Executive Summary : | The PI and Co-PIs have developed a novel drug complex, MIL 88B, for the sustained release of an ophthalmic drug, Timolol, based on their expertise in Metal Organic Framework (MOF) synthesis. The Co-PI found that Lithium (Li+) plays a significant role in the survival and regeneration of retinal ganglion cells, which are suitable for treating glutamate toxicity causing retinal neural degeneration in incurable ocular diseases like Glaucoma and Diabetic retinopathy leading to blindness. To circumvent Li+ toxicity, the researchers synthesized a novel drug complex comprising lithium, Coenzyme Q, and Vitamin E, which attenuate neural degeneration and can be used as auxiliary substituents with medicine. Lithium upregulates the Bcl-2 gene, releasing Bcl-2 neuroprotective protein and increasing glutamate uptake, which regulates signal transduction intermediates for antiapoptotic pathways. Lithium demonstrates robust neuroprotective effects against bipolar disorders and is the only medicine to significantly increase Bc1-2 levels.
The proposed drug complex will be loaded in a 3D porous biocompatible, non-toxic, and mucoadhesive MOF for sustained release. The drug cargo will be conjugated to a homo-pentameric and non-toxic protein, anti-inflammatory Cholera toxin B(CTB), to target the monosialotetrahexosylganglioside (GM1) protein on the RGC surface for internalization. The in-vivo therapeutic efficacy of the drug assembly will be assessed by bioavailability analysis in the NMDA-induced Wistar rat model. The proposed targeted, sustained release drug assembly is a perfect combination with existing drugs for the prevention and control of retinal ganglion cell degeneration and has strong viability for practical application to save ocular patients from blindness. |
Co-PI: | Dr. Madhumita p Ghosh, Amity University, Noida, Uttar pradesh-201313, Dr. Chansi, Amity University, Noida, Uttar pradesh-201313 |