Systemic Anti-Inflammatory Therapy Aided by Curcumin-Laden Double-Headed Nanoparticles Combined with Injectable Long-Acting Insulin in a Rodent Model of Diabetes Eye Disease

Therapeutic interventions that counter emerging targets in diabetes eye diseases are lacking. We hypothesize that a combination therapy targeting inflammation and hyperglycemia can prevent diabetic eye diseases. Here, we report a multipronged approach to prevent diabetic cataracts and retinopathy by...

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Published in:ACS nano 2023-04, Vol.17 (7), p.6857-6874
Main Authors: Ganugula, R., Arora, M., Dwivedi, S., Chandrashekar, D. S., Varambally, S., Scott, E. M., Kumar, M. N. V. Ravi
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - therapeutic use
Cataract - drug therapy
Curcumin - pharmacology
Curcumin - therapeutic use
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Experimental - pathology
Hyperglycemia - drug therapy
Insulin - therapeutic use
Insulin, Long-Acting - therapeutic use
Ion Channels
Mice
Nanoparticles
Retinal Diseases - drug therapy
Rodentia
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Summary:Therapeutic interventions that counter emerging targets in diabetes eye diseases are lacking. We hypothesize that a combination therapy targeting inflammation and hyperglycemia can prevent diabetic eye diseases. Here, we report a multipronged approach to prevent diabetic cataracts and retinopathy by combining orally bioavailable curcumin-laden double-headed (two molecules of gambogic acid conjugated to terminal carboxyl groups of poly­(d,l-lactide-co-glycolide)) nanoparticles and injectable basal insulin. The combination treatment led to a significant delay in the progression of diabetic cataracts and retinopathy, improving liver function and peripheral glucose homeostasis. We found a concurrent reduction in lens aggregate protein, AGEs, and increased mitochondrial ATP production. Importantly, inhibition of Piezo1 protected against hyperglycemia-induced retinal vascular damage suggesting possible involvement of Piezo1 in the regulation of retinal phototransduction. Histologic evaluation of murine small intestines revealed that chronic administration of curcumin-laden double-headed nanoparticles was well tolerated, circumventing the fear of nanoparticle toxicity. These findings establish the potential of anti-inflammatory and anti-hyperglycemic combination therapy for the prevention of diabetic cataracts and retinopathy.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.3c00535