Glucose-Sensitive Delivery of Vitamin K by Using Surface-Functionalized, Dextran-Capped Mesoporous Silica Nanoparticles To Alleviate Hyperglycemia
Sanjib Sarkar, Pritam Sadhukhan, Dibyendu Das, Purashri Basyach, Joydeep Das, Manash R. Das, Lakshi Saikia, Sawlang Borsingh Wann, Jatin Kalita, Parames C. Sil, Prasenjit Manna
Abstract
Glucose-responsive delivery of antidiabetic molecules is gaining scientific attention as one of the promising strategies for maintaining normoglycemia and reducing the risk of overdose associated with the molecule. However, the water-insoluble antidiabetic molecules are not studied yet to deliver in a glucose-sensitive way. Herein, we examined the glucose-responsive delivery of vitamin K (VK) by using dextran-capped mesoporous silica nanoparticles (MSNs) functionalized with 3-carboxyphenylboronic acid (CPBA). The VK was loaded inside the pores of MSN-CPBA by physical adsorption, and the loading capacity of MSN-CPBA was 206.7 μg/mg (w/w). The pores of the nanoparticles were capped by using dextran via binding with CPBA, and the dextran-caps were untethered in the presence of glucose by competing with dextran to CPBA allowing the release of VK. The release of VK was 19.48 μg/mL in a cell-free system and 1.5 and 0.99 μg/mL in muscle and liver cells, respectively, in exposure to 25 mM glucose. The system not only delivered the VK in a glucose-dependent manner but also significantly improved the bioavailability thereof. The finding showed the promising therapeutic potential of MSN-CPBA-VK-Dex in reducing hyperglycemia in both in vitro and in vivo systems. The MSN-CPBA-based dextran-gated delivery system would be a promising therapeutic strategy to increase the bioavailability and stimuli-responsive delivery of antidiabetic molecules for managing diabetes mellitus over conventional approaches.