The stability of diclofenac sodium (DS) in liquid formulation is influenced by environmental factors such as temperature, humidity and light. The encapsulation of this drug in solid lipid nanoparticles (SLNs) can offer a useful strategy to protect it from degradation. The present study shows the potential of membrane nanoprecipitation (MN) as a productive and advantageous method for the formulation of cocoa butter-based SLNs to improve the photostability of DS. Conventional batch nanoprecipitation and MN were explored by varying the formulation parameters and process conditions to obtain SLNs. The MN produced SLNs with an average size of 421 ± 14 nm, a high encapsulation efficiency of 95 ± 3.2

Plant growth-promoting microorganisms represent a sustainable alternative to chemical inputs for improving crop yield and nutritional quality. Their commercialization is limited by the lack of effective formulation technologies and fermentations. In fact, their functionality is related to the implementation of a protective matrix required to enhance microbial survival and application efficiency. To hasten their adoption, the development of advanced formulation technologies that can be easily scaled up, operate under mild conditions, and ensure cell immobilization efficiency and survival is needed. The potential of microbial-based biostimulants can be further promoted by the implementation of sustainable and efficient fermentation processes capable of yielding high concentrations of viable microbial cells. In the present study, membrane emulsification was applied as an advanced encapsulation approach to produce alginate capsules containing Kosakonia pseudosacchari TL13, a promising biofertilizer bacterial strain. Citrus waste biomass was converted into K. pseudosacchari TL13 biomass in a bioreactor fermentation, and the microorganism and the fermentation-derived bioactive compounds were simultaneously encapsulated. Results demonstrated that (i) membrane technology can be used to redesign the conventional encapsulation process based on emulsification with reduced shear stress and high efficiency in terms of formulation quality and microorganism loading and survival, (ii) high concentrations of biomass and added-value products (i.e., exopolysaccharides) can be obtained by using low-cost and easily available food waste, and (iii) the downstream of the process can be simplified by using the whole broth as material for biostimulant production. Overall, the proposed integrated strategy permits providing a sustainable process for microbial-based biostimulant production based on process efficiency and environmental impact.

Materials combining organic and inorganic components at the nano-and submicron scale exhibit unique properties owing to their nanoscale architecture and the synergistic interplay of the constituent phases. Their main drawbacks include challenges in achieving nanoscale homogeneity, which can affect functionality, and the requirement for developing new and advanced manufacturing methods. Nanoprecipitation has emerged as valuable technique for hybrid particles production widely recognized for its simplicity and energy efficiency although its scalability and reproducibility remain a significant challenge. The present work explores the use of membrane nanoprecipitation (MN) for the continuous production of polymer-coated inorganic particles with finely tuned sizes and uniform size distributions. The coating efficacy of polyvinyl alcohol (PVA) on cubic zeolites (similar to 100 nm) to obtain submicrometric composite particles was systematically investigated by modulating key parameters, including polymer and surfactant concentrations, solvent-to-non-solvent volumetric ratios, and polymer-to-inorganic mass ratios. The study attempts to establish clear guidelines for the application of the membrane-based coating process into the development of hybrid particles. Results highlight the advantages of the membrane system in achieving uniform, aggregate-free suspensions and its ability to tune the production of composite submicron particles.

