Dexamethasone-loaded fibroin nanoparticles promote retinal reattachment in rats by regulating the Th17/Treg balance

Retinal detachment (RD) is a common acute blinding eye disease, and dexamethasone (DEX), an adrenocorticosteroid, shows protective effects against RD. However, its poor water solubility and low bioavailability limit its effectiveness. To address this, we developed SF@DEX nanomaterials and investigated their therapeutic potential and mechanisms in RD. The nanomaterials were successfully synthesized and characterized, achieving 90% encapsulation efficiency and releasing 60% of DEX within 12 h.<i>In vitro</i>, phagocytosis was measured by flow cytometry, and enzyme-linked immunosorbent assay determined interleukin-17 (IL-17) and interleukin-10 (IL-10) levels. A rat RD model was established surgically, followed by oral administration of silk fibroin (SF), SF@DEX, and DEX. Polymerase chain reaction (PCR) assessed IL-17A and forkhead box P3 (FOXP3) expression, while Western blot analysed transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1), IL-10, IL-17A, and FOXP3 levels. Apoptosis of retinal ganglion cells was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and confocal microscopy detected colocalization of IL-17A and FOXP3. SF@DEX treatment significantly reduced Th17 cells and IL-17A while increasing Tregs, FOXP3, TGF-<i>β</i>1, and IL-10 levels. The severity of RD in rats was notably alleviated by SF@DEX, demonstrating its anti-inflammatory effects through modulation of the Th17/Treg immune balance. These results highlight SF@DEX as a promising nano-based therapy for RD.