Michela Abrami

Objectives: The physical stability of concentrated azelaic acid nanosuspensions cannot be predicted solely from interfacial stabilisation but reflects the interplay between particle size-dependent thermodynamic driving forces, polymer-mediated rheological structuring and the resulting bulk microstructural organisation. This study employed an A-optimal design of experiments (18 runs) to investigate formulation–process relationships in concentrated azelaic acid nanosuspensions (10–20% w/w) stabilised with a dual HPMC–chitosan system. Methods: Particle size, ζ-potential, rheological behaviour, solid-state properties and in vitro permeation across Strat-M® membranes were evaluated, and formulation–process relationships were analysed using multivariate modelling and logistic regression. Results: Particle size (342–1118 nm; R² = 0.97) was primarily governed by the applied milling regime. Logistic regression demonstrated a size-dependent probability of crystal growth, with the estimated particle-size transition point (predicted probability = 0.5) shifting from approximately 424 nm after preparation to 594 nm following accelerated storage at 40 °C. CHI concentration controlled ζ-potential (+18.5 to +47.9 mV), although ζ-potential alone did not adequately explain the observed storage stability. Where measurable, zero-shear viscosity (68–45,462 mPa·s) reflected substantial differences in low-shear rheological structuring, while formulations containing higher HPMC concentrations generally exhibited improved stability, consistent with polymer-mediated kinetic constraints on crystal growth. In vitro permeation studies using Strat-M^® membranes demonstrated permeation behaviour consistent with structured diffusion-controlled systems, exhibiting lower flux but more uniform permeation profiles than the reference formulation under the applied experimental conditions. Conclusions: Integration of multivariate modelling with rheological, solid-state and permeation characterisation provided an integrated understanding of the formulation–process relationships governing the short-term physical stability and comparative in vitro transport behaviour of concentrated dermal AZA nanosuspensions.

Patients with muco-obstructive lung disease (MOLD) exhibit chronic bronchitis and inflammation, along with a progressive decline in lung function. Lung monitoring is typically performed using spirometry, especially by measuring the forced expired volume in the first second (FEV₁). However, the limitations of spirometry motivated the exploration of alternative approaches. The spin–spin relaxation time (T_2m) and the spin–lattice relaxation time (T_1m) of sputum water hydrogens were measured using low-field nuclear magnetic resonance (LF-NMR) in 38 MOLD patients and 16 controls. The levels of TNFα/IL-6, the sputum microbiome composition/amount/indices and FEV₁ were determined in parallel. We also investigated the correlation between T_2m/T_1m and the disease index (I_D); I_D, calculated relying on patient FEV₁/TNFα/IL-6/bacteria concentration C_b values, is a measure of the patient’s distance from the average healthy control. We observed the following significant correlations: T_2m/T_1m with I_D, T_2m with C_b, a potential correlation of T_2m with the bacteria genera Streptococcus and Staphylococcus, T_2m with the Shannon index, which reflects the broadness of the bacterial community in the sputum, and T_2m with TNFα. FEV₁ did not show any correlation. Our noninvasive/radiation-free/portable method of T_2m/T_1m measurement shows potential value in monitoring lung conditions in MOLD patients and may contribute to improved clinical decision-making.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive respiratory disorder characterized by airflow limitation, chronic inflammation, and structural lung alterations. Despite advances in clinical monitoring, current approaches such as spirometry, symptom scores, and imaging remain limited in capturing disease complexity and early pathophysiological changes. In this context, microRNAs (miRNAs) have emerged as promising molecular biomarkers due to their involvement in key inflammatory and immune pathway regulation. Sputum is gaining attention as a non-invasive and informative matrix for studying COPD. As a surrogate of airway mucus, sputum reflects local pathological processes, including inflammation and tissue damage, and contains biomarkers such as miRNAs. Compared to circulating miRNAs, sputum-derived miRNAs appear to more accurately represent lung-specific alterations. In this review, we focus on works published so far about the identification of miRNAs in COPD sputum. Several miRNAs have been associated with COPD diagnosis, severity, and exacerbations. These findings, including the possible correlation of some miRNAs with sputum biophysical properties, support the value of integrated biomarker approaches. While further large-scale and standardized studies are required to validate the role of COPD miRNAs assessed in sputum, their evaluation in sputum represents a promising tool for improving the diagnosis, phenotyping and monitoring of COPD.

