Rotor-Stator Emulsification in the Turbulent Inertial Regime: Experiments toward a Robust Correlation for the Droplet Size.

The Sauter mean diameter, d32, is a representative parameter in emulsions that indicates the average size of the oil droplets once the emulsion becomes stable. Several mathematical and physical approaches have been employed in the literature to seek expressions for d32 under different conditions. The present work sheds light on this rich literature and emphasizes that the characterization of emulsions is still a fertile field for investigation. In this paper, a new Π-theorem-based model to predict the normalized Sauter mean diameter for the specific case of rotor-stator emulsification is sought by applying a multiple regression analysis on experimental data of oil-in-water (O-W) emulsions produced using three different oils: paraffin, soybean oil, and isopropyl myristate, at different oil-to-water (O/W) ratios and rotor speeds. The proposed model quantifies the roles of the viscous, inertial, and interfacial tension forces, besides the O/W ratio, in the emulsification process within the turbulent inertial subrange. The developed empirical correlation is then contrasted with relevant literature models for reliability assessment; predictions of the present explicit model are proven to be more accurate for the fluid properties and the experimental conditions under study.

Potential Use of PLA-Based Films Loaded with Antioxidant Agents from Spent Coffee Grounds for Preservation of Refrigerated Foods.

The aim of this work concerned the production of an active food packaging suitable for refrigerated foods. Polylactic-acid-based films were produced by optimizing the solvent casting technique and testing different loadings of extracts obtained from spent coffee grounds. Indeed, an extract obtained by high-pressure and -temperature extraction (HPTE) and a further purified extract by liquid-liquid extraction (LLE) were separately used as active agents, and the effects on packaging features and active compounds migration were analyzed. The selected active agents showed antioxidant and lipid peroxidation inhibition effects on food simulants (peroxide values of 9.2 ÷ 12.0 meqO2/kg extra virgin olive oil), demonstrating the possibility of enhancing food shelf life. In addition, significant effects on the packaging structure due to the presence of the extract were observed, since it can enhance gas barrier properties of the polymer (O2 permeability of 1.6 ÷ 1.3 × 10-9 cm2/s) and confer better processability. In general, the HPTE extract exhibited better performances than the further purified extract, which was due to the presence of a complex pool of antioxidants and the browning effect on the film but a limited loading capacity on the polymer (840 µg caffeine/g PLA), while higher loading capabilities were enabled using LLE extract.

Improvement of Natural Polymeric Films Properties by Blend Formulation for Sustainable Active Food Packaging.

Active packaging manufactured with biopolymers extracted from agri-food waste is one of the most innovative and eco-sustainable strategies for maintaining food quality. However, biopolymers often present poor performances, which hinders their competitiveness compared with plastics. This work focused on developing and optimizing a natural polymeric blend produced by solvent casting based on zein and chitosan to improve the pure biopolymers' properties. The best results were obtained by blending zein and chitosan in a 1:2 weight ratio. The films were characterized in terms of morphology, mechanical and oxygen barrier properties, thermal stability, transparency and wettability. The blend production allowed us to obtain lower brittleness and lower stiffness materials compared with pure polymer films, with oxygen permeability values two orders of magnitude lower than pure zein, better optical properties with respect to pure chitosan and good thermal stability. The wettability properties of the blend did not result in being altered with respect to the single polymer, which was found to have hydrophilic behavior, highlighting the strong influence of glycerol used as a plasticizer. The results suggested that the polymer blending strategy is a viable and cost-effective method for producing packaging materials as alternatives to plastics.

Bevacizumab encapsulation into PLGA nanoparticles functionalized with immunouteroglobin-1 as an innovative delivery system for atherosclerosis.