Metal nanostructures with Surface Plasmon Resonance (SPR) properties have garnered interest in applications like optical sensing, photothermal therapy, and optical waveguiding. While synthetic polymers commonly serve as carriers, integrating metal nanostructures with natural-based polymers enhances biocompatibility and biodegradability. With its amine and hydroxyl groups, zein is an ideal material for metal ion interaction enabling efficient surface functionalization of zein nanoparticles (ZNPs). Here, it is demonstrated that zein not only could act as an ideal biopolymeric carrier but also provide an optimal platform for synthesizing anisotropic structures such as palladium nanosheets (PdNS). Two approaches were explored: (i) a two-step approach, involving the preparation of ZNPs via membrane nanoprecipitation (MN) followed by in situ PdNS synthesis using K₂PdCl₄ in a gas-phase carbon monoxide (CO)-confined growth method; and (ii) one-step approach, employing the Pd precursor as the non-solvent during ZNPs nanoprecipitation. For ZNPs-Pd synthesized by the two-step method the influence of variables such as pH, salt, surfactant, and ethanol were evaluated. For one-step approach, to address scalability limitations, ZNPs-Pd nanoprecipitation was performed in a continuous MN process using a 0.2 µm SPG membrane, without using stabilizing agents. TEM imaging confirmed successful, selective PdNS formation on ZNP surfaces without compromising structural integrity. ICP-MS analysis validated the high yield. The ZNPs-Pd demonstrated photothermal activity in the NIR region, achieving temperatures up to 49.6°C. Despite thermal stress, ZNPs-Pd maintained structural stability, marking a significant advancement in the scalable fabrication of biocompatible, photothermally active nanostructures for biomedical and optical applications.

An integrated system of three membrane bioreactors (MBRs) has been developed that cascades three different enzymatic reactions. The integrated system was applied to produce hydroxytyrosol acetate from oleuropein extracted from olive leaves. Different reactor configurations for each reaction were tested and individually optimized to select the MBR to ensure high conversion and continuous production of oleuropein aglycone (OA), hydroxytyrosol (HY) and hydroxytyrosol acetate (HA). Based on this study, the most performing configuration of the integrated system was identified. In the first reaction, oleuropein was converted to OA using a biocatalytic membrane reactor (BMR) with immobilized β-glucosidase in polymeric membranes (conversion 95 %). The OA was then fed to another BMR, where it was converted to HY (conversion: 70 %) by an immobilized mutant of the promiscuous hydrolase/acyltransferase (PestE) (from the thermophilic archaeon Pyrobaculum calidifontis VA1). The HY produced was then acetylated using PestE immobilized on magnetic nanoparticles in a multiphase MBR (conversion: 98 %) and simultaneously extracted (extraction: 98 %) in ethyl acetate. The work demonstrates that continuous cascade enzymatic reactions can be engineered using artificial membranes to tailor enzyme compartmentalization, mass transport and phase contact according to reaction requirements. Besides, environmental factors proved the sustainability of the integrated membrane bioreactive system.

The emergence of green chemistry and engineering principles to enforce sustainability aspects has ensured the prevalence of green solvents and green processes. Our study addresses this quest by exploring drug delivery applications of hydrophobic deep eutectic solvents (DESs) which are alternative green solvents. Initially, this work showcases the hydrophobic drug solubilization capabilities of a natural hydrophobic DES, menthol, and decanoic acid. To consider biomedical applications wherein polar media are encountered, this work further demonstrates the potential drug delivery application of these systems by encapsulating the anti-inflammatory local anesthetic lidocaine in hydrophobic DES-in-water nanoemulsions. NMR studies confirm the high solubility of the hydrophobic drug in hydrophobic DES comprising menthol and decanoic acid (1:2 molar ratio). Ultrasound emulsification and energy-efficient membrane emulsification techniques were employed to disperse 4% (v/v) DES into a 2% (w/w) Tween 20 surfactant aqueous solution. An isoporous microengineered membrane (nominal pore size similar to 9 mu m) was used to produce lidocaine-loaded DES-based nanoemulsions. Such membrane-assisted nanoemulsification was possible because the hydrophobic DES exhibits relatively low interfacial tension with the continuous phase and acts as a cosurfactant. Moreover, increased concentrations of lidocaine within the DES resulted in a further decrease in the interfacial tension and a lower melting point. Among the kinetic models analyzed to evaluate the release of lidocaine encapsulated in hydrophobic DES-in-water nanoemulsions, the Korsmeyer-Peppas kinetic model provided the best fit. The release constant "n" of <0.5 indicates that the drug release mechanism is predominantly governed by diffusion. Additionally, cytotoxicity against various human cell lines demonstrated the nanoemulsion's potential for anti-inflammatory drug delivery applications. Consequently, the nanoemulsion of DES presents a promising solution for the effective loading and delivery of poorly soluble drugs. This innovative approach enhances drug solubility and bioavailability, providing a versatile platform for controlled drug release. By leveraging the advantages of nanoemulsion technology, our study underscores the potential of DES-based formulations to promote drug delivery systems across a variety of therapeutic applications.