Background/Objectives: The present work proposes a mathematical model able to describe the dissolution of poly-disperse drug spherical particles in a solution (Dissolution Rate Test—DRT). DRT is a pivotal test performed in the pharmaceutical field to qualitatively assess drug bioavailability. Methods: The proposed mathematical model relies on the key hallmarks of DRT, such as particle size distribution, solubility, wettability, hydrodynamic conditions in the dissolving liquid of finite dimensions, and possible re-crystallization during the dissolution process. The spherical shape of the drug particles was the only cue simplification applied. Two model drugs were considered to check model robustness: theophylline (both soluble and wettable) and praziquantel (both poorly soluble and wettable). Results: The DRT data analysis within the proposed model allows us to understand that for theophylline, the main resistance to dissolution is due to the boundary layer surrounding drug particles, whereas wettability plays a negligible role. Conversely, the effect of low wettability cannot be neglected for praziquantel. These results are validated by the determination of drug wettability performed while measuring the solid–liquid contact angle on four liquids with decreasing polarities. Moreover, the percentage of drug polarity was determined. Conclusions: The proposed mathematical model confirms the importance of the different physical phenomena leading the dissolution of poly-disperse solid drug particles in a solution. Although a comprehensive mathematical model was proposed and applied, the DRT data of theophylline and praziquantel was successfully fitted by means of just two fitting parameters.

The respiratory mucus, a viscoelastic gel, effectuates a primary line of the airway defense when operated by the mucociliary clearance. In chronic respiratory diseases (CRDs), such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), the mucus is overproduced and its solid content augments, changing its structure and viscoelastic properties and determining a derangement of essential defense mechanisms against opportunistic microbial (virus and bacteria) pathogens. This ensues in damaging of the airways, leading to a vicious cycle of obstruction and infection responsible for the harsh clinical evolution of these CRDs. Here, we review the essential features of normal and pathological mucus (i.e., sputum in CF, COPD, and asthma), i.e., mucin content, structure (mesh size), micro/macro-rheology, pH, and osmotic pressure, ending with the awareness that sputum biomarkers (mucins, inflammatory proteins and peptides, and metabolites) might serve to indicate acute exacerbation and response to therapies. There are some indications that old and novel treatments may change the structure, viscoelastic properties, and biomarker content of sputum; however, a wealth of work is still needed to embrace these measures as correlates of disease severity in association with (or even as substitutes of) pulmonary functional tests.

Agarose is a natural polysaccharide known for its ability to form thermoreversible hydrogels. While the effects of curing temperature and polysaccharide concentration on mechanical properties have been discussed in the literature, the role of ionic strength has been less studied. In the present manuscript, we investigate the effects of supporting salt concentration and the role of cation (i.e. Na⁺ or Li⁺, neighbors in the Hofmeister series), on the setting and performance of agarose hydrogels. Compressive and rheological measurements show that the supporting salts reduce the immediate elastic response of agarose hydrogels, with Li⁺ showing a stronger effect than Na⁺ at high ionic strength, while they significantly increase the extent of linear stress-strain response (i.e., linear elasticity). The presence of increasing amounts of added supporting salt also leads to a reduction in hysteresis during mechanical deformation due to loading and unloading cycles, which is more pronounced with Li⁺ than with Na⁺. The combination of rheological measurements and NMR relaxometry shows a mesh size in agarose hydrogels in the order of 6–17 nm, with a thickness of the water layer bound to the biopolymer of about 3 nm. Of note, the different structuring of the water within the hydrogel network due to the different alkali seems to play a role for the final performance of the hydrogels.