Microencapsulation for Pharmaceutical Applications: A Review.

In order to improve bioavailability, stability, control release, and target delivery of active pharmaceutical ingredients (APIs), as well as to mask their bitter taste, to increase their efficacy, and to minimize their side effects, a variety of microencapsulation (including nanoencapsulation, particle size <100 nm) technologies have been widely used in the pharmaceutical industry. Commonly used microencapsulation technologies are emulsion, coacervation, extrusion, spray drying, freeze-drying, molecular inclusion, microbubbles and microsponge, fluidized bed coating, supercritical fluid encapsulation, electro spinning/spray, and polymerization. In this review, APIs are categorized by their molecular complexity: small APIs (compounds with low molecular weight, like Aspirin, Ibuprofen, and Cannabidiol), medium APIs (compounds with medium molecular weight like insulin, peptides, and nucleic acids), and living microorganisms (such as probiotics, bacteria, and bacteriophages). This article provides an overview of these microencapsulation technologies including their processes, matrix, and their recent applications in microencapsulation of APIs. Furthermore, the advantages and disadvantages of these common microencapsulation technologies in terms of improving the efficacy of APIs for pharmaceutical treatments are comprehensively analyzed. The objective is to summarize the most recent progresses on microencapsulation of APIs for enhancing their bioavailability, control release, target delivery, masking their bitter taste and stability, and thus increasing their efficacy and minimizing their side effects. At the end, future perspectives on microencapsulation for pharmaceutical applications are highlighted.

Microencapsulation for Food Applications: A Review.

Food products contain various active ingredients, such as flavors, nutrients, unsaturated fatty acids, color, probiotics, etc., that require protection during food processing and storage to preserve their quality and shelf life. This review provides an overview of standard microencapsulation technologies, processes, materials, industrial examples, reasons for market success, a summary of recent applications, and the challenges in the food industry, categorized by active food ingredients: flavors, polyunsaturated fatty acids, probiotics, antioxidants, colors, vitamins, and others. We also provide a comprehensive analysis of the advantages and disadvantages of the most common microencapsulation technologies in the food industry such as spray drying, coacervation, extrusion, and spray cooling. This review ends with future perspectives on microencapsulation for food applications.

Hand-ground fullerene-nanodiamond composite for photosensitized water treatment and photodynamic cancer therapy.

The unique capability of fullerene (C60) to absorb light and generate reactive oxygen species (ROS) has been extensively studied for photosensitized water treatment and cancer therapy. Various material synthesis strategies have been proposed in parallel to overcome its intrinsic hydrophobicity and to enhance availability in water and physiological media. We present here a strikingly simple approach to make C60 available to these applications by hand-grinding dry C60 powder with nanodiamond (ND) using a mortar and pestle. The resulting ND-C60 composite was found to form a stable aqueous colloidal suspension and efficiently drive photosensitized production of ROS under visible light illumination. ND-C60 rapidly adsorbed and oxidized organic contaminants by photogenerated ROS. In the experiments for photodynamic cancer therapy, ND-C60 was internalized by cancer cells and induced cell apoptosis without noticeable toxicity. Treatment of tumor-bearing mice with ND-C60 and light irradiation resulted in tumor shrinkage and prolonged survival time.

Controlled TiO2 Growth on Reverse Osmosis and Nanofiltration Membranes by Atomic Layer Deposition: Mechanisms and Potential Applications.

