Formulation of Hesperidin‐Loaded In‐situ Gel for Ocular Drug Delivery: A Comprehensive Study

Gözcü S., Polat H. K., Gültekin Y., Ünal S., Karakuyu N. F., Köngül Şafak E., ...Daha Fazla

JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, cilt.104, ss.5846-5859, 2024 (SCI-Expanded)

Özet

Background

Allergic conjunctivitis is one of the most common eye disorders. Different drugs are used for its treatment. Hesperidin is an active substance isolated from Citrus sinensis L. (Rutaceae) fruit peels, with known anti-inflammatory activity but low solubility, it was complexed with cyclodextrin and encapsulated in-situ gel to extend the eye duration.

Results

The optimized formulation comprised 1% hesperidin, 1.5% hydroxyethyl cellulose, and 16% poloxamer 407. The viscosity at 25°C was 492±82, at 35°C was 8875±248, pH was 7.01±0.03, gelation temperature was 34±1.3°C, and gelation time was 33±1.2 seconds. In vitro release exhibited 66% release within the initial two hours with a burst effect. With LOX inhibition test, it was determined that hesperidin showed activity at high doses on leukotyrens seen in the body in allergic diseases. In cell culture studies, the hesperidin cyclodextrin complex loaded in-situ gel (Poloxamer 16%, HEC 1.5%) (BRN9-CD) enhanced cell viability compared to the hesperidin solution. It was determined that BRN9-CD did not cause any irritation in the ocular tissues in the Draize test.

Conclusion

The findings of this study demonstrate the promising potential of the in-situ gel formulation of hesperidin in terms of ease of application and residence time on the ocular surface. Due to its notable LOX inhibition activity and positive outcomes in the in vivo Draize test, it holds promise for incorporation into pharmaceutical formulations.