ABSTRACT
Objective: To establish a vitamin K1(VK1)-delivery system with red blood cells as carrier. Methods: The VK1 self-emulsifying nano-emulsion, micelle and plasma solution were prepared to investigate the VK1 loading on red blood cells. The VK1- chitosan(CS)nanoparticles were prepared with different particle size by the 3 different preparation methods, and the effect of the particle size and charge property on the VK1-loading on red blood cells was investigated with the prepared VK1-CS nanoparticles. The encapsulation efficiency and drug loading were used as main indicators to investigate the appropriate drug loading method. Results: Due to the solubility of VK1 or the charge properties of nanoparticles, the drug loading and encapsulation efficiency of the red blood cell-encapsulated VK1 were quite low, and a large amount of drugs could not be loaded on the red blood cells. The ability of red blood cells to load VK1 was likely related to its Zeta potential. The VK1-CS nanoparticles prepared by the ion condensation method showed a good drug loading performance. Each milliliter of red blood cells could load 174.46 μg VK1 in the nanoparticles, and the loading rate was 85.11%. Conclusion: The VK1 loading by the red blood cells could be achieved by the electrostatic interaction between the positively charged chitosan nanoparticles and the negatively charged erythrocyte membrane.
ABSTRACT
<p><b>BACKGROUND</b>Neuroimaging studies have found that functional changes exist in patients with Parkinson's disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.</p><p><b>METHODS</b>Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.</p><p><b>RESULTS</b>Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).</p><p><b>CONCLUSIONS</b>The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease's progression in patients with PD.</p>