Elective affinities

We propose a marriage model where assortative matching results in equilibrium for reasons other than those driving similar results in the search and matching literature. A marriage is a joint venture where husband and wife contribute to the couple’s welfare by allocating their time to portfolios of risky activities. Men and women are characterised by different preferences over risk and the optimal match is between partners with the same level of risk aversion. In our model no two men (women) rank the same woman (men) as most desirable. Given that there is no unanimous ranking of candidates, everyone marries in equilibrium their most preferred partne

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin-drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus-PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin-drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption

Towards a better mechanistic comprehension of drug permeation and absorption: Introducing the diffusion-partitioning interplay

The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad (R) plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption. The effect of diffusion/permeability media composition and viscosity on the apparent permeation resistance (R-app) of model drugs caffeine (CAF) and hydrocortisone (HC) were tested and evaluated by varying the type and concentration of viscosity-enhancing agent - glycerol or a poly(ethylene glycol) (PEG) with different average molecular weights. For all types of media, increased viscosity lead to reduction in diffusivity but could not alone explain the observed effect, which was attributed to intermolecular polymer-drug interactions. Additionally, for both drugs, smaller hydrophilic viscosity-enhancing agents (glycerol and PEG 400) had larger influence than larger ones (PEG 3350 and 6000). The results highlighted the role of UWL as an additive barrier to permeation and indicated that diffusion through UWL is the rate-limiting step to CAF's permeation, whilst HC permeability is a partition-driven process

Le acque sotterranee del Gargano: risorse idriche integrative e di emergenza

II presente lavoro intende caratterizzare ii rapporto tra alimentazione della falda idrica sotterranea del Gargano e ii prelievo dai pozzi, gli efflussi dalle sorgenti e l’esistenza di risorse idriche sotterranee ulteriormente utilizzabili. L’area, di circa 2.000 km2, è stata discretizzata in un reticolo a maglie quadrate di 4 km2, per ciascuna delle quali è stata stimata la litologia affiorante prevalente, la quota e la pendenza media. Caratterizzato nel dettaglio ii regime termopluviometrico vigente nel Gargano, si è proceduto, per ogni celia, al calcolo delle grandezze termopluviometriche e alla definizione del bilancio idrologico. Sono state raccolte tutte le informazioni disponibili relative alle portate sorgive e ai pozzi al fine di una stima, ad oggi possibile soltanto in difetto, degli efflussi sorgivi e degli emungimenti. Al fine di meglio quantificare le portate sorgive, è stato definito un bilancio idrologico semplificato del lago di Varano. Ii metodo utilizzato è stato positivamente validato su un piccolo acquifero campione del Gargano, l’acquifero carbonatico e superficiale di Vico-Ischitella. In termini medi, dei circa 37 m3/s di precipitazioni meteoriche si stima che non meno di 8,12 m3/s finiscano per alimentare l’unità idrogeologica del Gargano. Si è stimato che non meno di 3,4 m3/s alimentino sorgenti, pan al 42 % dell’infiltrazione, mentre almeno 0,53 m3/s, pan al 7%, viene prelevato dai pozzi. Ii 50 % dell’alimentazione del Gargano dà vita ad una risorsa idrica sotterranea ii cui recapito finale non è ad oggi noto. Trattasi di non meno di 4 m3/s che si versa- no a mare senza che si abbiano notizie certe sull’ubicazione e la reale portata, anche approssimata, di tali sorgenti. La notevole entità delle portate in gioco e la buona qualità delle acque sotterranee del Gargano impongono di considerare tale acquifero profondo come una fonte per l’utilizzazione razionale e sostenibile di risorse idriche integrative e di emergenza

Gluten-free diet and gut microbiome

As the only effective therapy against diagnosed celiac disease (CD), the gluten-free diet (GFD) has inevitable repercussion on the gut microbiome composition and functionality. Being the cause or the consequence of the disease, an altered homeostasis of the gut microbiome usually affects CD patients at diagnosis. After describing the main features of this altered physiological condition, this review defines the main nutritional aspects of the GFD and elucidates how this diet regimen does not fully restore the optimal gut microbiome composition and functionality. Unbalanced ratios between beneficial and potentially harmful bacteria are frequently present in fecal materials, biopsy specimens and saliva, used as ecological model systems to observe CD. Metabolome analyses also show how an altered microbiome synthesize different metabolite with respect to healthy conditions. The review concludes illustrating the current supplementations (biotics family), which fortify the GFD with the aim of restoring the homeostasis of the gut microbiome