Nanoparticles (NPs) preparation is limited to an exclusive use in batch processes and small-scale formulations. The use of membranes as high-performance micromixers is expected to open new scenarios to overcome limitations of conventional nanoprecipitation system such as stirred tank (ST) nanoprecipitation. The ability of the porous membrane to add uniformly one phase to another and govern their mixing at the membrane interface seems to be an important parameter for obtaining uniform NPs. Inorganic membranes (pore size of 1 μm) were used to carry out membrane nanoprecipitation (MN) to form Zein nanoparticles (ZNPs) at pores level by non-solvent induced phase separation. A systematic study of the preparation of ZNPs in the ST and MN systems was carried out to establish the Ouzo diagram. The influence of zein concentration and solvent to non-solvent ratio on the size and size distribution of ZNPs was also investigated. A wider stable Ouzo zone was obtained with MN than with the ST process. ZNPs size increased from 100 nm up to 700 nm, while maintaining low polydispersity index (PDI < 0.2). The results demonstrate the suitability of MN for the continuous production of ZNPs and open the possibility of scaling up the nanoprecipitation process.

The production of polymeric particles is the subject of extensive research in various fields and the interest in this area extends to the development of new sustainable production processes. The use of membrane technology has enabled the redesign of many traditional production processes with enormous impact in terms of product quality, reduction of energy consumption, high efficiency, productivity and reproducibility. In the present work, two alternative methodologies for the production of polycaprolactone (PCL) particles based on the use of membrane processes were investigated: i) membrane emulsification (ME) combined with solvent diffusion and ii) membrane nanoprecipitation (MN). ME/solvent diffusion is a widely applied technique for the production of microparticles, but its use for nanosized particles is still limited. On the other hand, MN is currently being investigated for its potentiality in the production of nanoparticles.In the present work, the performance of the two processes is compared in terms of: i) product quality (highly monodisperse particles in the nanometers range of size, ii) maximum productivity (expressed as mass of particles produced over time) under mild operating conditions (reduced mechanical stress), iii) environmental impact (assessed on the basis of the metrics established by the Green Aspiration Level (GAL)).

Ionotropic gelation (IG) is a highly attractive method for the synthesis of natural water-soluble polymeric nanoparticles (NPs) and sub-micron particles (sMP) due to its relatively simple procedure and the absence of organic solvents. The method involves the electrostatic interaction between two ionic species of opposite charge. Although it is well studied at the laboratory scale, the difficulty to achieve size control in conventional bench-top process is actually a critical aspect of the technology. The aim of this work is to study the membrane dispersion technology in combination with IG as a suitable scalable method for the production of chitosan sub-micron particles (CS-sMPs).The two phases, one containing chitosan (CS) and the other containing sodium tripolyphosphate (TPP), were put in contact using a tubular hydrophobic glass membrane with a pore diameter of 1 & mu;m. TPP (dispersed phase) was permeated through the membrane pores into the lumen side along which the CS solution (the continuous phase) flowed in batch recirculation or continuous single-pass operation mode. The influence of chemical variables (i.e. pH, concentration and mass ratio of polyelectrolyte species, emulsifier) and fluid-dynamic parameters (i.e. polyelectrolyte solution flow rate and their relative mass ratio) was studied to precisely tune the size of CSPs.

