SPG Membrane Research Articles

Development of erythrocyte-mimetic PFOB/PDMS thermoplastic elastomer core-shell microparticles via SPG membrane emulsification

Erythrocyte-mimetic perfluorooctylbromide (PFOB)/polydimethylsiloxane (PDMS) thermoplastic elastomer core-shell microparticles were fabricated (for the first time) via Shirasu porous glass membrane emulsification (SPG ME) with evaporation-induced phase separation (EIPS). The resulting micro-sized core-shell particles showed a spontaneously concave shape without a subsequent deformation process such as organic solvent immersion or temperature variations. It replicated the healthy human erythrocyte morphology. In addition, their sizes and morphologies could be controlled by varying the pore size and dispersed-phase composition of the SPG membrane. The diameters of the precisely controlled particles were similar to those of human blood cells (9.6 ± 1.9 μm). The microcompression test revealed a high deformability of the particles owing to both softness of the PDMS-TPE shell and their core-shell structure. The PDMS-based materials displayed a high oxygen permeability, and PFOB displayed a high oxygen solubility. Finally, the oxygen transportation function was evaluated using oxygen tension-responsive HeLa cells (hr-HeLa) under hypoxic conditions (5% O2). This demonstrated the effectiveness of PFOB/PDMS-TPE microparticles as artificial oxygen carriers in various biomedical applications such as tissue engineering.

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.

An injectable mPEG-PDLLA microsphere/PDLLA-PEG-PDLLA hydrogel composite for soft tissue augmentation

Injectable filling material is a simple and efficient method for soft tissues reconstruction and is extremely popular in not only plastic surgery but also cosmetic industry. However, there is a lack of soft tissue fillers with perfect performance on the market currently. Here, we constructed a new microsphere/hydrogel composite and evaluated its potential as a candidate for soft tissue augmentation. mPEG-PDLLA microspheres were prepared by utilizing a SPG membrane emulsifier which endowed microspheres with good sphericity and particle size uniformity. PDLLA-PEG-PDLLA hydrogel which shared the same component with the mPEG-PDLLA copolymer acted as a carrier and fixed the microspheres at the injected sites. The mPEG-PDLLA microsphere/PDLLA-PEG-PDLLA hydrogel composite was flowable in room temperature and transformed into gel after being heated to body temperature. This feature is convenient for subcutaneous filling. In vivo assessment on mice showed good safety profile of the composite. Moreover, the density of collagen fibers increased over 13 weeks. Overall, this biocompatible microsphere/hydrogel composite involves simple component and no extra crosslinking agents, and has the ability to stimulate collagen production, thus, may be a candidate for soft tissue augmentation.

Preparation of A/O/W Emulsion by Using SPG Membrane

Preparation of A/O/W Emulsion by Using SPG Membrane

Facile fabrication of PEG-coated PLGA microspheres via SPG membrane emulsification for the treatment of scleroderma by ECM degrading enzymes

We developed a facile fabrication method for preparing poly(ethylene glycol)(PEG)-coated poly (lactic-co-glycolic acid) (PLGA) microspheres with homogeneous size distribution via a combination of mPEG-b-PLGA and Shirasu Porous Glass membrane emulsification. Subsequently, extracellular matrix (ECM) degrading enzymes, collagenase (COLase) or hyaluronidase (HAse) were loaded into the microspheres. The obtained microspheres exhibited a sustained release of COLase or HAse over 10 days. The degradation of ECM polymers by the released COLase and HAse was confirmed in vitro. Reversal of established dermal fibrosis via degradation of over-deposited ECM is a promising treatment for scleroderma. The therapeutic effects of COLase- and HAse-loaded PLGA microspheres on scleroderma were evaluated in vivo following their intradermal administration to a bleomycin-induced mice model of scleroderma. COLase- and HAse-loaded PLGA microspheres decreased scleroderma dermal thickness without altering the mechanical properties of skin, whereas the administration of free COLase and HAse solution induced overdecomposition of skin ECM and α-SMA expression. The facile one-pot synthesis of PEG-coated PLGA microspheres with high colloidal stability and narrow size distribution could be employed as a drug carrier for various diseases in future.