Enhancing the chemical and physical properties of the polyamide active layer of thin-film composite (TFC) membranes by surface coating is a goal long-pursued. Atomic layer deposition (ALD) has been proposed as an innovative approach to deposit chemically robust metal oxides onto membrane surfaces due to its unique capability to control coating conformality and thickness with atomic scale precision. This study examined the potential to coat the surface of TFC reverse osmosis (RO) and nanofiltration (NF) membranes via ALD of TiO2. Our results suggest that the optimal ALD conditions, the film growth kinetics, and the depth of deposition are different for RO and NF membranes due to the different diffusive transport of ALD precursors through the membrane pores. The TiO2 coating mainly located at the surface of the RO membrane; in contrast, the TiO2 coating extended to the depth of the NF membrane. The TiO2 coating degraded membrane water permeability and salt rejection beyond 10 cycles of ALD, the condition commonly employed in previous ALD-based membrane modification studies. Instead, this study showed that with fewer than 10 cycles, the TiO2 coating of RO membrane increased the membrane surface charge without negatively impacting water permeability and salt rejection. For the NF membranes, the coating of TiO2 inside their pores led to the tuning of pore sizes and increased the rejection of selected solutes.

Synchronized methylene blue removal using Fenton-like reaction induced by phosphorous oxoanion and submerged plasma irradiation process.

In this study, a combination of phosphorus (PP) oxoanions in a submerged plasma irradiation (SPI) system was used to enhance the removal efficiency of dyes from wastewater. The SPI system showed synergistic methylene blue removal efficiency, due to the plasma irradiation and Fenton-like oxidation. The ferrous ions released from the iron electrode in the SPI system under plasmonic conditions form complexes with the PP anions, which can then react with dissolved oxygen (O2) or hydrogen peroxide (H2O2) via Fenton-like reactions. The experimental results revealed that a sodium triphosphate (TPP) combined SPI system has a higher dye removal efficiency than a tetrasodium pyrophosphate (DP) or a sodium hexametaphosphate (HMP) combined SPI system under similar dissolved iron ion concentrations. To confirm the accuracy of the proposed removal mechanism via Fenton-like oxidation, it was compared to SPI systems under an oxygen environment (TPP/SPI/O2 (k = 0.0182 s-1)) and a nitrogen environment (TPP/SPI/N2 (k = 0.0062 s-1)). The results indicate that the hydroxyl radical (OH) in the TPP/SPI/O2 system is the major oxidant in methylene blue removal, because the dye degradation rates dramatically decreased with the addition of radical scavengers such as tert-butanol (k = 0.0023 s-1) and methanol (k = 0.0021 s-1). On the other hand, no change was observed in the methylene blue removal efficiency of the TPP/SPI/O2 system when it was subjected to a wide range of pHs (3-9). In addition, it was proved that this system could be used to eliminate six different commercial dyes. The results of this study indicated that the TPP/SPI/O2 system is a promising advanced oxidation approach for dye wastewater treatment.

In Situ Healing of Compromised Membranes via Polyethylenimine-Functionalized Silica Microparticles.

Microscale damages to membranes used in large-scale filtration processes for water treatment can result in severe degradation of product water quality. One promising technology to address this issue is in situ healing of compromised membranes via healing agents that are added to the feed side of a membrane system and seal the defect site because of increased hydraulic drag through damage site during filtration. We herein introduce an improved in situ membrane healing method using amine-functionalized silica microparticles that is effective under varying operating conditions, overcoming limitations faced by previous healing agents such as chitosan agglomerates. The silica microparticles are functionalized with branched polyethylenimine (PEI) molecules for efficient interparticle cross-linking with glutaraldehyde. The PEI-decorated silica microparticles (SiO2@PEI MPs) were characterized using scanning electron microscopy, dynamic light scattering, and zeta potential analysis. This study investigates the selective deposition of the SiO2@PEI MPs on the damage area using confocal laser scanning microscopy under variable cross-flow rate (0.5-2.0 L/min) and flushing time (10 to 30 min) conditions. The in situ healing technique recovered the particle rejection of compromised membranes to 99.1% of the original membrane's performance without any flux decline. The results of this study show that the use of SiO2@PEI MPs is a promising and practical approach to ensure membrane process integrity.

Self-Healing Hydrogel Pore-Filled Water Filtration Membranes.