Atherosclerosis represents one of the main causes of death in the Western world. It is a multifactorial pathology characterized by lesions that reduce the lumen of the vessels causing serious clinical events. The extra-domain B of fibronectin is overexpressed during angiogenesis and in tissues undergoing growth and extensive remodeling, i.e., atherosclerotic plaque. Bevacizumab is a recombinant humanized monoclonal antibody that can play a central role against angiogenesis reducing the risk associated with this process in atherosclerosis. In this work, an innovative nanosystem for the targeted delivery of bevacizumab to the atherosclerotic lesion is proposed. A production protocol for poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles loaded with bevacizumab and functionalized with immunouteroglobin-1 was designed. Once functionalized nanoparticles with immunouteroglobin-1 were produced, they were characterized in terms of morphology, mean diameter, ζ-potential, association and conjugation efficiencies, bevacizumab release profile, both in phosphate buffered saline and in serum, bevacizumab stability after release, cytocompatibility, and hemocompatibility. Nanoparticle mean diameter was in the range of 217-265 nm, their surface charge was between -22 and -8 mV, and the association and conjugation efficiencies of about 76 and 59 %, respectively. Fourier transform infrared spectroscopy analysis confirmed the functionalization of their surface with immunouteroglobin-1. In vitro assays showed that the studied nanoparticles were cytocompatible, once in contact with human endothelial and murine macrophage cell lines up to 72 h, and hemocompatible, once in contact with red blood cells, at different concentrations of encapsulated bevacizumab (0.1, 1, 10, and 100 µg/mL).

Bevacizumab-Controlled Delivery from Polymeric Microparticle Systems as Interesting Tools for Pathologic Angiogenesis Diseases.

This work is a comparative study among three different biocompatible and biodegradable polymers, poly(lactic-co-glycolic acid), poly(ε-caprolactone), and poly(lactic acid), used to produce microparticles for the encapsulation of bevacizumab for drug delivery purposes. All the formulations were produced using the double emulsion water-oil-water evaporation method and characterized in terms of particle mean diameter, particle size distribution, and bevacizumab entrapment efficiency. Bevacizumab cumulative release was taken into consideration to study the dissolution kinetics from the three different polymeric delivery platforms for a period of 50 days at 37 °C in phosphate buffered saline and mathematical models of the drug release kinetic were attempted in order to describe the release phenomena from the different types of the studied microparticles. Finally, cell viability on human endothelial cell line EA.hy926 was studied to define the maximum cytocompatible concentration for each microsystem, registering the mitochondrial functionality through MTS assay.

Innovative nanotools for vascular drug delivery: the atherosclerosis case study.

Cardiovascular diseases are the leading cause of mortality in the Western world. Among them, atherosclerosis represents one of the most common diseases in the modern society due to a common sedentary lifestyle, high-fat diet, and smoking. In the near future, a new approach could potentially improve the therapy of vascular pathologies, where to date the non-specific treatments present several limitations, such as poor biodistribution, quick elimination from the body, and undesired side-effects. In this field, nanotechnology has a great potential for the therapy and diagnosis of atherosclerosis with more and more recent and innovative publications. This review is a critical analysis of the results reported in the literature regarding the different and possible new approaches for the therapy and diagnosis of atherosclerosis.

Innovations in Smart Packaging Concepts for Food: An Extensive Review.

Innovation in food packaging is mainly represented by the development of active and intelligent packing technologies, which offer to deliver safer and high-quality food products. Active packaging refers to the incorporation of active component into the package with the aim of maintaining or extending the product quality and shelf-life. The intelligent systems are able to monitor the condition of packaged food in order to provide information about the quality of the product during transportation and storage. These packaging technologies can also work synergistically to yield a multipurpose food packaging system. This review is a critical and up-dated analysis of the results reported in the literature about this fascinating and growing field of research. Several aspects are considered and organized going from the definitions and the regulations, to the specific functions and the technological aspects regarding the manufacturing technologies, in order to have a complete overlook on the overall topic.

Poly (Lactic-co-Glycolic Acid) Nanoparticles and Nanoliposomes for Protein Delivery in Targeted Therapy: A Comparative In Vitro Study.