Review on SPG membrane emulsification: an efficient approach to prepare uniform microspheric drug carrier

Review on SPG membrane emulsification: an efficient approach to prepare uniform microspheric drug carrier

Optimization and Evaluation of Monodispersed Tetrandrine- Loaded PLA Microspheres Prepared With A SPG Membrane Emulsification Technique

The results of Fourier transform infrared, differential scanning calorimetry and powder X-ray diffraction revealed that tetrandrine would be either molecularly dispersed in the polymer or distributed in an amorphous form

Degradation of Acetic Acid in Water Using Gas-Liquid Plasma with SPG Membrane

Degradation of Acetic Acid in Water Using Gas-Liquid Plasma with SPG Membrane

Synthesis of microcapsules using inverse emulsion periphery RAFT polymerization via SPG membrane emulsification

Synthesis of polymeric capsules with good control over the particle size and size distribution is demonstratedviaa novel approach involving SPG membrane emulsification.

SPG 막유화 및 UV 광중합법에 의해 제조된 PNIPAAm 하이드로젤 입자의 형태학에 관한 연구

Abstract: W/O emulsions were prepared from the aqueous solution containing NIPAAm, MBA, and APS in the continuous phase of toluene and mineral oil mixture with HMP and Span80 by using SPG membrane emul-sification, and followed by the formation of PNIPAAm hydrogel microspheres through UV photopolymerization. As the ratio of mineral oil to toluene increased in the continuous phase, both particle size of the hydrogel in-creased and density of PNIPAAm polymer in the hydrogel particle increased, and which significantly affected swelling/deswelling ratio (V/V o ) with temperature change around VPTT. When the polymerization temperature was below LCST (20°C), PNIPAAm hydrogel showed filled particle morphology; however, it was turned out to hollow particle morphology with thick shell layer with 40°C. Both density of PNIPAAm and gel content of the hydrogel increased with the increase in MBA concentration. Keywords: SPG membrane emulsification, hydrogel, PNIPAAm, LCST 1. 서 론 1) 균일한 입도를 가지는 고분자 입자의 제조방법으로는 분산중합(dispersion polymerization) 및 무유화 에멀젼중합(soap-free emulsion polymerization) 등이 널리 알려져 있으나, 5 µm 이상의 균일한 입도를 가지는 고

Studies on preparation by SPG membrane emulsification method and in vitro characterization of tetradrine-tashionone ⅡA -PLGA composite microspheres

Studies on preparation by SPG membrane emulsification method and in vitro characterization of tetradrine-tashionone ⅡA -PLGA composite microspheres

Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.

The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.

Self-targeted, bacillus-shaped, and controlled-release methotrexate prodrug polymeric nanoparticles for intratumoral administration with improved therapeutic efficacy in tumor-bearing mice.

Poor drug distribution and inefficient drug concentrations within the tumor intracellular environment still limit the therapeutic efficacy of drugs for cancer chemotherapy. Local drug delivery (physical targeting) combined with receptor-mediated drug delivery (chemical targeting) and assistance by a novel shape design is a promising strategy to treat the infiltrating tumor (even those that persist post surgery). In this paper, we prepared dye and methotrexate (MTX) functionalized nanobacilli (MPEG-PLA-MTX-Cy5.5 NB) by a self-assembly technique combined with extrusion through a SPG membrane for intratumoral administration, in which the bacillus-shaped MPEG-PLA-MTX-Cy5.5 NB were armed with a dual-acting MTX that can specifically and efficiently enhance their cellular uptake, while avoiding their dispersion from tumor sites. After intratumoral administration to a H22 xenograft mouse model, the MPEG-PLA-MTX-Cy5.5 NB delivered the drug more effectively to the tumor compared to the MPEG-PLA-Cy5.5 nanospheres (MPEG-PLA-Cy5.5 NSs) and MPEG-PLA-MTX-Cy5.5 nanospheres (MPEG-PLA-MTX-Cy5.5 NSs). Compared to the free MTX and MPEG-PLA-MTX-Cy5.5 NSs, the controlled-release MPEG-PLA-MTX-Cy5.5 NB also significantly inhibited the tumor growth and improved therapeutic efficacy. The platforms are highly convergent, flexible and simplified systems that may serve as guides in the further design of nanoparticles with a revolutionary new shape and function for clinical applications.

