Encapsulation of Olive Leaf Polyphenol-Rich Extract in Polymeric Micelles to Improve Its Intestinal Permeability.

In the present study, polymeric micelles were developed to improve the intestinal permeability of an extract of Olea europaea L. leaf with a high content of total polyphenols (49% w/w), with 41% w/w corresponding to the oleuropein amount. A pre-formulation study was conducted to obtain a stable formulation with a high loading capacity for extract. The freeze-drying process was considered to improve the stability of the formulation during storage. Micelles were characterized in terms of physical and chemical properties, encapsulation efficiency, stability, and in vitro release. The optimized system consisted of 15 mg/mL of extract, 20 mg/mL of Pluronic L121, 20 mg/mL of Pluronic F68, and 10 mg/mL of D-α-tocopheryl polyethylene glycol succinate (TPGS), with dimensions of 14.21 ± 0.14 nm, a polydisersity index (PdI) of 0.19 ± 0.05 and an encapsulation efficiency of 66.21 ± 1.11%. The influence of the micelles on polyphenol permeability was evaluated using both Parallel Artificial Membrane Permeability Assay (PAMPA) and the Caco-2 cell monolayer. In both assays, the polymeric micelles improved the permeation of polyphenols, as demonstrated by the increase in Pe and Papp values.

Rheological and low field NMR characterization of hydrophobically-modified PEG hydrogels for drug delivery.

The focus of this work is on the characterization of hydrophobically-modified polyethylene glycol hydrogels, to be used as drug delivery systems, by means of the combined used of rheology and low field Nuclear Magnetic Resonance. Indeed, these two techniques allowed understanding how the transient physical bonds deriving from hydrophobic association superimpose to the pre-existing covalent bonds. We found that the improvement of physical bonds can be achieved not only by increasing the content of hydrophobic segments but also by using thermal treatments after hydrogel preparation. Moreover, we proved the reliability of an overall interpretative model linking the dependence of the shear modulus and the average magnetic relaxation time. Finally, we proposed a new mathematical approach for the determination of the magnetic relaxation spectrum. This approach reduced the computational heaviness of the procedure and allowed to easily discern the different contributes nested in the overall magnetic relaxation spectrum, an aspect that the traditional approach cannot provide directly.

Expandable Drug Delivery Systems Based on Shape Memory Polymers: Impact of Film Coating on Mechanical Properties and Release and Recovery Performance.

Retentive drug delivery systems (DDSs) are intended for prolonged residence and release inside hollow muscular organs, to achieve either local or systemic therapeutic goals. Recently, formulations based on shape memory polymers (SMPs) have gained attention in view of their special ability to recover a shape with greater spatial encumbrance at the target organ (e.g., urinary bladder or stomach), triggered by contact with biological fluids at body temperature. In this work, poly(vinyl alcohol) (PVA), a pharmaceutical-grade SMP previously shown to be an interesting 4D printing candidate, was employed to fabricate expandable organ-retentive prototypes by hot melt extrusion. With the aim of improving the mechanical resistance of the expandable DDS and slowing down relevant drug release, the application of insoluble permeable coatings based on either Eudragit® RS/RL or Eudragit® NE was evaluated using simple I-shaped specimens. The impact of the composition and thickness of the coating on the shape memory, swelling, and release behavior as well as on the mechanical properties of these specimens was thoroughly investigated and the effectiveness of the proposed strategy was demonstrated by the results obtained.

Hydrophobically-Modified PEG Hydrogels with Controllable Hydrophilic/Hydrophobic Balance.

This work reports on a novel method to synthesize hydrophobically-modified hydrogels by curing epoxy monomers with amines. The resulting networks contain hydrophilic poly(ethylene glycol) (PEG) segments, poly(propylene glycol) (PPG) segments, and C18 alkyl segments. By varying the content of C18 segments, networks with different hydrophilic-lipophilic balance (HLB) are obtained. All networks show an amphiphilic behavior, swelling considerably both in organic solvents and in aqueous media. In the latter they display a thermosensitive behavior, which is highly affected by the network HLB and the pH of the solution. A decrease in HLB results in an increment of the polymer weight content (wp) due to hydrophobic association. Furthermore, a reduction in HLB induces a remarkable increase in initial modulus, elongation at break and tensile strength, especially when wp becomes greater than about 10%. Low field nuclear magnetic resonance (LF-NMR) experiments evidence that, when HLB decreases, a sudden and considerable increase in hydrogel heterogeneity takes place due to occurrence of extensive physical crosslinking. Available data suggest that in systems with wp ≳ 10% a continuous physical network superimposes to the pre-existing chemical network and leads to a sort of double network capable of considerably improving hydrogel toughness.

