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  2. Peptide-based hydrogel co-assembled with antibody-drug for enhanced retinal cell uptake and attenuated experimental autoimmune uveitis

Peptide-based hydrogel co-assembled with antibody-drug for enhanced retinal cell uptake and attenuated experimental autoimmune uveitis

  • Eur J Pharm Biopharm. 2025 Mar 5:114691. doi: 10.1016/j.ejpb.2025.114691.
Mali Dai 1 Pengyuan Du 1 Yijing Li 1 Xiaiting Wang 1 Jinrun Chen 1 Hui Liu 1 Wenqiao Zhang 1 Jianhong Zhou 1 Xingyi Li 2 Yuqin Wang 3
Affiliations

Affiliations

  • 1 National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
  • 2 National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: lixingyi_1984@mail.eye.ac.cn.
  • 3 National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: wangyuqin@eye.ac.cn.
Abstract

Effective treatment of chronic posterior ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration requires improvements in targeted drug delivery strategies. This study introduces a novel injectable drug delivery system co-assembled with a peptide-based hydrogel and secukinumab (SEK), an IL-17A neutralising monoclonal antibody, targeting retinal pigmented epithelium (RPE) cells. Compared to a SEK solution, the SEK loaded hydrogel significantly enhanced the protein uptake (3.7 times higher) by RPE cells in an inflammatory state after 24 h of treatment and increased the drug concentration in retinal tissues during 20 d of treatment. A single intravitreal injection of the SEK loaded hydrogel effectively suppressed inflammation in a uveitis model. It also reduced the immunoreactivity of microglia and T helper 17 cells, preserved the integrity of the blood-retina barrier, mitigated retinal cell Apoptosis, and facilitated the recovery of the retinal function. This delivery system comprising an antibody-drug co-assembled with a peptide-based hydrogel shows promising potential for targeting the retina and treating complex chronic posterior ocular diseases.

Keywords

Antibody-drug; Chronic posterior ocular disease; Peptide-based hydrogel; Retinal pigmented epithelium; Targeted drug delivery.

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