The blood-brain barrier (BBB), a vital boundary between the neural tissue and circulating blood, is the homeostatic defense mechanism of the brain. Over 98% of therapeutic molecules have been unsuccessful in treating brain related diseases because these molecules or neurotherapeutic approaches cannot cross the BBB effectively. Therefore, it is important to investigate promising new approaches of delivering molecules to the brain that overcome these challenges. In this project, we will focus on therapy for neurodegenerative diseases (NDs) using mesoporous silica nanoparticles (MSN). To be considered a viable option for NDs therapy, MSN must be small, stable in blood circulation, not induce reactive oxygen species (ROS) or inflammation, have low neurotoxicity, and escape the clearance of the reticuloendothelial system (RES). This project aims to develop more biocompatible MSN to achieve the above properties through modifications in size, charge, and PEGylation. Hence, PEGylated MSN with different positive charges and two different diameters (50 and 200 nm) will be prepared and characterized first, and then the cell response related studies will be investigated in vitro. Subsequently, various pharmacokinetic, pharmacodynamic and biodistribution studies in vivo will be carried out to identify which MSNs are the most biocompatible. Developing therapeutic MSN to induce neurogenesis could be a promising therapeutic approach in these NDs through the endogenous regenerative capacity of brain. In aim 2 of this project, strategies for antioxidant therapy, gene delivery therapy and a combination of antioxidant-gene delivery therapy, using biocompatible PEGylated MSN, will be demonstrated. We propose that combination therapy based on MSN, instead of single drug treatment, will be emerging as an attractive strategy which is beneficial to maximize the therapeutic effect with minimized side effects for NDs. Most importantly, in vivo studies on the transport of PEGylated MSN across the BBB will also be evaluated.
|Effective start/end date||1/1/18 → 7/31/18|
- Mesoporous Silica Nanoparticles (MSN)
- Neurodegenerative Diseases (NDs)
- Blood-Brain Barrier (BBB)
- Reticuloendothelial System (RES)
- Combination Therapy
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