Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide
Abstract Brinzolamide is a widely used treatment for glaucoma, but its effectiveness relies on at least twice-daily dosing, which can be challenging for patient adherence. To overcome this limitation, we developed an injectable hydrogel-based delivery system designed to maintain therapeutic drug lev...
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| Format: | Article |
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Springer
2025-05-01
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| Series: | Journal of Materials Science: Materials in Medicine |
| Online Access: | https://doi.org/10.1007/s10856-025-06896-1 |
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| author | Jiahao Xu Linyu Long Xiaoyu Zhou Xinyue Zhang Li Liao Dan Ji Xuanchu Duan |
| author_facet | Jiahao Xu Linyu Long Xiaoyu Zhou Xinyue Zhang Li Liao Dan Ji Xuanchu Duan |
| author_sort | Jiahao Xu |
| collection | DOAJ |
| description | Abstract Brinzolamide is a widely used treatment for glaucoma, but its effectiveness relies on at least twice-daily dosing, which can be challenging for patient adherence. To overcome this limitation, we developed an injectable hydrogel-based delivery system designed to maintain therapeutic drug levels with a single administration. This approach aims to simplify treatment and improve clinical outcomes. Brinzolamide-loaded polyethylene glycol poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles were encapsulated within a hydrogel synthesized through the crosslinking of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMC). In vitro studies were conducted to assess the nanoparticles’ characterization, release profile, and biocompatibility. In a steroid-induced high intraocular pressure (IOP) mouse model, the efficacy of a single subconjunctival injection in lowering IOP was evaluated. Additionally, both cellular and animal biocompatibility were assessed. The brinzolamide-loaded hydrogel system (Hydrogel@Brz) contained nanoparticles with an average diameter of 40.76 nm, exhibiting a stable size distribution and a spherical morphology. The hydrogel demonstrated excellent injectability, self-healing properties, and a porous structure conducive to nanoparticle encapsulation. In vitro release studies revealed a sustained drug release of 86% over 14 days. No cytotoxicity was observed in human primary trabecular meshwork cells (HTMCs), human Tenon’s capsule fibroblasts (HTFs), or the retinal ganglion cell line R28. In vivo, a single injection led to a prolonged IOP reduction lasting up to 21 days. No signs of drug toxicity were detected in ocular tissue sections, transverse optic nerve sections under transmission electron microscopy, or pathology slides of various organs. The brinzolamide-loaded hydrogel has demonstrated promising potential for sustained drug delivery and effective intraocular pressure reduction while maintaining good biocompatibility. However, further studies in larger animal models and long-term evaluations are needed to confirm its clinical applicability. Graphical Abstract |
| format | Article |
| id | doaj-art-2e0ee1685ad44475ba722dae70bbc4ef |
| institution | OA Journals |
| issn | 1573-4838 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Materials Science: Materials in Medicine |
| spelling | doaj-art-2e0ee1685ad44475ba722dae70bbc4ef2025-08-20T02:29:26ZengSpringerJournal of Materials Science: Materials in Medicine1573-48382025-05-0136111210.1007/s10856-025-06896-1Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamideJiahao Xu0Linyu Long1Xiaoyu Zhou2Xinyue Zhang3Li Liao4Dan Ji5Xuanchu Duan6Aier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye HospitalAier Eye Hospital Group Co. Ltd.Aier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye HospitalAier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye HospitalAier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye HospitalDepartment of Ophthalmology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal UniversityAier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye HospitalAbstract Brinzolamide is a widely used treatment for glaucoma, but its effectiveness relies on at least twice-daily dosing, which can be challenging for patient adherence. To overcome this limitation, we developed an injectable hydrogel-based delivery system designed to maintain therapeutic drug levels with a single administration. This approach aims to simplify treatment and improve clinical outcomes. Brinzolamide-loaded polyethylene glycol poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles were encapsulated within a hydrogel synthesized through the crosslinking of oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMC). In vitro studies were conducted to assess the nanoparticles’ characterization, release profile, and biocompatibility. In a steroid-induced high intraocular pressure (IOP) mouse model, the efficacy of a single subconjunctival injection in lowering IOP was evaluated. Additionally, both cellular and animal biocompatibility were assessed. The brinzolamide-loaded hydrogel system (Hydrogel@Brz) contained nanoparticles with an average diameter of 40.76 nm, exhibiting a stable size distribution and a spherical morphology. The hydrogel demonstrated excellent injectability, self-healing properties, and a porous structure conducive to nanoparticle encapsulation. In vitro release studies revealed a sustained drug release of 86% over 14 days. No cytotoxicity was observed in human primary trabecular meshwork cells (HTMCs), human Tenon’s capsule fibroblasts (HTFs), or the retinal ganglion cell line R28. In vivo, a single injection led to a prolonged IOP reduction lasting up to 21 days. No signs of drug toxicity were detected in ocular tissue sections, transverse optic nerve sections under transmission electron microscopy, or pathology slides of various organs. The brinzolamide-loaded hydrogel has demonstrated promising potential for sustained drug delivery and effective intraocular pressure reduction while maintaining good biocompatibility. However, further studies in larger animal models and long-term evaluations are needed to confirm its clinical applicability. Graphical Abstracthttps://doi.org/10.1007/s10856-025-06896-1 |
| spellingShingle | Jiahao Xu Linyu Long Xiaoyu Zhou Xinyue Zhang Li Liao Dan Ji Xuanchu Duan Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide Journal of Materials Science: Materials in Medicine |
| title | Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide |
| title_full | Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide |
| title_fullStr | Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide |
| title_full_unstemmed | Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide |
| title_short | Sustained intraocular pressure-lowering effect and biocompatibility of a single subconjunctival administration of hydrogel-encapsulated nano-brinzolamide |
| title_sort | sustained intraocular pressure lowering effect and biocompatibility of a single subconjunctival administration of hydrogel encapsulated nano brinzolamide |
| url | https://doi.org/10.1007/s10856-025-06896-1 |
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