Microfiltration (MF) is recognized as a promising green process that can efficiently treat different types of wastewater. However, the efficiency, economic viability and technological feasibility of MF can be severely affected by fouling. The occurrence of specific fouling mechanisms depends on the specific membrane materials and related physico-chemical properties, characteristics of solutes present in the feeding solution, and operating conditions. The present study aims at evaluating the extent of membrane fouling and its impact on flux decline during olive mills wastewater (OMWW) microfiltration in a semi-pilot plant. The possibility to restore the initial membrane performance was evaluated in terms of cleaning efficiency (CE). OMWW MF was carried out using both polymeric (polyvinylidene fluoride, PVDF) and ceramic membranes (zirconia and alpha-alumina) at trans -membrane pressures (TMP) up to 1.7 bar. The highest permeate flux was obtained using alpha-alumina membrane (35.4 +/- 1.6 L m(- 2) h(-1) at 1.2 bar TMP), the zirconia membrane, despite a slight decrease in flux compared to the alumina membrane, allowed the better restoration of the initial water permeability after cleaning procedures (CE =74 %). PVDF membrane was found to be the least suitable for treatment of OMWW due to low permeate flux (5.3 L m(-2) h(-1) at 1.2 bar TMP) and the inability to restore initial water permeability (CE = 8 %). Each peculiar fouling mechanism was estimated by fitting the experimental filtration data to the linearized equations of the Hermia model, single and multistage, corresponding to pore blocking (complete, intermediate and standard) and cake formation. Results indicated that for alpha-alumina and zirconia membranes the dominant fouling mechanism was cake layer formation. For the PVDF membrane Hermia multistage model revealed that the initial flux decline is appropriately described by standard pore blocking whereas after the first 10 min of operation the fouling mechanism switched to cake layer formation.

The agri-food sector generates substantial quantities of waste material on farm and during the processing of these commodities, creating serious social and environmental problems. However, these wastes can be resources of raw material for the production of valuable chemicals with applications in various industrial sectors (e.g., food ingredients, nutraceuticals, bioderived fine chemicals, biofuels etc.). The recovery, purification and biotransformation of agri-food waste phytochemicals from this microbial spoilage-prone, complex agri-food waste material, requires appropriate fast pre-treatment and integration of various processes. This review provides a brief summary and discussion of the unique advantages and the importance of membrane technology in sustainable recycling of phytochemicals from some of the main agri-food sectors. Membrane-based pressure -driven processes present several advantages for the recovery of labile compounds from dilute streams. For example, they are clean technologies that can operate at low temperature (20–60 °C), have low energy requirements, there is no need for additional chemicals, can be quite automated and electrifiable, and have low space requirements. Based on their permselective properties based on size-, shape-, and charge-exclusion mechanisms, membrane-based separation processes have unpaired efficiency in fractionating biological components while presenting their properties. Pressure-driven membrane processes, such as microfiltration (MF), ultrafiltration (UF) and nanofiltration (NF), as well as other advanced membrane-based processes such as membrane bioreactors (MBR), membrane emulsification (ME) and membrane distillation (MD), are presented. The integration of various membrane technologies from the initial recovery of these phytochemicals (MF, UF, NF) to the final formulation (by ME) of commercial products is described. A good example of an extensively studied agri-food stream is the olive processing industry, where many different alternatives have been suggested for the recovery of biophenols and final product fabrication. Membrane process integration will deliver in the near future mature technologies for the efficient treatment of these streams in larger scales, with direct impact on the environmental protection and society (production of compounds with positive health effects, new job creation, etc.). It is expected that integration of these technologies will have substantial impact on future bio-based societies over forthcoming decades and change the way that these chemicals are currently produced, moving from petrochemical-based linear product fabrication to a sustainable circular product design based in agri-food waste biomass.

α-tocopherol (α-T) has the highest biological activity with respect to the other components of vitamin E; however, conventional formulations of tocopherol often fail to provide satisfactory bioavailability due to its hydrophobic characteristics. In this work, α-tocopherol-loaded nanoparticles based on chitosan were produced by membrane emulsification (ME). A new derivative was obtained by the cross-linking reaction between α-T and chitosan (CH) to preserve its biological activity. ME was selected as a method for nanoparticle production because it is recognized as an innovative and sustainable technology for its uniform-particle production with tuned sizes and high encapsulation efficiency (EE%), and its ability to preserve the functional properties of bioactive ingredients operating in mild conditions. The reaction intermediates and the final product were characterized by 1HNMR, Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), while the morphological and dimensional properties of the nanoparticles were analyzed using electronic scanning microscopy (SEM) and dynamic light scattering (DLS). The results demonstrated that ME has high potential for the development of α-tocopherol-loaded nanoparticles with a high degree of uniformity (PDI lower than 0.2), an EE of almost 100% and good mechanical strength, resulting in good candidates for the production of functional nanostructured materials for drug delivery. In addition, the chemical bonding between chitosan and α-tocopherol allowed the preservation of the antioxidant properties of the bioactive molecule, as demonstrated by an enhanced antioxidant property and evaluated through in vitro tests, with respect to the starting materials.

