Evidence of Strong Guest-Host Interactions in Simvastatin Loaded in Mesoporous Silica MCM-41.

A rational design of drug delivery systems requires in-depth knowledge not only of the drug itself, in terms of physical state and molecular mobility, but also of how it is distributed among a carrier and its interactions with the host matrix. In this context, this work reports the behavior of simvastatin (SIM) loaded in mesoporous silica MCM-41 matrix (average pore diameter ~3.5 nm) accessed by a set of experimental techniques, evidencing that it exists in an amorphous state (X-ray diffraction, ssNMR, ATR-FTIR, and DSC). The most significant fraction of SIM molecules corresponds to a high thermal resistant population, as shown by thermogravimetry, and which interacts strongly with the MCM silanol groups, as revealed by ATR-FTIR analysis. These findings are supported by Molecular Dynamics (MD) simulations predicting that SIM molecules anchor to the inner pore wall through multiple hydrogen bonds. This anchored molecular fraction lacks a calorimetric and dielectric signature corresponding to a dynamically rigid population. Furthermore, differential scanning calorimetry showed a weak glass transition that is shifted to lower temperatures compared to bulk amorphous SIM. This accelerated molecular population is coherent with an in-pore fraction of molecules distinct from bulklike SIM, as highlighted by MD simulations. MCM-41 loading proved to be a suitable strategy for a long-term stabilization (at least three years) of simvastatin in the amorphous form, whose unanchored population releases at a much higher rate compared to the crystalline drug dissolution. Oppositely, the surface-attached molecules are kept entrapped inside pores even after long-term release assays.

Relationship Between the Self-Concept of Children and Their Ability to Recognize Emotions in Others.

The aim of this study was to assess the relationship between the self-concept of children and their ability to recognize emotions in others from facial expressions. It is hypothesized that children use their self-representations to interpret depictions of emotion in others and that higher self-concepts might be associated with earlier development of emotion recognition skills. A total of 54 children aged between 5 and 11 years participated in this study. Self-concept was assessed in all children using the Piers-Harris Self-Concept Scale for Children (Piers-Harris 2). To assess emotion recognition, a computerized instrument, the Penn Emotion Recognition Task (PERT), was applied. Despite the small sample of children, results show clear statistical effects. It is shown that emotion recognition ability is directly correlated with self-concept for intellectual/school status. The ability to correctly identify emotions from facial expressions is affected by general self-concept, intellectual/school status, and stimulus features of gender, intensity, and emotion. Further analysis shows that the general self-concept of children particularly affects the ability to identify happy faces. Children with a higher intellectual status score recognize happiness and neutral faces more easily. We concluded that the self-concept in children relates to the ability to recognize emotions in others, particularly positive emotions. These findings provide some support to the simulation theory of social cognition, where children use their own self-representations to interpret mental states in others. The effect of the self-concept for intellectual status on emotion recognition might also indicate that intellectual abilities act as a mediator between self-concept and emotion recognition, but further studies are needed.

How Molecular Mobility, Physical State, and Drug Distribution Influence the Naproxen Release Profile from Different Mesoporous Silica Matrices.

Aiming to evaluate how the release profile of naproxen (nap) is influenced by its physical state, molecular mobility, and distribution in the host, this pharmaceutical drug was loaded in three different mesoporous silicas differing in their architecture and surface composition. Unmodified and partially silylated MCM-41 matrices, respectively MCM-41 and MCM-41sil, and a biphenylene-bridged periodic mesoporous organic matrix, PMOBph, were synthetized and used as drug carriers, having comparable pore sizes (∼3 nm) and loading percentages (∼30% w/w). The loaded guest was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dielectric relaxation spectroscopy (DRS). DSC and XRD confirmed amorphization of a nap fraction incorporated inside the pores. A narrower glass transition was detected for PMOBph_nap, taken as an indication of the impact of host ordering, which also hinders the guest molecular mobility inside the pores as probed by DRS. While the PMOBph matrix is highly hydrophobic, the unmodified MCM-41 readily adsorbs water, accelerating the nap relaxation rate in the respective composite. In the dehydrated state, the faster dynamics was found for the silylated matrix since guest-host hydrogen bond interactions were inhibited to some extent by methylation. Nevertheless, in all the prepared composites, bulk-like crystalline drug deposits outside pores in a greater extent in PMOBph_nap. The DRS measurements analyzed in terms of conductivity show that, upon melting, nap easily migrates into pores in MCM-41-based composites, while it stays in the outer surface in the ordered PMOBph, determining a faster nap delivery from the latter matrix. On the other side, the mobility enhancement in the hydrated state controls the drug delivery in the unmodified MCM-41 matrix vs the silylated one. Therefore, DRS proved to be a suitable technique to disclose the influence of the ordering of the host surface and its chemical modification on the guest behavior, and, through conductivity depletion, it provides a mean to monitor the guest entrance inside the pores, easily followed even by untrained spectroscopists.

