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.

Recovery of phenolic compounds from multi-component solution by a synthesized activated carbon using resorcinol and formaldehyde.

The adsorption of four phenolic compounds (gallic acid, protocatechuic acid, vanillic acid and syringic acid) is investigated using a synthesized mesoporous carbon on both single and multi-component synthetic solutions. Some correlation of the adsorption capacity of the carbon and the nature of adsorbate could be made, except for gallic acid whose concentration decrease seems to be not exclusively due to adsorption but also to polymerization reaction. In the multi-component mixture, negative effects in the adsorption capacity are observed probably due to competition for the active centers of the adsorbent surface. In desorption studies, ethanol presents better performance than water and acetonitrile. Vanillic acid is the compound with the higher adsorption and interestingly it is then possible to desorb a relatively high amount of it from the adsorbent, which may represent a possibility for a selective recovery of vanillic acid. These results present a potential way to treat the wastewater from the cork industry.

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.

Health-related quality of life may improve after transplantation in pancreas-kidney recipients.

Pancreas-kidney transplantation (PKT) may significantly improve quality of life (HRQOL) in patients with type 1 diabetes. We have assessed the changes felt by PKT patients, using the Gastrointestinal Quality of Life Index (GIQLI) and EuroQol-5D questionnaires. Patients were asked to compare how their HRQOL had changed from pre-transplantation to the last visit. The 60 men and 66 women enrolled had a mean follow-up of five yr; 84.1% with both grafts, 15.9% with one graft functioning. In all domains of EuroQol-5D scores improved after PKT, as well as the visual analogue scale health state (from 38% to 84%, p < 0.001; effect size 3.34). In GIQLI, physical function was felt better after PKT than before (14.83 ± 3.86 vs. 7.86 ± 4.43, p < 0.001; effect size 1.68); the same was observed for psychological status, social function, and GI complaints. Concerning the burden of medical treatment, the score significantly improved (from 1.31 to 3.63, p < 0.001, effect size 2.02). The rate of unemployed patients decreased after PKT (from 50.8% to 36.5%, p < 0.001). Multivariate analysis showed that having only one functioning graft was associated with worse HRQOL scores (B = -5.157, p = 0.015). In conclusion, for all assessed domains, patients reported a significant improvement in HRQOL after PKT. Maintenance of the two grafts functioning predicted higher improvement of HRQOL scores.

Pancreatic autoantibodies after pancreas-kidney transplantation - do they matter?

Type 1 diabetes recurrence has been documented in simultaneous pancreas-kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow-up (maximum 138 months), 43.8% of patients were positive (from pre-transplant or after recurrence) for at least one autoantibody - the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti-insulin (8.6%) and anti-islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C-peptide levels, and a higher number of HLA-matches. Analyzing the sample divided into four groups according to pre-/post-transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C-peptide levels. Positivity for these autoantibodies pre-transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody-positive SPKT is a matter of concern, which deserves further attention.

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.

WO3 nanoparticle-based conformable pH sensor.

pH is a vital physiological parameter that can be used for disease diagnosis and treatment as well as in monitoring other biological processes. Metal/metal oxide based pH sensors have several advantages regarding their reliability, miniaturization, and cost-effectiveness, which are critical characteristics for in vivo applications. In this work, WO3 nanoparticles were electrodeposited on flexible substrates over metal electrodes with a sensing area of 1 mm(2). These sensors show a sensitivity of -56.7 ± 1.3 mV/pH, in a wide pH range of 9 to 5. A proof of concept is also demonstrated using a flexible reference electrode in solid electrolyte with a curved surface. A good balance between the performance parameters (sensitivity), the production costs, and simplicity of the sensors was accomplished, as required for wearable biomedical devices.

Activated carbons from sisal waste by chemical activation with K2CO3: kinetics of paracetamol and ibuprofen removal from aqueous solution.

Sisal waste was used as precursor to prepare carbons by chemical activation. The influence of the K(2)CO(3) amount and activation temperature on the materials textural properties were studied through N(2) and CO(2) adsorption assays. As the severity of the treatment increases there is a development of supermicropores, and the micropore size distribution changes from mono to bimodal. A carbon with an apparent surface area of 1,038 m(2)g(-1) and pore volume of 0.49 cm(3)g(-1) was obtained. TPD results showed the incidence in acidic type groups although the pH(PZC) reveals an almost neutral character of the surface. Adsorption kinetic data of ibuprofen and paracetamol show that the processes obey to a pseudo-second order kinetic equation. Regarding the removal efficiency the prepared samples attained values comparable to a commercial carbon (>65%), revealing that chemical activation of sisal wastes with K(2)CO(3) allows obtaining samples suitable for pharmaceutical compounds removal from liquid phase.

Survey of infectious and parasitic diseases in stray cats at the Lisbon Metropolitan Area, Portugal.

A survey of infectious and parasitic diseases of stray cats was carried out using biological samples collected from animals captured during a catch-neuter-release programme in four counties of the Lisbon Metropolitan Area. The main objective was to investigate the potential threat of stray cats for animal and public health. Samples of blood, stool, hair and auricular swabs were collected from 231 cats in 27 colonies. Anti-Toxoplasma gondii antibodies were detected in 47/194 samples (24.2%); anti-Leishmania infantum antibodies in 1/180 cats (0.6%); intestinal parasites in 23/74 samples (Toxocara cati, Isospora felis, Ancylostoma tubaeforme, Dipylidium caninum, Uncinaria stenocephala, Toxascaris leonina) and Otodectes cynotis in 4/182 cats (2.2%); dermatophyte fungi were isolated in 40/136 samples (29.4%); feline immunodeficiency virus antibodies were detected in 23/226 samples (10.2%); feline leukaemia virus antigen in 14/198 samples (7.1%); and feline coronavirus RNA in 9/127 samples (7.1%). Our results revealed that zoonotic agents, namely dermatophyte fungi and Toxocara cati were present in stray cat colonies in the investigated counties. Overall the low frequency of major pathogens suggests a balanced relationship between host and agents.