α-Tocopherol-loaded nanoparticles based on chitosan have been produced by using two different methods: microemulsification and membrane emulsification combined with cross-linking reaction. The membrane emulsification is an innovative technology for the production of uniform particles with tuned size and high encapsulation efficiency (EE%) able to operate in mild operative conditions in order to preserve the functional properties of bioactive ingredients. Due to the intrinsic functional properties of the individual materials (i.e. antioxidant, emollient, immunosuppressive activity) and considering the positive synergy resulting from their combined formulation the produced nanoparticles can be used for the topical treatment of psoriasis in order to overcome the side effects typical of a systemic therapy. The microemulsification was used as technique to prepare in a conventional way the α-tocopherol-loaded nanoparticles that was compared to those obtained by means of membrane emulsification method. The membrane-based technology demonstrated high potential for the development of α-Tocopherol-loaded nanoparticles with high degree of uniformity (PDI lower than 0.2), EE of almost 100% and good mechanical strength. The nanoparticles have been also used for cyclosporine encapsulation (EE = 65%) demonstrating their possible use as drug delivery systems for psoriasis treatment taking advantage of both the properties of the newly synthesized material and the technology used for the preparation of the carrier. The membrane emulsification technique results a good candidate for the production of functional nanostructured materials for drug delivery.

The high potential of nanomaterials in different fields, from aerospace applications to healthcare technology and medical diagnostics, requires new production methods to build and control particle structure properties in large-scale manufacturing with lower energy and material consumption to enable wide penetration of the industrial sector. Membrane technology is an extremely promising, environmentally friendly and scalable method for nanoparticles (NPs) production with tremendous impact in terms of formulation quality, energy consumption reduction and waste minimization. Among the membrane-based processes for particles production, membrane nanoprecipitation (MN) is emerging as a scalable and efficient method for particles engineering at nanoscale. This review provides a detailed analysis of the current developments and efforts in the application of membrane technology for the fabrication of NPs (polymeric, liposomes and drug nanocrystals) by nanoprecipitation. In the MN process, two miscible phases (called “solvent” - which contains a solute - and “non-solvent” - which does not dissolve the solute) are separated by a membrane and meet at the pore mouth, where they mix and cause precipitation of the solute in the form of NPs. This review aims to highlight the mechanism of MN and identify the parameters that control the process. The influence of chemical parameters (such as type of solvent, non-solvent and solute), fluid-dynamic parameters (flux, wall shear stress, flow mode of operation) and membrane parameters (pore size, membrane surface wettability, pore shape and interpore distance) on the resulting nanoparticle size and size distribution was analysed. The performance of MN and other methods for producing NPs (mixing devices and microfluidics) was compared. The emerging studies on nanoprecipitation combined with membrane technology open a new window for the application of membrane science in the production of NPs to achieve a fine control of the mixing process with good accuracy and high productivity.

