Delivery of Tempol from Polyurethane Nanocapsules to Address Oxidative Stress Post-Injury

Abstract

Traumatic brain injuries (TBIs) result in significant morbidity and mortality due to the cascade of secondary injuries involving oxidative stress and neuroinflammation. The development of effective therapeutic strategies to mitigate these effects is critical. This study explores the fabrication and characterization of polyurethane nanocapsules for the sustained delivery of Tempol, a potent antioxidant. The nanocapsules were designed to extend the release of Tempol over a 30-day period, addressing the prolonged oxidative stress observed post-TBI. Tempol-loaded polyurethane nanocapsules were synthesized using interfacial polymerization and nanoemulsion techniques. Two generations of nanocapsules were produced, differing in Tempol loading and PEGylation levels. The first generation, with lower Tempol loading, exhibited an average size of 159.8 ± 12.61 nm and a Z-average diameter of 771.9 ± 87.95 nm. The second generation, with higher Tempol loading, showed an average size of 141.4 ± 6.13 nm and a Z-average diameter of 560.7 ± 171.1 nm. The zeta potentials were -18.9 ± 5.02 mV and -11.9 ± 3.54 mV for the first and second generations, respectively. Both generations demonstrated the presence of urethane linkages, confirmed by Fourier Transform Infrared Spectroscopy (FTIR). Loading studies revealed Tempol concentrations of 61.94 ± 3.04 μg/mg for the first generation and 77.61 ± 3.04 μg/mg for the second generation nanocapsules. Release profiles indicated an initial burst followed by a sustained, nearly linear release over 30 days. The higher PEGylation in the second generation nanocapsules is advantageous for intravenous administration, potentially enhancing their therapeutic efficacy in TBI treatment. This study demonstrates the feasibility of using polyurethane nanocapsules for the prolonged delivery of Tempol, offering a promising approach to manage oxidative stress and improve outcomes in TBI patients. Future work will include testing these nanocapsules in vivo to determine their potential at modulating recovery from TBI.