We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP_−3.11, CHP_−6.03, CHP_−6.91 and CHCP_−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge.

Background: Parkinson’s disease (PD) involves both regional cortical degeneration and large-scale network dysfunction. This study examined whether cortical regions showing structural abnormalities in PD also exhibit altered directed connectivity. Methods: Sixty-two patients with PD and 46 healthy controls underwent structural magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (fMRI). Whole-brain cortical thickness was analyzed using FreeSurfer. Regions showing significant cortical thinning were used as seeds for voxel-wise Granger causality analysis (GCA). Associations between imaging measures and Montreal Cognitive Assessment (MoCA) scores were examined using partial correlation analyses. Results: Patients with PD showed significantly reduced cortical thickness in the right medial superior frontal gyrus (SFGmed.R) and right precentral gyrus (PreCG.R), with no regions showing significantly greater cortical thickness than healthy controls. Compared with controls, patients with PD exhibited increased GCA from SFGmed.R to the left inferior temporal gyrus and from PreCG.R to the calcarine/medial visual cortex, whereas decreased GCA was observed from PreCG.R to the left supramarginal gyrus and from the right superior temporal gyrus and left olfactory-related region to PreCG.R. SFGmed.R cortical thickness was positively associated with MoCA scores after adjustment for age, sex, and education level, and this association remained significant after Bonferroni correction for seven exploratory correlation analyses (partial Spearman’s ρ = 0.847, p < 0.001). No other imaging–MoCA associations reached the corrected significance threshold. Conclusion: Cortical thinning in frontal-executive and motor regions of patients with PD is accompanied by altered directed interactions with distributed sensory and associative regions. Medial superior frontal cortical thickness may also be related to global cognitive performance.