ABSTRACT
OBJECTIVE: Traumatic brain injury (TBI) is a serious health problem with few available treatment options. Rh-erythropoietin (rh-EPO) is a potential therapeutic drug for TBI, but it cannot cross the blood-brain barrier (BBB) directly. In this regard, a novel strategy to deliver rh-EPO for enhanced TBI treatment is via the development of Tween 80 modified albumin nanoparticles using electrostatic spray technology. METHODS: The rh-EPO loaded Tween 80 modified albumin nanoparticles (rh-EPO-Tw-ABNPs) were prepared by electrostatic spray technology, while the process parameters were optimized via a single factor design. Investigation of physicochemical properties, bioactivity and stability of rh-EPO-Tw-ABNPs was carried out. The in vitro release and biocompatibility with nerve cells were also analyzed. The in vivo brain targeting efficiency, brain edema relieving effect and the expression of aquaporin 4 (AQP4) and glial fibrillary acidic protein (GFAP) in the brain were evaluated in TBI model rats. RESULTS: The particle size of optimal rh-EPO-Tw-ABNPs was about 438 ± 45 nm, with a zeta potential of -25.42 ± 0.8 mv. The average drug loading ratio of rh-EPO-Tw-ABNPs was 21.3± 3.7 IU/mg with a relative bioactivity of 91.6 ± 4.1%. The in vitro release of rh-EPO from the nanoparticles was rather slow, while neither the blank Tw-ABNPs nor rh-EPO-Tw-ABNPs exhibited toxicity on the microglia cells. Furthermore, in vivo experiments indicated that the rh-EPO-Tw-ABNPs could enhance the distribution of EPO in the brain and relieve brain edema more effectively. Moreover, compared with an rh-EPO injection, the rh-EPO-Tw-ABNPs could increase the AQP4 level but reduced GFAP expression in the brain with more efficiency. CONCLUSION: The rh-EPO-Tw-ABNPs could enhance the transport of rh-EPO into the brain with superior therapeutic effect for TBI.
Subject(s)
Albumins/chemistry , Brain Injuries, Traumatic/drug therapy , Erythropoietin/therapeutic use , Nanoparticles/chemistry , Recombinant Proteins/therapeutic use , Animals , Aquaporin 4/metabolism , Brain/drug effects , Brain/pathology , Brain Edema/drug therapy , Drug Liberation , Erythropoietin/pharmacology , Glial Fibrillary Acidic Protein/metabolism , Humans , Male , Nanoparticles/ultrastructure , Neurons/pathology , Particle Size , Rats, Sprague-Dawley , Recombinant Proteins/pharmacology , Rheology , Static ElectricityABSTRACT
OBJECTIVE: To analyze the significance of intracranial pressure (ICP)-related parameters on outcome in patients with severe traumatic brain injury. The ICP-related parameters included ICP, ICP dose (DICP), regression of the correlation coefficient between amplitude and pressure (RAP), pressure reactivity index (PRx), and cerebral perfusion pressure (CPP). METHODS: A retrospective analysis was performed using clinical information from 29 patients with severe traumatic brain injury who were admitted to the Department of Neurosurgery from January 2018 to January 2019. All patients underwent ICP probe implantation after admission. Patients were followed up for 6 months after discharge, and were categorized into either the favorable or unfavorable outcome group based on their Glasgow Outcome Scale score. The differences in ICP, DICP, RAP, PRx, and CPP between the two groups were analyzed for their effects on outcome. RESULTS: The average ICP, DICP, PRx, and RAP values in patients with favorable outcomes were significantly lower than in patients with unfavorable outcomes, while CPP values were significantly higher in the favorable outcome group. CONCLUSION: Average ICP, DICP, PRx, RAP, and CPP values may indicate disease status and relate to patient outcomes. It is important to use multiple parameters to predict patients' disease severity and prognosis.
Subject(s)
Brain Injuries, Traumatic , Intracranial Pressure , Brain Injuries, Traumatic/diagnosis , Cerebrovascular Circulation , Glasgow Outcome Scale , Humans , Retrospective Studies , Treatment OutcomeABSTRACT
A mild and clean liquid nitration of benzene with 65% nitric acid as nitrating agent over silica supported ammonium salt of 12-molybdophosphoric acid catalysts has been investigated. These catalysts with different loadings were prepared by sol-gel method and characterized by X-ray diffraction (XRD) and FTIR spectra. The acidity of these catalysts was measured by the potentiometric titration method. The XRD and IR analysis revealed that supported catalysts possess the Keggin structure which is similar to 12-molybdophosphoric acid. And it can be found that the supported catalysts had high nitration reaction catalytic activity and selectivity over nitrobenzene. The effects of various parameters such as nitric acid/benzene volume ratio, temperature and time of reaction have also been systematically studied.