Size-Induced Constraint Effects on Crack Initiation and Propagation Parameters in Ductile Polymers.

Fracture mechanics are of high interest for the engineering design and structural integrity assessment of polymeric materials; however, regarding highly ductile polymers, many open questions still remain in terms of fully understanding deformation and fracture behaviors. For example, the influence of the constraint and specimen size on the fracture behavior of polymeric materials is still not clear. In this study, a polymeric material with an elastic plastic deformation behavior (ABS, acrylonitrile butadiene styrene) is investigated with regard to the influence of constraint and specimen size. Different single-edge notched bending (SENB) specimen sizes with constant geometrical ratios were tested. The material key curve was used to investigate differences in the constraint, where changes for small and large specimen sizes were found. Based on a size-independent crack resistance curve (J-R curve), two apparent initiation parameters (J0.2 and Jbl) were determined, namely, the initiation parameter Jini (based on the crack propagation kinetics curve) and the initiation parameter JI,lim (based on an ESIS TC 4 draft protocol). It was found that J0.2 and Jbl could be used as crack initiation parameters whereby Jini and JI,lim are indicative of the onset of stable crack growth.

Expandable drug delivery system for gastric retention based on shape memory polymers: Development via 4D printing and extrusion.

Several diseases would benefit from prolonged drug release provided by systems retained in the stomach for extended time periods. Expandable gastroretentive devices are administered in a collapsed configuration enabling swallowing and regain in situ their native shape having larger spatial encumbrance, thus hindering voidance through the wide open pylorus. An expandable system for gastric retention was here proposed relying on the shape memory behavior of pharmaceutical-grade poly(vinyl alcohol). Different original configurations to be recovered upon exposure to aqueous fluids at 37 °C, potentially enabling gastric retention, were conceived. Prototypes containing allopurinol were directly manufactured by fused deposition modeling or shaped by purposely-designed templates from hot melt extruded rods immediately after production. Various temporary shapes, in principle suitable for administration, were programmed by manual deformation of samples by means of specific templates, under defined temperature conditions. In 0.1 N hydrochloric solution at 37 °C, the prototypes recovered their original shape, reaching the desired spatial encumbrance within few minutes. Release from the samples, although of relatively short duration, was independent of the original shape and processing undergone, and was noticeably slowed down by application of Eudragit® RS/RL-based coatings.

Influence of the pH control strategy and reactor volume on batch fermentative hydrogen production from the organic fraction of municipal solid waste.

Three different experimental sets of runs involving batch fermentation assays were performed to evaluate the influence of the experimental conditions on biological hydrogen production from the source-separated organic fraction of municipal solid waste collected through a door-to-door system. The fermentation process was operated with and without automatic pH control, at a pH of 5.5 and 6.5, food-to-microorganism ratios of 1/3 and 1/1 (wet weight basis) and with different working volumes (0.5 and 3 L). The experimental results showed that the pH control strategy and the reactor volume did not affect the final hydrogen production yield but played an important role in determining the time evolution of the process. Indeed, although the different experimental conditions tested yielded comparable hydrogen productions (with maximum average values ranging from 68.5 to 88.5 NLH2 (kgTVSOF)-1), the automatic pH control strategy improved the process from the kinetic viewpoint resulting in a t95 reduction from an average of 34.9 h without automatic pH control to an average of 19.5 h.

Rheological Characterization of Ethylcellulose-Based Melts for Pharmaceutical Applications.

Rheological characterization of ethylcellulose (EC)-based melts intended for the production, via micro-injection moulding (µIM), of oral capsular devices for prolonged release was carried out. Neat EC, plasticized EC and plasticized EC containing solid particles of a release modifier (filler volume content in the melt around 30%) were examined by capillary and rotational rheometry tests. Two release modifiers, differing in both chemical nature and particle geometry, were investigated. When studied by capillary rheometry, neat EC appeared at process temperatures as a highly viscous melt with a shear-thinning characteristic that progressively diminished as the apparent shear rate increased. Thus, EC as such could not successfully be processed via µIM. Plasticization, which induces changes in the material microstructure, enhanced the shear-thinning characteristic of the melt and reduced considerably its elastic properties. Marked wall slip effects were noticed in the capillary flow of the plasticized EC-based melts, with or without release modifier particles. The presence of these particles brought about an increase in viscosity, clearly highlighted by the dynamic experiments at the rotational rheometer. However, it did not impair the material processability. The thermal and rheological study undertaken would turn out a valid guideline for the development of polymeric materials based on pharma-grade polymers with potential for new pharmaceutical applications of µIM.

