Alleviation of Diabetic Retinopathy by Glucose-Triggered Delivery of Vitamin D via Dextran-Gated Functionalized Mesoporous Silica Nanoparticles

• Published in: ACS applied bio materials 2024-02, Vol.7 (2), p.1260-1270
• Main Authors: Sarkar, Sanjib, Osman, Narin, Thrimawithana, Thilini, Wann, Sawlang Borsingh, Kalita, Jatin, Manna, Prasenjit
• Format: Article
• Language: English
• Subjects: Dextrans; Diabetes Mellitus; Diabetic Retinopathy - drug therapy; Glucose; Humans; Inflammation; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Silicon Dioxide - chemistry; Vitamin D - therapeutic use
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.3c01200

Diabetic retinopathy (DR) is the most common retinal disorder, developed in 35% of patients with diabetes mellitus. Lower serum levels of 25-hydroxyvitamin D are associated with the increased risk of developing DR. High doses of the active form of vitamin D (VD), on the contrary, for a long period of time may lead to hypercalcemia and an imbalance in the regulation of bone metabolism. Herein, we studied the efficacy of dextran-gated carboxyphenylboronic acid (CPBA)-functionalized mesoporous silica nanoparticles (MSNs) for glucose-sensitive delivery of 1,25-dihydroxyvitamin D3 to modulate cellular oxidative stress and inflammation for managing DR. The physical adsorption technique was employed to load VD onto nanoparticles (263.63 μg/mg (w/w)). In the presence of glucose, the dextran molecules detach from pores, allowing VD to release since glucose has 1,2-cis diol groups which have very high affinity to CPBA. Approximately 75% of VD was released upon exposure to 25 mM glucose at a time point of 10 h, demonstrating glucose-responsive delivery. Furthermore, MSN-CPBA was able to deliver VD in a glucose-dependent manner and improve the bioavailability of VD. In high-glucose-supplemented human retinal cells, MSN-CPBA increased the bioavailability of VD and reduced cellular oxidative stress and inflammation. The results suggested that the VD-loaded nanocarrier exerted remarkable therapeutic capacity in reducing the risk of developing DR. By using MSN-CPBA as a delivery platform with dextran gating, the research proposes an effective treatment approach for improving the bioavailability and effectiveness of a hydrophobic molecule in the treatment of DR.