Membrane Emulsification Technology Research Articles

Preparation and in vitro/in vivo evaluation of uniform-sized Goserelin-loaded sustained release microspheres

Sustained release microspheres loaded with goserelin are regarded as a promising candidate for treating prostate cancer and other sex hormone diseases. However, their widespread adoption has been hindered by issues such as wide particle size distribution and unstable release characteristics. To address these challenges, we employed a combination of the solid-in-oil-in-water microspheres preparation approach (S/O/W) and innovative premix membrane emulsification technology and deeply investigated the effects of four key parameters on the loaded performance of microspheres and the microscopic mechanisms behind them. With this approach, we successfully produced goserelin-loaded sustained release microspheres of narrow particle size distribution (Span 0.642), remarkable encapsulation efficiency (DL = 4.23 %, EE = 93.98 %), low initial burst release (about 0.50 % within 2 h), and compatibility with small injection needles (23-G, inner diameter 0.33 mm, outer diameter 0.64 mm, maximal force 59 N). In the animal model(administered dose, 2.4 mg·Kg−1), goserelin long-acting sustained release microspheres sustained release for over 32 days, maintaining effective concentrations above 2 ng·mL−1, and effectively reduced serum testosterone concentrations to castration levels (<1.0 ng·mL−1) by day 4, maintaining this inhibition for up to 21 days, exhibiting comparable efficacy to the positive control group. In vivo release kinetics analysis revealed that goserelin-loaded sustained release microspheres exhibited a release pattern dominated by diffusion with corrosion assistance in vivo. In summary, the systematic and comprehensive evaluation of uniform-sized goserelin-loaded sustained release microspheres has highlighted their excellent translational potential, and the study herein may provide new strategies and ideas for the development of microsphere dosage forms.

Oriented Interpenetrating Capillary Network with Surface Engineering by Porous ZnO from Wood for Membrane Emulsification.

Membrane emulsification technology has garnered increasing interest in emulsion preparation due to controllable droplet size, narrower droplet size distribution, low energy consumption, simple process design and excellent reproducibility. Nevertheless, the pore structure and surface engineering in membrane materials design play a crucial role in achieving high-quality emulsions with high throughput simultaneously. In this work, an oriented interpenetrating capillary network composed of highly aligned and interconnected wood cell lumens has been utilized to fabricate an emulsion membrane. A novel honeycomb porous ZnO layer obtained by a seed prefabrication-hydrothermal growth method was designed to reconstruct wood channel surfaces for enhanced microfluid mixing. The results show that through the unique capillary mesh microstructure of wood, the emulsion droplets were smaller in size, had narrower pore-size distribution, and were easy to obtain under high throughput conditions. Meanwhile, a well-designed ZnO layer could further improve the emulsion quality of a wood membrane, while the emulsifying throughput is still maintained at a higher level. This demonstrates that the convection process of the microfluid in these wood capillary channels was intensified markedly. This study not only develops advanced membrane materials in emulsion preparation, but also introduces a brand-new field for functional applications of wood.

Enhanced micro-explosion to improve the yield of light oil in catalytic cracking of water-in-heavy oil emulsion prepared by continuous membrane emulsification

Membrane emulsification provides new ideas for improving the atomization performance of high viscosity heavy oil in catalytic cracking process, thereby improving the distribution of catalytic cracking products. A comprehensive understanding of the micro-explosion characteristics and catalytic cracking of low water content heavy oil emulsion is the key to the application of membrane emulsification technology in heavy oil catalytic cracking process. Therefore, different water droplet sizes and water content of heavy oil emulsion were controllably prepared by continuous membrane emulsification, and their micro-explosion characteristics and catalytic cracking performance were investigated. The evaporation of heavy oil emulsion droplets (water content over 3 vol%) only underwent the heat transfer stage and the fluctuating evaporation stage due to the strong micro-explosion. The micro-explosion delay time of emulsion droplets decreased from 2.631 to 0.434 s/mm2 with increased temperature (300–600 ℃), increased from 0.645 to 1.042 s/mm2 with increased water content (1–5 vol%), and increased from 0.642 to 1.237 s/mm2 with increased average droplet size (1.80–14.6 μm). The child droplets generated after micro-explosion were characterized, and the different heating behaviors were quantitatively distinguished by the average size of the child droplets. Additionally, the micro-explosion performance (i.e. child droplets size and strong micro-explosion probability) of emulsion droplets improved with increasing water content and average water droplet size, while it initially decreased and then increased when the temperature increased. Furthermore, the improvement of micro-explosion performance by membrane emulsification can increase the yield of light oil (up to a maximum increase of 10.82 %) and reduce the yield of coke (up to a maximum decrease of 5.99 %) in the heavy oil emulsion catalytic cracking.

