Improved Melatonin Delivery by a Size-Controlled Polydopamine Nanoformulation Attenuates Preclinical Diabetic Retinopathy

Abstract

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.

Melatonin-Polydopamine Nanoformulation Prevents Retinal Neurodegeneration in a Preclinical Model of Diabetic Retinopathy

“…The drug loading was estimated using the high-performance liquid chromatography (HPLC, 1260 Infinity, Agilent, USA), and the encapsulation efficiency was calculated. The HPLC method for the detection of melatonin was adopted from previously reported articles . In that, utilized mobile phase was TFA/water/methanol 0.1:30:70 and ran on isocratic mode for 7 min.…”

“…The solution oxidation method was followed to synthesize polydopamine nanoparticles (PNPs) 16 and melatonin-loaded polydopamine nanoparticles (mPNPs). 18 Dopamine solution (1 mg/mL) only for the synthesis of polydopamine nanoparticles and dopamine solution (1 mg/mL) with melatonin (1:5, melatonin/dopamine w/w ratio) were prepared for the synthesis of mPNPs, and 0.1 N NaOH was added to the prepared solution in 1:8 molar ratio of NaOH/dopamine. The solution color turned to brown after continuous stirring at 750 rpm for 24 h at room temperature.…”

“…The HPLC method for the detection of melatonin was adopted from previously reported articles. 18 In that, utilized mobile phase was TFA/water/methanol 0.1:30:70 and ran on isocratic mode for 7 min. The peaks of melatonin were observed at Rt 3.6 and 5.2 min at wavelengths of 224 and 278 nm, respectively.…”

“…Polydopamine nanoparticles are also reported as biocompatible and ROS scavengers. − Besides that, dopamine deficiency is also reported in the progression of DR . Recently, melatonin-loaded nanoparticles have shown protective effects in the treatment of diabetic retinopathy by recovering the retinal inflammation. , Herein, we have developed melatonin-loaded polydopamine nanoparticles (mPNPs) in the development of DR treatment by restoring neural damage of the retina. We first studied the effect of rotenone on retinal neurodegeneration that leads to progress in diabetic-retinopathy-like conditions and demonstrated the nanotherapeutic option by restoring the retinal neurodegenerative damage in DR treatment.…”

Strategic Structural Control of Polyserotonin Nanoparticles and Their Application as pH-Responsive Nanomotors

“…In this study, anisotropic bowl-like mesoporous PST nanoparticles were elaborately fabricated by an interface-directed emulsion polymerization approach, inspired by the synthesis of polydopamine (PDA) [ 29 , 30 , 31 ]. The monomer, serotonin, was utilized alongside P123/F127/TMB, which formed stable composite micelles acting as nucleation sites.…”