In vitro and in vivo study of fluorescent probe PLGA particles prepared by premix membrane emulsification method

Relatively uniform-sized nanoparticles made of poly (lactic-co-glycolic acid) (PLGA) were prepared by premix membrane emulsification method. After the drug loading property was completed, the dynamic tissue distribution of nanoparticles was recorded. With the average particle size and span as indexes, membrane pore size, number of passing membrane times, membrane pressure, volume ratio of oil-water phase and the concentration of poly(vinyl alcohol) (PVA) in external water phase were investigated by single factor test, the optimum preparation technology of blank PLGA nanlparticles was as following: pore size of SPG membrane was 1 μm, membrane pressure was 1. 15 MPa, the number of passing membrane time was 3, the mass fraction of PVA of 2%, volume ratio of oil-water phase of 1 : 5. Prepared nanoparticles were round with smooth surface, the mean diameter was 332.6 nm, span was 0.010, the confocal laser scanning microscope (CLSM) concluded that fluorescent substance is uniform composizion in PLGA nanoparticle, and the in vivo imaging technology in mice include that the nanoparticles show good liver and spleen targeting property.

Mechanistic studies for monodisperse exenatide-loaded PLGA microspheres prepared by different methods based on SPG membrane emulsification

Poly(DL-lactic-co-glycolic acid) (PLGA) microspheres have been widely prepared by many methods, including solvent evaporation, solvent extraction and the co-solvent method. However, very few studies have compared the properties of microspheres fabricated by these methods. This is partly because the broad size distribution of the resultant particles severely complicates the analysis and affects the reliability of the comparison. To this end, uniform-sized PLGA microspheres have been prepared by Shirasu porous glass premix membrane emulsification and used to encapsulate exenatide, a drug for treating Type 2 diabetes. Based on this technique, the influences on the properties of microspheres fabricated by the aforementioned three methods were intensively investigated, including in vitro release, degradation and pharmacology. We found that these microspheres presented totally different release behaviors in vitro and in vivo, but exhibited a similar trend of PLGA degradation. Moreover, the internal structural evolution visually demonstrated these release behaviors. We selected for further examination the microsphere prepared by solvent evaporation because of its constant release rate, and explored its pharmacodynamics, histology, etc., in more detail. This microsphere when injected once showed equivalent efficacy to that of twice-daily injections of exenatide with no inflammatory response.

Processing effects during rotating membrane emulsification

In this study, a rotating membrane emulsification setup incorporating a 6.1μm pore diameter SPG membrane was used to produce O/W emulsions of average droplet sizes between 23.4 and 216.6μm. All emulsions consisted of 10vol% of sunflower oil or silicone oil stabilised by 1wt% Tween 20. The transmembrane pressure (0.1–1.8bar), rotational speeds (100–2000RPM) annular gap width (5–45mm), dispersed and continuous phase viscosity were all investigated as to their effect on emulsion droplet size and dispersed phase flux. Modification of the dispersed phase flow properties alters the droplet size with four regions being suggested; a decrease in size (as droplet coalescence is minimised), a plateau (size-stable zone), a gradual increase in size (due to transfer of mass via droplet neck) and then a rapid increase (due to jetting). The importance of Taylor vortices development was seen with larger droplets formed in their absence; typically at low rotational speeds, narrow vessel diameters and more viscous continuous phases. It was concluded that the flow behaviour of each phase requires careful consideration to understand the likely formation mechanism(s) during operation. Across the pressure and viscosity ranges investigated, the dispersed phase flux ranged between 50 and 12,500Lm−2h−1 and pore activity was within the range of 0.5–2.7%.