Hydrophilic TiO2@MXene membrane for direct generation of monodisperse submicron water-in-diesel emulsion and its microexplosion performance

Hydrophilic membrane interfaces, especially that of particle-packed ceramic membranes, are generally not suitable for use as emulsification media for generating monodisperse water-in-oil emulsions. This is because their short adjacent pore distances tend to cause droplet coalescence. In this study, a facile in situ oxidation strategy was proposed to develop ceramic-based hydrophilic TiO2@MXene membranes for directly generating monodisperse submicron water-in-diesel emulsions using membrane emulsification technology at room temperature. Through the in situ oxidation process, numerous TiO2 nanoparticles were grown on the surface of MXene nanosheets to form a novel TiO2@MXene composite structure with a membrane pore size of 12.2 nm. This structure is characterized by abundant transport channels, remarkably robust stability, and high water permeance of 154.8 L m−2 h−1 bar−1. Because of the long horizontal distance between adjacent nanosheets and the substantially reduced transport resistance, water droplets can roll smoothly along the TiO2@MXene nanochannels and then converge with the diesel, thus reducing the risk of emulsion coalescence. The mean droplet size of the emulsions can be controlled from ∼100 to 500 nm by regulating the emulsification conditions. The optimal emulsions exhibited excellent monodispersity with an average droplet size of 157.2 nm and possessed relatively excellent long-term stability (up to 45 days). Moreover, the emulsions showed a positive microexplosion phenomenon during heating. The maximum microexplosion strength of the emulsions reached 6.31 m s−1 (at 20% water content), which provides a reliable theoretical basis for research on emulsified diesel as an alternative to traditional fuels.

A review of recent research and development on GLP-1 receptor agonists-sustained-release microspheres.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in treating type 2 diabetes (T2D). However, owing to their limited oral bioavailability, most commercially available GLP-1 RAs are administered through frequent subcutaneous injections, which may result in poor patient compliance during clinical treatment. To improve patients' compliance, sustained-release GLP-1 RA-loaded microspheres have been explored. This review is an overview of recent progress and research in GLP-1 RA-loaded microspheres. First, the fabrication methods of GLP-1 RA-loaded microspheres including the coacervation method, emulsion-solvent evaporation method based on agitation, premix membrane emulsification technology, spray drying, microfluidic droplet technology, and supercritical fluid technology are summarized. Next, the strategies for maintaining GLP-1 RAs' stability and activity in microspheres by adding additives and PEGylation are reviewed. Finally, the effect of particle size, drug distribution, the internal structure of microspheres, and the hydrogel/microsphere composite strategy on improved release behavior is summarized.

Local Destruction of Tumors for Systemic Immunoresponse: Engineering Antigen-Capturing Nanoparticles as Stimulus-Responsive Immunoadjuvants.

Immunotherapy has established a new paradigm for cancer treatment and made many breakthroughs in clinical practice. However, the rarity of immune response suggests that additional intervention is necessary. In recent years, it has been reported that local tumor destruction (LTD) can cause cancer cell death and induce an immunologic response. Thus, the combination of immunotherapy and LTD methods will be a promising approach to improve immune efficiency for cancer treatment. Herein, a nanobiotechnology platform to achieve high-precision LTD for systemic cancer immunotherapy has been successfully constructed. Possessing radio-sensitizing and photothermal properties, the engineered immunoadjuvant-loaded nanoplatform, which could precisely induce radiotherapy (RT)/photothermal therapy (PTT) to eliminate local tumor and meanwhile lead to the release of tumor-derived protein antigens (TDPAs), has been facilely fabricated by commercialized SPG membrane emulsification technology. Further on, the TDPAs could be captured and form personal nanovaccines in situ to serve as both reservoirs of antigen and carriers of immunoadjuvant, which can effectively improve the immune response. The investigations suggest that the combination of RT/PTT and improved immunotherapy using adjuvant-encapsulated antigen-capturing nanoparticles holds tremendous promise in cancer treatments.

CdSe/ZnS quantum dot-encoded maleic anhydride-grafted PLA microspheres prepared through membrane emulsification for multiplexed immunoassays of tumor markers.

