Insulin-imprinted hydrogel eye drop restores tear secretion, reduces inflammation in rat Dry Eye Syndrome

Effective treatment for Dry Eye Syndrome (DES) remains a significant challenge due to the rapid clearance of topical formulations from the ocular surface by blinking and tear turnover. This leads to inadequate drug concentrations and necessitates frequent reapplication, reducing patient compliance and therapeutic efficacy. Current standard-of-care often provides symptomatic relief but struggles with sustained delivery and addressing underlying ocular surface damage and inflammation. Insulin, known for its trophic and anti-inflammatory properties, holds promise for ocular surface repair, but its delivery requires innovative platforms to ensure prolonged contact and bioavailability.

Researchers developed a dual pH- and temperature-responsive composite hydrogel, CPN-IMIP, by integrating chitosan (Cs)-grafted poly-N-isopropylacrylamide (PNIPAAm) with alginate-based insulin-imprinted microgels (IMIP). They characterized the hydrogel's properties, including rheology, swelling behavior, wettability, and biodegradation. Insulin release kinetics were assessed at varying pH and temperatures. The system's biocompatibility was evaluated using human corneal epithelial cell viability assays. Finally, the therapeutic efficacy was tested in a rat DES model, where effects on tear secretion, corneal integrity, and inflammation were measured.

The incorporation of IMIP particles significantly tuned the hydrogel's properties, increasing viscosity from 3.1 mPa·s (CPN-IMIP10) to 37.3 mPa·s (CPN-IMIP35), which is crucial for ocular retention. The hydrogel exhibited a desirable sol-gel transition between 25 and 37°C, allowing easy flowability at room temperature and rapid gelation on the ocular surface. All CPN-IMIP hydrogels showed elastic-dominant behavior (G' > G″), confirming a stable, shear-resistant network. Insulin release was precisely tunable based on environmental conditions: > At pH 6.4 and 25°C, diffusion governed delivery, releasing 29.8 ± 3.6% of insulin over 48 hours. In contrast, at pH 7.4 and 37°C, swelling-controlled release predominated, achieving 54.4 ± 4.8% release over the same period. In the rat DES model, the composite hydrogels supported human corneal epithelial cell viability, significantly enhanced tear secretion, preserved corneal integrity, and reduced inflammation.