Over the previous years, the design, development, and potential application of nanocarriers in the medical field have been intensively studied for their ability to preserve drug properties, especially their pharmacological activity, and to improve their bioavailability. This work is a comparative study between two different types of nanocarriers, poly (lactic-co-glycolic acid)-based nanoparticles and phosphatidylcholine-based nanoliposomes, both prepared for the encapsulation of bovine serum albumin as a model protein. Polymeric nanoparticles were produced using the double emulsion water-oil-water evaporation method, whereas nanoliposomes were obtained by the thin-film hydration method. Both nanocarriers were characterized by morphological analysis, particle mean size, particle size distribution, and protein entrapment efficiency. Invitro release studies were performed for 12 days at 37 °C. In order to explore a possible application of these nanocarriers for a targeted therapy in the cardiovascular field, hemolytic activity and biocompatibility, in terms of cell viability, were performed by using human red blood cells and EA.hy926 human endothelial cell line, respectively.

* An Engineered Multiphase Three-Dimensional Microenvironment to Ensure the Controlled Delivery of Cyclic Strain and Human Growth Differentiation Factor 5 for the Tenogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells.

At present, injuries or rupture of tendons are treated by surgical repair or conservative approaches with unpredictable clinical outcome. Alternative strategies to repair tendon defects without the undesirable side effects associated with the current options are needed. With this in mind, a tissue engineering approach has gained considerable attention as a promising strategy. Here we investigated a synthetic three-dimensional (3D) microenvironment able to interact with stem cells and inducing, via coupled biochemical and physical signals, their early commitment toward the tenogenic lineage. This multiphase 3D construct consisted of a braided hyaluronate elastic band merged with human bone marrow mesenchymal stem cells (hBMSCs) and poly-lactic-co-glycolic acid microcarriers loaded with human growth differentiation factor 5 (hGDF-5) by means of fibrin hydrogel. The multiphase structure allowed hBMSC culture under cyclic strain within a microenvironment where a controlled amount of hGDF-5 was regularly delivered. The cooperative biochemical and physical stimuli induced significantly increased expression of tenogenic markers, such as collagen type I and III, decorin, scleraxis, and tenascin-C, within only 3 days of dynamic hBMSC culture. This approach opens exciting perspectives for future development of engineered tendon tissue substitutes.

Injectable PLGA/Hydroxyapatite/Chitosan Microcapsules Produced by Supercritical Emulsion Extraction Technology: An In Vitro Study on Teriparatide/Gentamicin Controlled Release.

Supercritical emulsion extraction (SEE) is proposed as a green and effective strategy for the fabrication of chitosan-covered poly-lactic-co-glycolic acid (chi-PLGA) injectable microcapsules for the controlled release of teriparatide (THA) and teriparatide/gentamicin sulfate (THA/Gen). These formulations can be used for locally bone pathologies treatment or in complex fracture healing of aged patients. Several oil-water (o-w) and water-oil-water (w-o-w) emulsions were processed by SEE to produce multifunctional microcapsules containing hydroxyapatite (HA) within a poly-lactic-co-glycolic acid (PLGA) matrix (up to 24 mg/g) and with both THA (0.45 mg/g) and Gen (up to 9 mg/g). Chitosan coating was also successfully added, as external layer (0.4 µm). SEE-fabricated microcapsules showed good encapsulation efficiency (up to 90%) for all the drugs tested and a mean size ranging between 1.4 (±0.4) µm and 2.2 (±0.5) µm. Different drug amounts loaded and microcapsules compositions assured a controlled drug release over a wide range of times and concentrations, as in vitro monitored in PBS medium at 37°C for 15/20 days. HA embedded into the biopolymer structure delayed the THA release profile; chitosan coating strongly reduced the initial drug "burst" release. In addition, the coencapsulation of both THA and Gen, which have very different water solubility, accelerated the release profile of the less water-soluble drug. No drugs degradation was also monitored after the SEE manufacturing. Apparent drug diffusivities (D) were calculated by fitting of the release profiles. In the case of Gen, D ranged between 2.9 × 10(-8) and 1.6 × 10(-9) cm(2)s(-1) if the drug was entrapped in simple PLGA or in the chitosan-coated microcapsules, respectively. In the case of THA, the calculated values ranged between 8.1 × 10(-9) and 7.4 × 10(-10) cm(2)s(-1) when the drug was entrapped in PLGA/HA microcapsules or in the chitosan-coated ones, respectively. These mass transfer values are consistent with the different release behaviors observed and confirmed the possibility of multicomponent microcapsules fabrication by SEE.

