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
  • 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: [email protected].
  • 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: [email protected].
PMID: 40054506 DOI: 10.1016/j.ejpb.2025.114691
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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