Damages to water filtration membranes during installation and operation are known to cause detrimental loss of the product water quality. Membranes that have the ability to self-heal would recover their original rejection levels autonomously, bypassing the need for costly integrity monitoring and membrane replacement practices. Herein, we fabricated hydrogel pore-filled membranes via in situ graft polymerization of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) onto microporous poly(ether sulfone) (PES) substrates and successfully demonstrated their self-healing ability. Covalent attachment of the hydrogel to the substrate was essential for stable membrane performance. The membranes autonomously restore their particle rejection up to 99% from rejection levels as low as 30% after being physically damaged. We attribute the observed self-healing property to swelling of the pore-filling hydrogel into the damage site, strong hydrogen bonding, and molecular interdiffusion. The results of this study show that hydrogel pore-filled membranes are a promising new class of materials for fabricating self-healing membranes.

Fungal Quorum Quenching: A Paradigm Shift for Energy Savings in Membrane Bioreactor (MBR) for Wastewater Treatment.

In the last 30 years, the use of membrane bioreactors (MBRs) for advanced wastewater treatment and reuse have been expanded continuously, but they still suffer from excessive energy consumption resulting from the intrinsic problem of membrane biofouling. One of the major causes of biofouling in MBRs is bacterial quorum sensing (QS) via N-acylhomoserine lactones (AHLs) and/or autoinducer-2 (AI-2), enabling intra- and interspecies communications, respectively. In this study, we demonstrate that farnesol can substantially mitigate membrane biofouling in a MBR due to its quorum quenching (QQ) activity. When Candida albicans (a farnesol producing fungus) entrapping polymer beads (AEBs) were placed in the MBR, the rate of transmembrane pressure (TMP) rise-up was substantially decreased, even for lower aeration intensities. This finding corresponds to a specific aeration energy savings of approximately 40% (25% through the physical washing effect and a further 15% through the biological QQ effect of AEBs) compared to conventional MBRs without AEBs. A real-time RT-qPCR analysis revealed that farnesol secreted from C. albicans mitigated the biofilm formation in MBRs via the suppression of AI-2 QS. Successful control of biofouling and energy savings through fungal-to-bacterial QQ could be expanded to the plant scale for MBRs in wastewater treatment with economic feasibility.

Decrease of Pseudomonas aeruginosa biofilm formation by food waste materials.

The formation of bacterial biofilm on various surfaces has significant negative economic effects. The aim of this study was to find a simple procedure to decrease the Pseudomonas aeruginosa biofilm formation in a water environment by using different food waste biological materials as signal molecule adsorbents. The selected biomaterials did not reduce the cell growth but affected biofilm formation. Promising biomaterials were magnetically modified in order to simplify manipulation and facilitate their magnetic separation. The best biocomposite, magnetically modified spent grain, exhibited substantial adsorption of signal molecules and decreased the biofilm formation. These results suggest that selected food waste materials and their magnetically responsive derivatives could be applied to solve biofilm problems in water environment.

Induction of microglial toll-like receptor 4 by prothrombin kringle-2: a potential pathogenic mechanism in Parkinson's disease.

Microglia-mediated neuroinflammation may play an important role in the initiation and progression of dopaminergic (DA) neurodegeneration in Parkinson's disease (PD), and toll-like receptor 4 (TLR4) is essential for the activation of microglia in the adult brain. However, it is still unclear whether patients with PD exhibit an increase in TLR4 expression in the brain, and whether there is a correlation between the levels of prothrombin kringle-2 (pKr-2) and microglial TLR4. In the present study, we first observed that the levels of pKr-2 and microglial TLR4 were increased in the substantia nigra (SN) of patients with PD. In rat and mouse brains, intranigral injection of pKr-2, which is not directly toxic to neurons, led to the disruption of nigrostriatal DA projections. Moreover, microglial TLR4 was upregulated in the rat SN and in cultures of the BV-2 microglial cell line after pKr-2 treatment. In TLR4-deficient mice, pKr-2-induced microglial activation was suppressed compared with wild-type mice, resulting in attenuated neurotoxicity. Therefore, our results suggest that pKr-2 may be a pathogenic factor in PD, and that the inhibition of pKr-2-induced microglial TLR4 may be protective against degeneration of the nigrostriatal DA system in vivo.

