UC San Diego

Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. The overall goal of this research is to develop as nanoparticle capable of sustained drug release for the delivery and treatment of TBI so that therapeutic drug can be delivered after the Blood Brain Barrier (BBB) closes 24 hours after injury. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles have shown some experimental success; as of yet, none have yielded improved results of clinical efficacy. Polyethylene Glycol (PEG) has been shown to act as a stealth molecule that can increase the circulation time of particles. N-acetylcysteine has shown neuroprotective and anti-inflammatory potential. This paper presents the development of PEGylated PLGA NPs synthesized using double and single emulsion for potential therapeutic delivery to TBI. Dynamic light scattering (DLS) show PEG-PLGA NPs to have an average diameter of 200 nm. Loading capacity was obtained at 2%, and drug encapsulation efficiency was obtained at 55%. A biphasic drug release pattern was noted in situ and drug release was assessed in vitro over 72 h using FRET nanoparticles, almost complete release of drug was seen during this time period. Finally, in vivo administration of PEG-PLGA NPs demonstrated that PEGylated NPS were able to show reduced accumulation in filtration organs such as the liver and kidneys compared to bare PLGA particles. This evidence supports the potential of PEG-PLGA NPs as a promising carrier to develop TBI therapeutics.