Investigating molecular interactions of high-loaded glipizide-HPMCAS microparticles by integrated experimental and modeling techniques.

Molecular interactions between drug and polymeric carriers are believed to be the key for high drug loading and better physical stability of micro-particles. However, molecular interactions between drug and polymer are still difficult to investigate using only experimental tools. In this study, high-loaded glipizide (GLP)/hydroxypropyl methylcellulose acetate succinate (HPMCAS) (1/1 w/w) micro-particles were prepared using an in situ pH-dependent solubility method. Molecular interactions within the micro-particles were investigated by integrated experimental and modeling techniques. The dissolution rate of GLP/HPMCAS micro-particles was significantly better than those of solid dispersions and physical mixtures. Scanning electron microscopy images showed that the polymer inhibited GLP recrystallization. Experimental (FTIR spectroscopy, differential scanning calorimetry, powder X-ray diffraction and nuclear magnetic resonance spectroscopy) and molecular dynamics simulation revealed that hydrogen-bonding was the key to the properties of the micro-particles. Our research developed high drug-loading GLP/HPMCAS micro-particles and investigated the interactions between drug and polymer at the molecular level. This integrated approach could be practical methodology for future formulation design.

The resilient brain: psychological resilience mediates the effect of amplitude of low-frequency fluctuations in orbitofrontal cortex on subjective well-being in young healthy adults.

Psychological resilience reflects the capacity to bounce back from stress, which plays an important role in health and well-being. However, less is known about the neural substrate for psychological resilience and the underlying mechanism for how psychological resilience enhances subjective well-being in the healthy brain. To investigate these issues, we employed fractional amplitude of low-frequency fluctuations (fALFF) measured with resting-state fMRI in 100 young healthy adults. The correlation analysis found that higher psychological resilience was related to lower fALFF in the left orbitofrontal cortex (OFC), which is involved in reward-related processing and emotion regulation. Furthermore, the mediation analysis indicated that psychological resilience acted as a full mediator of the association between the fALFF in left OFC and subjective well-being indicators (i.e. life satisfaction and hedonic balance). Importantly, these results remained significant after controlling for the effect of gray matter volume and regional homogeneity in the region. Overall, the present study provides the further evidence for functional neural substrates of psychological resilience and reveals a potential mechanism that psychological resilience mediates the effect of spontaneous brain activity on subjective well-being.