Leaching behaviour of hazardous waste under the impact of different ambient conditions.

The overall objective of this study is to provide an improved basis for the assessment of the leaching behaviour of waste marked as hazardous partly stabilised (European waste catalogue code 19 03 04∗). Four samples of hazardous partly stabilised waste were subjected to two leaching tests: up-flow column tests and batch equilibrium tests. The research was carried out in two directions: the first aims at comparing the results of the two experimental setups while the second aims at assessing the impact of different ambient conditions on the leaching behaviour of waste. Concerning this latter objective the effect of mesophilic temperature, mechanical constraints and acid environment were tested through column percolation tests. Results showed no significant differences between batch and column leaching test outcomes when comparing average concentrations calculated at a liquid to solid ratio of 10:1 l kg-1 TS. Among the tested ambient conditions, the presence of an acid environment (pH=4.5) accelerated the leaching process resulting in a higher cumulative released quantity measured on the majority of the investigated polluting substances. On the contrary, the effect of temperature and mechanical constraints seemed to not affect the process showing final contents even lower than values found for the standard test. This result was furthermore confirmed by the application of the principal component analysis.

Biochemical methane potential tests of different autoclaved and microwaved lignocellulosic organic fractions of municipal solid waste.

The aim of this research was to enhance the anaerobic biodegradability and methane production of two synthetic Organic Fractions of Municipal Solid Waste with different lignocellulosic contents by assessing microwave and autoclave pre-treatments. Biochemical Methane Potential assays were performed for 21days. Changes in the soluble fractions of the organic matter (measured by soluble chemical oxygen demand, carbohydrates and proteins), the first order hydrolysis constant kh and the cumulated methane production at 21days were used to evaluate the efficiency of microwaving and autoclaving pretreatments on substrates solubilization and anaerobic digestion. Microwave treatment led to a methane production increase of 8.5% for both the tested organic fractions while autoclave treatment had an increase ranging from 1.0% to 4.4%. Results showed an increase of the soluble fraction after pre-treatments for both the synthetic organic fractions. Soluble chemical oxygen demand observed significant increases for pretreated substrates (up to 219.8%). In this regard, the mediocre results of methane's production led to the conclusion that autoclaving and microwaving resulted in the hydrolysis of a significant fraction of non-biodegradable organic substances recalcitrant to anaerobic digestion.

Cow's milk protein allergy in children: a practical guide.

A joint study group on cow's milk allergy was convened by the Emilia-Romagna Working Group for Paediatric Allergy and by the Emilia-Romagna Working Group for Paediatric Gastroenterology to focus best practice for diagnosis, management and follow-up of cow's milk allergy in children and to offer a common approach for allergologists, gastroenterologists, general paediatricians and primary care physicians.The report prepared by the study group was discussed by members of Working Groups who met three times in Italy. This guide is the result of a consensus reached in the following areas. Cow's milk allergy should be suspected in children who have immediate symptoms such as acute urticaria/angioedema, wheezing, rhinitis, dry cough, vomiting, laryngeal edema, acute asthma with severe respiratory distress, anaphylaxis. Late reactions due to cow's milk allergy are atopic dermatitis, chronic diarrhoea, blood in the stools, iron deficiency anaemia, gastroesophageal reflux disease, constipation, chronic vomiting, colic, poor growth (food refusal), enterocolitis syndrome, protein-losing enteropathy with hypoalbuminemia, eosinophilic oesophagogastroenteropathy. An overview of acceptable means for diagnosis is included. According to symptoms and infant diet, three different algorithms for diagnosis and follow-up have been suggested.

Characterization of irritable bowel syndrome and constipation in children with allergic diseases.

Allergy is believed to play a role in the pathogenesis of irritable bowel syndrome (IBS) and constipation. We investigated whether allergic patients are more prone to constipation or IBS. In a multicenter study, two groups of outpatient children aged 3-13 years were included. In group 1, children with allergic symptoms were enrolled. Group 2 consisted of nonallergic children. In both groups, the assessment of IBS and constipation was carried out using a questionnaire based on the Rome criteria for functional gastrointestinal disorders. All children were examined and underwent skin prick tests (SPT) to foods and aeroallergens. The allergic group (n=196) and controls (n=127) were comparable with respect to sex, age, and anthropometric parameters. IBS was found in 6.6% of the allergic children and in 6.3% of the controls (p=0.581). The frequency of constipation was similar in the two groups. In allergic children, positive SPTs to food and self-reported reactions to food were associated with IBS. Our results show that evaluation of constipation comorbidity is not required in allergic children. In allergic children with positive SPT to foods attention may be paid to IBS symptoms.