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Systemic Anti-Inflammatory Therapy Aided by Curcumin-Laden Double-Headed Nanoparticles Combined with Injectable
R Ganugula1,2,3,4, M Arora1,2,3,4, S Dwivedi1,2
1The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, Alabama 35487, United States.
Abstract:
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.
Insights
A novel combination therapy using curcumin nanoparticles and basal insulin effectively delays diabetic cataracts and retinopathy. This approach targets inflammation and hyperglycemia, showing promise for preventing diabetes-related eye diseases.
Area of Science:
- Ophthalmology
- Endocrinology
- Nanomedicine
Background:
- Emerging targets for diabetic eye diseases lack effective therapeutic interventions.
- Diabetic cataracts and retinopathy pose significant challenges in diabetes management.
- Current treatments often fail to address both hyperglycemia and inflammation.
Purpose of the Study:
- To investigate a combination therapy for preventing diabetic cataracts and retinopathy.
- To evaluate the efficacy of orally administered curcumin nanoparticles combined with injectable basal insulin.
- To explore the underlying mechanisms, including Piezo1's role in retinal damage.
Main Methods:
- Developed orally bioavailable curcumin-laden double-headed nanoparticles.
- Administered nanoparticles in combination with injectable basal insulin.
- Assessed effects on diabetic cataracts, retinopathy, liver function, glucose homeostasis, and mitochondrial ATP production in vivo.
- Examined lens aggregate protein, advanced glycation end products (AGEs), and retinal vascular damage.
- Performed histologic evaluation of nanoparticle safety in murine small intestines.
Main Results:
- Combination therapy significantly delayed the progression of diabetic cataracts and retinopathy.
- Improved liver function and peripheral glucose homeostasis were observed.
- Reduced lens aggregate protein and AGEs, with increased mitochondrial ATP production.
- Inhibition of Piezo1 demonstrated protective effects against hyperglycemia-induced retinal vascular damage.
- Curcumin nanoparticles were well-tolerated, showing no signs of toxicity in murine models.
Conclusions:
- Combination therapy targeting inflammation and hyperglycemia shows potential for preventing diabetic eye diseases.
- This multipronged approach offers a promising strategy for managing diabetic complications.
- Further research into Piezo1's role may reveal new therapeutic avenues for retinal protection.
