Abstract
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% Smix (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.
Keywords
antidiabetic drugs - drug delivery - apoptosis
