticals exendin-4 gold nanoparticle diabetes long-lasting |
| title | Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity |
| title_full | Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity |
| title_fullStr | Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity |
| title_full_unstemmed | Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity |
| title_short | Long-Lasting Exendin-4-Coated Gold Nanoparticles: Synthesis and In Vivo Evaluation of Hypoglycemic Activity |
| title_sort | long lasting exendin 4 coated gold nanoparticles synthesis and in vivo evaluation of hypoglycemic activity |
| topic | exendin-4 gold nanoparticle diabetes long-lasting |
| url | https://www.mdpi.com/1424-8247/17/11/1475 |
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