Early diagnosis of tumor markers is of great importance for the successful treatment of cancer. As a high-throughput and high-sensitivity detection technology, liquid suspension biochips based on quantum dot (QD) encoded microspheres have been widely used in the immunodetection of tumor markers. In this work, maleic anhydride grafted PLA (PLA-MA) microspheres based on quantum dot encoding were used as carriers for liquid phase suspension biochips for the immunoassay of tumor markers. PLA-MA fluorescent beads are prepared by embedding CdSe/ZnS quantum dots in PLA-MA using Shirasu porous glass (SPG) membrane emulsification technology, which has high fluorescence intensity, good stability, and good dispersion. Fluorescent immunoassays on dipsticks found that PLA-MA microspheres have high biological activity and good stability, which is conducive to immunoassays. Based on this, using the characteristics of CdSe/ZnS quantum dots and flow cytometry, monochromatic and two-color coding methods were developed, and 9 distinguishable coding beads were prepared. The results showed that PLA-MA fluorescent microspheres exhibited good biocompatibility, stable coding signals, low background noise, and low detection limits when performing quaternary immunoassays on tumor markers CA125, CA199, CA724, and CEA by CdSe/ZnS QD-encoded PLA-MA microsphere binding flow cytometry.

Comparison between Lipase Performance Distributed at the O/W Interface by Membrane Emulsification and by Mechanical Stirring.

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.

Generation of magnesium enriched water-in-oil-in-water food emulsions by stirred cell membrane emulsification

This study has for the first time shown that complex food emulsifiers such as starch and protein can be applied to produce stable w/o/w emulsions with the membrane emulsification technology. Using a microporous metal membrane with a 20 μm pore size, 2% of polyoxyethylene (20) sorbitan monolaurate (Tween 20), 4% of octenyl succinic anhydride (OSA) starch or 1.5% of pea protein isolate (PPI) in the external water phase respectively was the minimum concentration necessary to stabilise the w/o/w droplets. Uniform with a span as low as 0.45 and for at least 13-day stable w/o/w emulsions of droplets between 35 and 320 μm were obtained. The release of a magnesium tracer from the internal water phase of xanthan gum-thickened w/o/w emulsions, when OSA starch and PPI were used, was found to be limited to around 3% after 13-day storage. However, w/o/w emulsions stabilised with Tween 20 were less stable with magnesium showing a release of 27% on day 13.

Monomer-in-water miniemulsions by membrane emulsification

Commercial products of miniemulsion polymerization are still scarce, and one of the major challenges for industrial implementation is the miniemulsification step. The aim of this work is to introduce the membrane emulsification technology as a robust and low energy alternative. The proposed system allows the production of monomer-in-water miniemulsions with droplet sizes of around 300nm and moderate distributions for up to 30wt% of methyl methacrylate phase in a quick and simple way. Thus, the membrane emulsification technology can become an excellent approach for the production of miniemulsions for polymerization. The emulsifying power of four pumps, used in the membrane emulsification setups, was also studied and it was shown that in most cases, with the single use of the pumps, emulsions with broad distributions were produced.

Porous Nanohydroxyapatite/Collagen Scaffolds Loading Insulin PLGA Particles for Restoration of Critical Size Bone Defect.

Insulin is considered to be a classical central regulator of energy homeostasis. Recently, the effect of insulin on bone has gained a lot of attention, but little attention has been paid to the application in bone tissue engineering. In this study, porous nanohydroxyapatite/collagen (nHAC) scaffolds incorporating poly lactic-co-glycolic acid (PLGA) particles were successfully developed as an insulin delivery platform for bone regeneration. Bioactive insulin was successfully released from the PLGA particles within the scaffold, and the size of the particles as well as the release kinetics of the insulin could be efficiently controlled through Shirasu porous glass premix membrane emulsification technology. It was indicated that the nHAC/PLGA composite scaffolds possessed favorable mechanical and structural properties for cell adhesion and proliferation, as well as the differentiation into osteoblasts. It was also demonstrated that the nHAC/PLGA scaffolds implanted into a rabbit critical-size mandible defect possessed tissue compatibility and higher bone restoration capacity compared with the defects that were filled with or without nHAC scaffolds. Furthermore, the in vivo results showed that the nHAC/PLGA scaffolds which incorporated insulin-loaded microspheres with a size of 1.61 μm significantly accelerated bone healing compared with two other composite scaffolds. Our study indicated that the local insulin released at the optimal time could substantially and reproducibly improve bone repair.