Liposomes Size Engineering by Combination of Ethanol Injection and Supercritical Processing.

Supercritical fluid extraction using a high-pressure packed tower is proposed not only to remove the ethanol residue from liposome suspensions but also to affect their size and distribution leading the production of nanosomes. Different operating pressures, temperatures, and gas to liquid ratios were explored and ethanol was successfully extracted up to a value of 400 ppm; liposome size and distribution were also reduced by the supercritical processing preserving their integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy observations. Operating at 120 bar and 38°C, nanosomes with a mean diameter of about 180 ± 40 nm and good storage stability were obtained. The supercritical processing did not interfere on drug encapsulation, and no loss of entrapped drug was observed when the water-soluble fluorescein was loaded as a model compound. Fluorescein encapsulation efficiency was 30% if pure water was used during the supercritical extraction as processing fluid; whereas an encapsulation efficiency of 90% was obtained if the liposome suspension was processed in water/fluorescein solution. The described technology is easy to scale up to an industrial production and merge in one step the solvent extraction, liposome size engineering, and an excellent drug encapsulation in a single operation unit.

Au-PLA nanocomposites for photothermally controlled drug delivery.

Stimuli-responsive drug delivery systems were obtained by encapsulating near-infrared (NIR) sensitive hollow gold nanoshells (HGNs) together with the molecule to be released into biodegradable poly-lactic acid (PLA) sub-micron particles. The rapid heating of the PLA particles caused by NIR radiation enabled use of the PLA-HGN composites as a photo-triggered drug release system. Rhodamine was used as a test molecule to obtain release profiles under different irradiation conditions. HGNs (32 nm diameter, 4.5 nm shell thickness) were synthesized via galvanic replacement of cobalt nanoparticles, using poly(vinylpyrrolidone) (PVP) as a stabilizer. PLA-HGN sub-micron particles (with mean diameters around 200 nm) encapsulating rhodamine were obtained using the supercritical emulsion extraction (SEE) technique. A good gold dispersion and a loading efficiency around 50% in the polymeric matrix were obtained for different HGN loadings. The release rate could be tuned by controlling the intensity of NIR exposition. Rhodamine release was completed in less than 10 hours when applying intense NIR irradiation for a few minutes, whereas 12 days of release was necessary in its absence. The system also allowed rhodamine release in a pulsed pattern.

PLGA microdevices for retinoids sustained release produced by supercritical emulsion extraction: continuous versus batch operation layouts.

Retinyl acetate (RA) was selected as a model compound to be entrapped in poly(lactic-co-glycolic)acid (PLGA) microspheres using supercritical emulsion extraction (SEE). Several oil-in-water emulsions prepared using acetone and aqueous glycerol (80% glycerol, 20% water) were processed using supercritical carbon dioxide (SC-CO2 ) to extract the oily phase and to induce microspheres formation. The characteristics of the microspheres obtained by conventional liquid emulsion extraction and SEE were also compared: SEE produced spherical and free flowing microspheres, whereas the conventional liquid-liquid extraction showed large intraparticles aggregation. Emulsion extraction by SC-CO2 technology was tested using two different operation layouts: batch (SEE-B) and continuous (SEE-C). SEE-C was performed using a packed tower to produce emulsion/SC-CO2 contact in countercurrent mode, allowing higher microsphere recovery and process efficiencies. Operating at 80 bar and 36°C, SEE-C produced PLGA/RA microspheres with mean sizes between 3.3 and 4.5 µm with an excellent encapsulation efficiency of 80%-90%. Almost all the drug was released in about 6 days when charged at 2.7% (w/w), whereas only 40% and 10% of RA were released in the same period of time when the charge was 5.2% and 8.8% (w/w), respectively. Release kinetics constants calculated from the experimental data, using a mathematical model, were also proposed and discussed.