In situ Forming Nanoemulgel for Diabetic Retinopathy: Development, characterization, and in vitro efficacy assessment

Diabetic retinopathy, the most common microvascular complication of diabetes mellitus, is the leading cause of vision impairment worldwide. Flavonoids with antioxidant properties have been shown to slow its progression. Myricetin, a flavonoid polyphenolic compound, possesses antioxidant properties, but its clinical use in ocular delivery is limited by poor aqueous solubility, stability, and bioavailability. Recently, in situ gels have gained interest as ocular drug delivery vehicles due to their ease of installation and sustained drug release. This study aimed to develop a myricetin-loaded thermoresponsive in situ nanoemulgel to enhance its efficacy in treating diabetic retinopathy. Nanoemulsions were developed via aqueous phase titration using Sefsol 218 as the oil phase, Kolliphore RH40 as the surfactant, and PEG 400 as the co-surfactant. Physicochemical evaluations identified formulation batch ISG17, consisting of 10% oil phase, 30% S_mix (1:2), and 60% distilled water, as the optimal formulation. The developed in situ nanoemulgel showed significant enhancement in corneal permeation and retention, which was further confirmed by fluorescence microscopy. Ocular tolerability was demonstrated through corneal hydration tests and histopathology investigations. The antioxidant potential of the myricetin-loaded nanoemulgel was assessed using the DPPH assay. Myricetin was found to be an efficient antioxidant, as indicated by its IC₅₀ values compared to ascorbic acid. The MTT cell viability assay results showed that the developed formulation effectively inhibits the proliferation of Y79 retinoblastoma cells, demonstrating comparable efficacy to the standard marketed preparation Avastin (Bevacizumab injection). In conclusion, the nanoemulsion formulation containing a thermoresponsive polymer for in situ gelling presents a promising drug delivery system, offering superior therapeutic efficacy and better patient compliance for the treatment of diabetic retinopathy.