Advanced Hydrogel-Based Drug Delivery System for Enhanced Neuroprotection in Traumatic Brain Injuries

The proposed project aims to develop a hydrogel-based drug delivery platform for traumatic brain injury (TBI), providing a safe and controlled release of neuroprotective drugs directly to the injured brain. Currently, there are no FDA-approved, field-capable solutions for managing open-head wounds or penetrating brain injuries. This research will address this critical gap by focusing on the following objectives:Formulation of In Situ Gelling Hydrogel Loaded with Glutathione and Minocycline: The project will develop in situ gelling hydrogels using chitosan, glycol chitosan, and collagen mixed with glycerophosphate. The hydrogels will be optimized for drug encapsulation efficiency and controlled release capabilities, ensuring compatibility with brain tissue.Formulation of Methylprednisolone-Loaded Solid Lipid Nanoparticles (SLPs): Methylprednisolone will be encapsulated in solid lipid nanoparticles using a melt-emulsification and ultrasonication method. The SLPs will be evaluated for particle size, distribution, morphology, encapsulation efficiency, and drug release kinetics.Design and Formulation of Functionalized SLPs for Cytosolic Delivery of Erythropoietin: Erythropoietin-loaded SLPs will be formulated with cell-penetrating peptides to enhance intracellular delivery. The SLPs will be optimized for size, shape, phase behavior, and cytocompatibility.Formulation of Microparticles Co-Loaded with Glutathione and Minocycline: Using an air atomization-assisted ionic complexation technique, microparticles co-loaded with glutathione and minocycline will be prepared. These microparticles will be evaluated for size, shape, phase behavior, encapsulation efficiency, and drug release kinetics.Preparation & Characterization of Microparticles Containing Drug-Loaded SLPs: Methylprednisolone-SLPs and Erythropoietin-SLPs will be co-encapsulated in microparticles. These will be characterized for size, shape, and encapsulation efficiency.Formulation of SLPs-in-Microparticles-in-Hydrogels Containing Drug Cocktails: The co-loaded microparticles will be incorporated into hydrogels. The multi-compartment hydrogel system will be characterized for viscosity, pH, conductivity, gelation time, viscoelasticity, drug content, and release rates.The Phase I effort will produce three primary deliverables:Comprehensive Report: Detailed documentation of the hydrogel formulation, characterization, and controlled release capabilities.Data Sets: Encapsulation efficiency, drug release profiles, stability data, and safety profiles.Prototype Hydrogel System: A working prototype of the multi-compartment hydrogel formulation with controlled release properties.This research will lay the groundwork for Phase II, which will involve pre-clinical in vivo studies to demonstrate safety, pharmacokinetics/pharmacodynamics (PK/PD), and therapeutic efficacy in established animal models of TBI. The successful completion of which will facilitate smooth progression to clinical phases.