Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis
<b>Background/Objectives:</b> Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an...
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2025-04-01
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| author | Raffaele Conte Anna Valentino Fabrizia Sepe Francesco Gianfreda Roberta Condò Loredana Cerroni Anna Calarco Gianfranco Peluso |
| author_facet | Raffaele Conte Anna Valentino Fabrizia Sepe Francesco Gianfreda Roberta Condò Loredana Cerroni Anna Calarco Gianfranco Peluso |
| author_sort | Raffaele Conte |
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| description | <b>Background/Objectives:</b> Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. <b>Methods:</b> A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. <b>Results:</b> RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. <b>Conclusions:</b> The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. |
| format | Article |
| id | doaj-art-6c4b023ba8e24b6b8d71fe022dd4847a |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-6c4b023ba8e24b6b8d71fe022dd4847a2025-08-20T03:47:53ZengMDPI AGBiomedicines2227-90592025-04-01135105910.3390/biomedicines13051059Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related PeriodontitisRaffaele Conte0Anna Valentino1Fabrizia Sepe2Francesco Gianfreda3Roberta Condò4Loredana Cerroni5Anna Calarco6Gianfranco Peluso7Research Institute on Terrestrial Ecosystems (IRET)-CNR, Via Pietro Castellino 111, 80131 Naples, ItalyResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via Pietro Castellino 111, 80131 Naples, ItalyResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via Pietro Castellino 111, 80131 Naples, ItalyDepartment of System Medicine, University of Rome “Tor Vergata”, Via Montpellier, 1, 00133 Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier, 1, 00133 Rome, ItalyDepartment of Clinical Sciences and Translational Medicine, University of Rome “Tor Vergata”, Via Montpellier, 1, 00133 Rome, ItalyResearch Institute on Terrestrial Ecosystems (IRET)-CNR, Via Pietro Castellino 111, 80131 Naples, ItalyFaculty of Medicine and Surgery, Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, Italy<b>Background/Objectives:</b> Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. <b>Methods:</b> A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. <b>Results:</b> RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. <b>Conclusions:</b> The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease.https://www.mdpi.com/2227-9059/13/5/1059diabetes-related periodontitisresveratrolsolid lipid nanoparticleshyaluronic acid hydrogelanti-inflammatory therapyantioxidant therapy |
| spellingShingle | Raffaele Conte Anna Valentino Fabrizia Sepe Francesco Gianfreda Roberta Condò Loredana Cerroni Anna Calarco Gianfranco Peluso Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis Biomedicines diabetes-related periodontitis resveratrol solid lipid nanoparticles hyaluronic acid hydrogel anti-inflammatory therapy antioxidant therapy |
| title | Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis |
| title_full | Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis |
| title_fullStr | Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis |
| title_full_unstemmed | Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis |
| title_short | Resveratrol-Loaded Solid Lipid Nanoparticles Reinforced Hyaluronic Hydrogel: Multitarget Strategy for the Treatment of Diabetes-Related Periodontitis |
| title_sort | resveratrol loaded solid lipid nanoparticles reinforced hyaluronic hydrogel multitarget strategy for the treatment of diabetes related periodontitis |
| topic | diabetes-related periodontitis resveratrol solid lipid nanoparticles hyaluronic acid hydrogel anti-inflammatory therapy antioxidant therapy |
| url | https://www.mdpi.com/2227-9059/13/5/1059 |
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