A simplified method to interpret the mechanism of drug release from thin polymeric films by drug diffusivity measurements

Drug-polymer interactions and their respective affinities provide vital information for developing any polymer-containing drug delivery system, such as oral films. This paper offers a simplified method to estimate the effects of interactions between the drug and polymers in corresponding film formulations using a recently developed Fickian diffusion-based methodology. Poly(vinyl alcohol-co-vinyl acetate) (PVA/PVAc) copolymers were used as film matrix formers. To systematically vary the hydrophilicity of the polymer and drug, PVA/PVAc copolymers (monomer ratios 35:65, 50:50, 74:26, 88:12, 98:2) and model drugs, hydrochlorothiazide and caffeine (with a factor 1:30 in solubility) were used. Drug diffusivities determined in a polymer solution (5 % w/v) were compared to classical in vitro drug release from the films. The drug release rate from films containing copolymers with a lower VA/VAc ratio (35:65, 50:50, and 74:26) was significantly different for the two drugs in the first 30 min. It was found that this diffusivity method provided valuable guidance in assessing drug-polymer affinity, described as the average theoretical partition constant Km/w between the polymer solution and pure aqueous media. This partition constant could be correlated to the drug release rate and serve as a simple, easy, and inexpensive screening method to provide deeper mechanistic insight into drug release mechanisms. This would allow enhanced sustainability and accelerate the formulation development process by reducing resources needed for the development of film formulations

In vitro faecal fermentation of Tritordeum breads and its effect on the human gut health

Spontaneous fermentation of Tritordeum flour enhances the nutritional potential of this hybrid cereal. However, the effect of consumption of Tritordeum sourdough bread (SDB) on gut health remains to be elucidated. This study investigated the effect of in vitro digestion and faecal fermentation of SDB compared to that of traditional baker's yeast (BYB) Tritordeum bread. After 24-h anaerobic faecal fermentation, both SDB and BYB (1% w/v) induced an increase in the relative abundances of Bifidobacterium, Megasphaera, Mitsuokella, and Phascolarctobacterium genera compared to baseline, while concentrations of acetate and butyrate were significantly higher at 24 h for SDB compared to those for BYB. Integrity of intestinal epithelium, as assessed through in vitro trans-epithelial electrical resistance (TEER) assay, was slightly increased after incubation with SDB fermentation supernatants, but not after incubation with BYB fermentation supernatants. The SDB stimulated in vitro mucosal immune response by inducing early secretion of inflammatory cytokines, IL-6 and TNF-α, followed by downregulation of the inflammatory trigger through induction of anti-inflammatory IL-10 expression. Overall, our findings suggest that Tritordeum sourdough can modulate gut microbiota fermentation activity and positively impact the gut health

Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin

The objective of this work was to optimize a thermosensitive in situ gelling formulation to improve intranasal and nose-to-brain delivery of the antiepileptic drug carbamazepine (CBZ). A preliminary procedure of vehicles obtained just mixing different fractions of poloxamer 407 (P407) and poloxamer 188 (P188) revealed preparations with phase transition temperatures, times to gelation and pH values suitable for nasal delivery. Subsequently, the mucoadhesive properties of the most promising formulations were tuned by adding hydroxypropylmethylcellulose types of different viscosity grades, and the effect of the adhesive polymers was evaluated by testing in vitro time and strength of mucoadhesion on specimens of sheep nasal mucosa. The formulation that showed the greatest mucoadhesive potential in vitro, with a time and force of mucoadhesion equal to 1746,75 s and 3.66 × 10-4 N, respectively, was that composed of 22% P407, 5% P188 and 0.8% HPMC low-viscous and it was further investigated for its ability to increase drug solubility and to control the release of the drug. Lastly, the capability of the candidate vehicle to ensure drug permeation across the biomimetic membrane Permeapad®, an artificial phospholipid-based barrier with a stratified architecture, and the same barrier enriched with a mucin layer was verified. The final formulation was characterized by a pH value of 6.0, underwent gelation at 32.33◦C in 37.85 s, thus showing all the features required by in situ gelling thermosensitive preparations designed for nasal delivery and, more notably, it conserved the ability to favor drug permeation in the presence of mucin. These findings suggest that the optimized gelling system could be a promising and easy to realize strategy to improve CBZ delivery to the brain exploiting both a direct and indirect pathway