Emulsification with microfiltration ceramic membranes: A different approach to droplet formation mechanism

Oil-in-water (O/W) emulsions were prepared by membrane emulsification (ME) in a large scale stirred tank with a submerged cell using flat membranes, and in a cross-flow tubular unit. Results obtained with flat and tubular membranes devices were compared. Common ceramic microfiltration (MF) membranes (ZrO2 supported on TiO2) were used in both cases. The main advantage of these membranes is their low cost compared to others frequently used in ME (SPG membranes), which implies a reduction up to 60%. The effect of operation parameters on droplet size distributions was studied to understand the droplet formation mechanism that takes place in both devices.Monodisperse O/W emulsions were obtained using flat membranes with a droplet-to-pore diameter ratio (Dd/Dp) in the range 2.1–2.9. Span values of 0.58, 0.66 and 0.81 corresponded to membrane pore diameters of 0.45, 0.80, and 1.4μm, respectively, being the active pores fraction in the range of 27–36%. The cross-flow tubular unit allowed for production of monodisperse O/W emulsions but with larger droplet sizes, having droplet-to-pore diameter ratios (Dd/Dp) in the range 3.9–4.7. It was observed a major influence of pore activation by dispersed phase pressure on droplet size distribution.Shear stress had little influence on the droplet size, with both flat and tubular membranes. This suggested that droplet formation mechanism was not shear stress-based. A spontaneous emulsification mechanism was proposed.

Membrane emulsification: A promising alternative for vitamin E encapsulation within nano-emulsion

The purpose of our study was to develop a vitamin E-loaded nano-emulsion which could be a convenient drug carrier to be used for targeting the lungs. The nano-emulsion components (MCT oil and surfactant mixture Tween 80/Brij 35) were selected after solubility studies, and the concentration range was chosen after construction of ternary phase diagrams. For emulsion manufacturing, an SPG membrane emulsification process was developed. Key parameters influence on nano-emulsion characteristics was investigated. It has been established that small droplets and narrow size distribution were favored at low transmembrane pressure, high continuous phase flow rate and high agitation speed. Under optimal conditions, nano-emulsion with a span factor of 0.25±0.01, which meant high monodispersity, and an average size of 78±3nm, was prepared. The high zeta potential of −22.9±0.9mV was sufficient to prevent droplet coalescence. Vitamin E was successfully encapsulated within the optimized nano-emulsion with high entrapment efficiency value (99.7±0.4%). Transmission electron microscopy images revealed spherical-shaped and well-distributed nano-droplets. Additionally, special attention was paid on process reproducibility and preparations stability. Results confirmed the robustness of the optimized membrane emulsification technique which seems to be fast, simple and reliable.

Facile synthesis of hollow polymeric microparticles possessing various morphologies via seeded polymerization

In this paper, hollow poly(styrene-co-divinylbenzene-co-methacrylic acid) microparticles possessing various morphologies were synthesized by a combination of seeded polymerization and SPG membrane emulsification. Three families of polystyrene (PS) microspheres with various molecular weights but similar diameters were fabricated by SPG membrane emulsification. These PS microspheres were used as seeds to investigate the effect of their molecular weight on the phase separation between the PS seeds and microgel-like networks formed during seeded polymerization and on the morphologies of the resultant particles. Our study revealed that three resultant microparticles possessed diameters of ca. 10 μm and hollow cavities. The shell thickness of the particles became thinner as Mw increased from 3.5 × 104 to 28.0 × 104. The morphological evolution of the microparticles during seeded polymerization was monitored, and these results verified the influence of the molecular weight of the PS seeds on the phase separation behavior and hence the morphologies of the resultant particles.

Production of uniform droplets using membrane, microchannel and microfluidic emulsification devices

This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100 l h−1.