Effective antifouling using quorum-quenching acylase stabilized in magnetically-separable mesoporous silica.

Highly effective antifouling was achieved by immobilizing and stabilizing an acylase, disrupting bacterial cell-to-cell communication, in the form of cross-linked enzymes in magnetically separable mesoporous silica. This so-called "quorum-quenching" acylase (AC) was adsorbed into spherical mesoporous silica (S-MPS) with magnetic nanoparticles (Mag-S-MPS), and further cross-linked for the preparation of nanoscale enzyme reactors of AC in Mag-S-MPS (NER-AC/Mag-S-MPS). NER-AC effectively stabilized the AC activity under rigorous shaking at 200 rpm for 1 month, while free and adsorbed AC lost more than 90% of their initial activities in the same condition within 1 and 10 days, respectively. When applied to the membrane filtration for advanced water treatment, NER-AC efficiently alleviated the biofilm maturation of Pseudomonas aeruginosa PAO1 on the membrane surface, thereby enhancing the filtration performance by preventing membrane fouling. Highly stable and magnetically separable NER-AC, as an effective and sustainable antifouling material, has a great potential to be used in the membrane filtration for water reclamation.

Design of quorum quenching microbial vessel to enhance cell viability for biofouling control in membrane bioreactor.

Quorum quenching (QQ) with a microbial vessel has recently been reported as an economically feasible biofouling control platform in a membrane bioreactor (MBR) for wastewater treatment. In this study, a quorum quenching MBR with a ceramic microbial vessel (CMV) was designed to overcome the extremely low F/M ratio inside a microbial vessel. The CMV was prepared with a monolithic ceramic microporous membrane and AHLdegrading QQ bacteria, Pseudomonas sp. 1A1. The "inner flow feeding mode" was introduced, under which fresh feed was supplied to the MBR only through the center lumen in the CMV. The inner flow feeding mode facilitated nutrient transport to QQ bacteria in the CMV and thus enabled relatively long-term maintenance of cell viability. The quorum quenching effect of the CMV on controlling membrane biofouling in the MBR was more pronounced with the inner flow feeding mode, which was identified by the slower increase in the transmembrane pressure as well as by the visual observation of a biocake that formed on the used membrane surface. In the QQ MBR with the CMV, the concentrations of extracellular polymeric substances were substantially decreased in the biocake on the membrane surface compared with those in the conventional MBR. The CMV also showed its potential with effective biofouling control over long-term operation of the QQ MBR.

Biofouling inhibition in MBR by Rhodococcus sp. BH4 isolated from real MBR plant.

It has been reported that an indigenous quorum quenching bacterium, Rhodococcus sp. BH4, which was isolated from a real plant of membrane bioreactor (MBR) has promising potential to control biofouling in MBR. However, little is known about quorum quenching mechanisms by the strain BH4. In this study, various characteristics of strain BH4 were investigated to elucidate its behavior in more detail in the mixed liquor of MBR. The N-acyl homoserine lactone hydrolase (AHL-lactonase) gene of strain BH4 showed a high degree of identity to qsdA in Rhodococcus erythropolis W2. The LC-ESI-MS analysis of the degradation product by strain BH4 confirmed that it inactivated AHL activity by hydrolyzing the lactone bond of AHL. It degraded a wide range of N-acyl homoserine lactones (AHLs), but there was a large difference in the degradation rate of each AHL compared to other reported AHL-lactonase-producing strains belonging to Rhodococcus genus. Its quorum quenching activity was confirmed not only in the Luria-Bertani medium, but also in the synthetic wastewater. Furthermore, the amount of strain BH4 encapsulated in the vessel as well as the material of the vessel substantially affected the quorum quenching activity of strain BH4, which provides useful information, particularly for the biofouling control in a real MBR plant from an engineering point of view.

Microbial population dynamics and proteomics in membrane bioreactors with enzymatic quorum quenching.