Microencapsulation Analysis Based on Membrane Technology: Basic Research of Spherical, Solid Precursor Microcapsule Production

The objective of the proposed investigation was to synthesis of precursor oil-carbohydrate microcapsule, suspended in water by membrane emulsification technology. To select the carrier material of precursor microcapsules, four different carbohydrates (maltodextrin, hydroxypropyl cellulose, potato starch and corn starch) were tested. Preliminary, zeta-potential, molecular weight and particle size of individual carbohydrate were estimated by Malvern Zetasizer instrument. Based on the results of the preliminary characterizations, maltodextrin was selected to carry out subsequent experiments. Maltodextrin suspended in oil and water were considered as dispersed phase and continuous phase respectively. An attempt has been made to remove the water, as well as to recover the microcapsules. It was observed that average particle size of synthesized microcapsule is 6.9 μm and stability of the microcapsule is at least 6 weeks.

Polymeric microspheres preparation by membrane emulsification-phase separation induced process

Uniform Polyethersulfone (PES) microspheres of target size in the range of 30–60µm were successfully prepared by combining membrane emulsification technology and phase separation induced process in one step. An emulsion is generated by injecting the polymeric solution through a microporous membrane into the continuous phase which allows also the phase separation induced process and precipitation of the polymer (coagulation bath). Therefore, the droplets formation and solidification occur in a single step. Furthermore, the preparation of non-aqueous (O/O) emulsions by membrane emulsification as well as the preparation of polymeric microspheres by non-solvent induced phase separation has never been reported previously. The effect of continuous phase-coagulation bath composition, hydrophobic emulsifier, dispersed phase flux and shear stress on size and uniformity of PES microspheres has been investigated. Key factors in microspheres production by membrane emulsification and phase separation induced process mechanism include the solvent/non-solvent system type, non-solvent composition and O/O interface composition. Polymeric microspheres with spherical morphology have been produced by tailoring such key factors.

New developments for the controlled fabrication of microstructured multiphase bioreactor using membrane emulsification technology

New developments for the controlled fabrication of microstructured multiphase bioreactor using membrane emulsification technology

Performance of slotted pores in particle manufacture using rotating membrane emulsification

This paper addresses the use of different slotted pores in rotating membrane emulsification technology. Pores of square and rectangular shapes were studied to understand the effect of aspect ratio (1–3.5) and their orientation on oil droplet formation. Increasing the membrane rotation speed decreased the droplet size, and the oil droplets produced were more uniform using slotted pores as compared to circular geometry. At a given rotation speed, the droplet size was mainly determined by the pore size and the fluid velocity of oil through the pore (pore fluid velocity). The ratio of droplet diameter to the equivalent diameter of the slotted pore increased with the pore fluid velocity. At a given pore fluid velocity and rotation speed, pore orientation significantly influences the droplet formation rate: horizontally disposed pores (with their longer side perpendicular to the membrane axis) generate droplets at double the rate of vertically disposed pores. This work indicates practical benefits in the use of slotted membranes over conventional methods.

Preparation and characterisation of a novel buoyancy and refractive index matched oil-in-water emulsion

We report a novel oil-in-water emulsion that is both buoyancy and refractive index matched. The dispersion is created using low-shear cross-flow membrane emulsification technology with a discrete phase comprising a mixture of n-hexane and the perfluorinated oil tetradecafluorohexane, in the form of FC-72. Three-dimensional confocal laser light imaging of a bulk-aggregated emulsion is demonstrated, showing explicit droplet-level detail of the emulsion interior. Magnetic resonance microscopy with a spatial resolution of tens of microns is also described. The proximity of a liquid–liquid binodal in the oil mixture can give rise to a ternary phase separation reminiscent of an O/O/W emulsion.

Particle control of emulsion by membrane emulsification and its applications

Particle-size control of emulsion is very important for maintaining stability and giving emulsions new functional roles. Porous glass membrane, prepared by phase separation of a glass composition, is available as an emulsifying element, from which, one can obtain monodispersed emulsion with different particle sizes, and useful water/oil/water (W/O/W) emulsion in very high yield. The authors have called this new technology ‘membrane emulsification’. Applications of membrane emulsification technology to drug delivery systems were carried out under cooperative research with Miyazaki Medical College. It was found that the clinical administration of a W/O/W drug emulsion that encapsulated an anticancer drug in its inner droplets was surprisingly effective for both terminal and multiple nodules of hepatocellular carcinoma when the drug was injected to damaged liver through a catheter inserted in the hepatic artery. Other applications have been tried and developed elsewhere.