Oxidative stress, reactive oxygen species generation,
and overexpression
of VEGF are signatory events in diabetic retinopathy. The downregulation
of VEGF and anti-inflammatory action pave the way for diabetic retinopathy
(DR) therapy. In that, lower absorption kinetics of melatonin limits
its immense therapeutic potential. Hence, we have demonstrated a reverse
microemulsion method to synthesize melatonin-loaded polydopamine nanoparticles
to replenish both at a single platform with an improved melatonin
delivery profile. The study has evaluated in vitro and in vivo protection efficiency of biocompatible
melatonin-loaded polydopamine nanoparticles (MPDANPs). The protection
mechanism was explained by downregulation of VEGF, CASPASE3, and PKCδ
against high-glucose/streptozotocin (STZ)-induced insults, in vitro and in vivo. The anti-inflammatory
and antiangiogenic effect and potential of MPDANPs to enhance melatonin in vivo stability with prolonged circulation time have proved
MPDANPs as a potential therapeutic candidate in DR management. The
DR therapeutic potential of MPDANPs has been arbitrated by improving
the bioavailability of melatonin and inhibition of VEGF–PKCδ
crosstalk in vivo.