The use of membranes as dispersing tools opens new development perspectives to the traditional nanoprecipitation technique by overcoming one of its major limitations, related to its exclusive use in batch processes and for small scale formulations. In this work the suitability of membrane nanoprecipitation for the formulation of uniform hydrogel nanoparticles (H-NPs) based on polyvinyl alcohol (PVA) in a continuous process has been demonstrated. This is a challenging formulation even for the traditional nanoprecipitation process, which has been well studied mainly for polymers of a hydrophobic nature. A systematic study of the phase composition and operating conditions of membrane nanoprecipitation allowed us to clarify the influence of the components involved in PVA nanoprecipitation promoted by non-solvent-induced phase separation and to identify the conditions to ensure the continuous production of uniform PVA hydrogel NPs. The size of PVA-H-NPs was tailored by tuning the solvent, non-solvent (dispersing medium), PVA concentration and volumetric ratio between solvent and non-solvent. The use of a porous membrane to assist nanoprecipitation in the batch allowed us to demonstrate that nanoprecipitation was not influenced by flux through the membrane or wall shear stress, but mainly by the solvent/non-solvent volumetric ratio. The obtained knowledge permitted to set up the membrane system for the continuous preparation of PVA-H-NPs, which was carried out in single-pass cross-flow mode. To the best of our knowledge, this is the first preparation of PVA-H-NPs in a continuous membrane nanoprecipitation process. Compared to batch nanoprecipitation, an order of magnitude higher mass productivity was achieved.

Multiphase bioreactors using interfacial biocatalysts are unique tools in life sciences such as pharmaceutical and biotechnology. In such systems, the formation of microdroplets promotes the mass transfer of reagents between two different phases, and the reaction occurs at the liquid–liquid interface. Membrane emulsification is a technique with unique properties in terms of precise manufacturing of emulsion droplets in mild operative conditions suitable to preserve the stability of bioactive labile components. In the present work, membrane emulsification technology was used for the production of a microstructured emulsion bioreactor using lipase as a catalyst and as a surfactant at the same time. An emulsion bioreaction system was also prepared by the stirring method. The kinetic resolution of (S,R)-naproxen methyl ester catalyzed by the lipase from Candida rugosa to obtain (S)-naproxen acid was used as a model reaction. The catalytic performance of the enzyme in the emulsion systems formulated with the two methods was evaluated in a stirred tank reactor and compared. Lipase showed maximum enantioselectivity (100%) and conversion in the hydrolysis of (S)-naproxen methyl ester when the membrane emulsification technique was used for biocatalytic microdroplets production. Moreover, the controlled formulation of uniform and stable droplets permitted the evaluation of lipase amount distributed at the interface and therefore the evaluation of enzyme specific activity as well as the estimation of the hydrodynamic radius of the enzyme at the oil/water (o/w) interface in its maximum enantioselectivity.

Drug-loaded poly (vinyl alcohol) (PVA)-based microparticles have been synthetized by using membrane emulsification and chemical cross-linking. The encapsulation of two water-soluble molecules, catechol (CA) and diclofenac sodium (DS), has been considered as case studies. PVA hydrogels have been recognized as promising biomaterials and suitable candidates for drug delivery. However, the encapsulation of hydrophilic, low molecular weight drugs in particulate materials is currently an ambitious goal. The purpose of this work was to develop high-drug loading systems for hydrophilic molecule delivery based on uniformly distributed particulate carriers. Membrane emulsification has been used as advanced manufacturing method to design drug-loaded PVA microparticles with target properties in terms of particle size, particle size distribution, structure and functional activity. A special emphasis is laid on the important factors that contribute to tune the structured properties of microparticles, encapsulation efficiency/drug loading and drug delivery. In particular, the influence of emulsification method (membrane and homogenizing approaches), phase compositions (PVA concentration, drug concentration, physicochemical properties of drug), cross-linking reaction conditions (cross-linking agent concentration, acidic media) has been studied. Finally, the potential of PVA-based microparticles as drug delivery carriers as well as their in vitro cytotoxicity have been evaluated.

Membrane emulsification and membrane nanoprecipitation are contactor devices that permit the design and tuning of micro/nano particles (emulsions, solid lipid, and polymeric particles). In these processes, porous membranes made of hydrophilic or hydrophobic materials are needed to formulate oil-in-water (O/W) or water-in-oil (W/O) emulsions, respectively. The membrane emulsification method compared to the traditional emulsification technique offers more precise control of particle size and particle size distribution using mild operation conditions. This chapter presents an overview of membrane emulsification and membrane nanoprecipitation principles and mechanisms. The main process and phases parameters, as well as membrane properties for the membrane emulsification and membrane nanoprecipitation are highlighted. The membranes used in membrane emulsification and membrane nanoprecipitation and the related formulations produced are also summarized.