Quorum sensing gives rise to biofilm formation on the membrane surface, which in turn causes a loss of water permeability in membrane bioreactors (MBRs) for wastewater treatment. Enzymatic quorum quenching was reported to successfully inhibit the formation of biofilm in MBRs through the decomposition of signal molecules, N-acyl homoserine lactones (AHLs). The aim of this study was to elucidate the mechanisms of quorum quenching in more detail in terms of microbial population dynamics and proteomics. Microbial communities in MBRs with and without a quorum quenching enzyme (acylase) were analyzed using pyrosequencing and compared with each other. In the quorum quenching MBR, the rate of transmembrane pressure (TMP) rise-up was delayed substantially, and the proportion of quorum sensing bacteria with AHL-like autoinducers (such as Enterobacter, Pseudomonas, and Acinetobacter) also decreased in the entire microbial community of mature biofilm in comparison to that in the control MBR. These factors were attributed to the lower production of extracellular polymeric substances (EPS), which are known to play a key role in the formation of biofilm. Proteomic analysis using the Enterobacter cancerogenus strain ATCC 35316 demonstrates the possible depression of protein expression related to microbial attachments to solid surfaces (outer membrane protein, flagellin) and the agglomeration of microorganisms (ATP synthase beta subunit) with the enzymatic quorum quenching. It has been argued that changes in the microbial population, EPS and proteins via enzymatic quorum quenching could inhibit the formation of biofilm, resulting in less biofouling in the quorum quenching MBR.

Biofouling control with bead-entrapped quorum quenching bacteria in membrane bioreactors: physical and biological effects.

Recently, interspecies quorum quenching by bacterial cells encapsulated in a vessel was described and shown to be efficient and economically feasible for biofouling control in membrane bioreactors (MBRs). In this study, free-moving beads entrapped with quorum quenching bacteria were applied to the inhibition of biofouling in a MBR. Cell entrapping beads (CEBs) with a porous microstructure were prepared by entrapping quorum quenching bacteria ( Rhodococcus sp. BH4) into alginate beads. In MBRs provided with CEBs, the time to reach a transmembrane pressure (TMP) of 70 kPa was 10 times longer than without CEBs. The mitigation of biofouling was attributed to both physical (friction) and biological (quorum quenching) effects of CEBs, the latter being much more important. Because of the quorum quenching effect of CEBs, microbial cells in the biofilm generated fewer extracellular polymeric substances and thus formed a loosely bound biofilm, which enabled it to slough off from the membrane surface more easily. Furthermore, collisions between the moving CEBs and membranes gave rise to frictional forces that facilitated detachment of the biofilm from the membrane surface. CEBs bring bacterial quorum quenching closer to being a practical solution to the problem of biofouling in MBRs.

Control of membrane biofouling in MBR for wastewater treatment by quorum quenching bacteria encapsulated in microporous membrane.

Recently, enzymatic quorum quenching has proven its potential as an innovative approach for biofouling control in the membrane bioreactor (MBR) for advanced wastewater treatment. However, practical issues on the cost and stability of enzymes are yet to be solved, which requires more effective quorum quenching methods. In this study, a novel quorum quenching strategy, interspecies quorum quenching by bacterial cell, was elaborated and proved to be efficient and economically feasible biofouling control in MBR. A recombinant Escherichia coli which producing N-acyl homoserine lactonase or quorum quenching Rhodococcus sp. isolated from a real MBR plant was encapsulated inside the lumen of microporous hollow fiber membrane, respectively. The porous membrane containing these functional bacteria (i.e., "microbial-vessel") was put into the submerged MBR to alleviate biofouling on the surface of filtration membrane. The effect of biofouling inhibition by the microbial-vessel was evaluated over 80 days of MBR operation. Successful control of biofouling in a laboratory scale MBR suggests that the biofouling control through the interspecies quorum quenching could be expanded to the plant scale of MBR and various environmental engineering systems with economic feasibility.