Stabilizing Unstable Amorphous Menthol through Inclusion in Mesoporous Silica Hosts.

The amorphization of the readily crystallizable therapeutic ingredient and food additive, menthol, was successfully achieved by inclusion of neat menthol in mesoporous silica matrixes of 3.2 and 5.9 nm size pores. Menthol amorphization was confirmed by the calorimetric detection of a glass transition. The respective glass transition temperature, Tg = -54.3 °C, is in good agreement with the one predicted by the composition dependence of the Tg values determined for menthol:flurbiprofen therapeutic deep eutectic solvents (THEDESs). Nonisothermal crystallization was never observed for neat menthol loaded into silica hosts, which can indicate that menthol rests as a full amorphous/supercooled material inside the pores of the silica matrixes. Menthol mobility was probed by dielectric relaxation spectroscopy, which allowed to identify two relaxation processes in both pore sizes: a faster one associated with mobility of neat-like menthol molecules (α-process), and a slower, dominant one due to the hindered mobility of menthol molecules adsorbed at the inner pore walls (S-process). The fraction of molecular population governing the α-process is greater in the higher (5.9 nm) pore size matrix, although in both cases the S-process is more intense than the α-process. A dielectric glass transition temperature was estimated for each α (Tg,dielc(α)) and S (Tg,dielc(S)) molecular population from the temperature dependence of the relaxation times to 100 s. While Tg,dielc(α) agrees better with the value obtained from the linearization of the Fox equation assuming ideal behavior of the menthol:flurbiprofen THEDES, Tg,dielc(S) is close to the value determined by calorimetry for the silica composites due to a dominance of the adsorbed population inside the pores. Nevertheless, the greater fraction of more mobile bulk-like molecules in the 5.9 nm pore size matrix seems to determine the faster drug release at initial times relative to the 3.2 nm composite. However, the latter inhibits crystallization inside pores since its dimensions are inferior to menthol critical size for nucleation. This points to a suitability of these composites as drug delivery systems in which the drug release profile can be controlled by tuning the host pore size.

Transoral robotic retropharyngeal node dissection.

BACKGROUND: Surgical access to metastases in the retropharyngeal lymph nodes (RPLNs) could be difficult. Transoral robotic surgery (TORS) can be utilized to access RPLNs. The purpose of this study was to describe a TORS approach to RPLN dissection. METHODS: A case series of patients undergoing RPLN dissection by TORS was conducted and compared to matched controls (1:2). RESULTS: Twelve patients underwent robotic RPLN dissection. Median age was 63 years (range, 43-73 years). Pathology was oropharyngeal squamous cell carcinoma (SCC) in 9 patients and papillary thyroid cancer (PTC) in 3 patients. The feeding tube dependence duration was 12 days (range, 1-46 days) on average. Complications occurred in 8 patients (66%); most commonly, aspiration pneumonitis in 6 patients. In comparison to the matched controls (24), there was no difference in length of stay or feeding tube dependence. Complications were higher in patients with oropharyngeal SCC. CONCLUSION: TORS is feasible for accessing RPLNs. The procedure is well tolerated in patients with PTC; whereas patients with oropharyngeal SCC are at increased risk of complications. © 2015 Wiley Periodicals, Inc. Head Neck 38: E981-E986, 2016.