Regenerated Cellulose Membranes Research Articles

Evaluation of Ribavirin-Poloxamer Microparticles for Improved Intranasal Absorption.

Ribavirin is a water-soluble antiviral compound which, owing to its inability to cross the blood–brain barrier, has limited effectiveness in treating viruses affecting the central nervous system. Direct nose-to-brain delivery was investigated for ribavirin in combination with poloxamer 188, an excipient known to enhance the absorption of drug compounds administered intranasally. Composite solid microparticles suitable for intranasal insufflation were prepared by suspending fine crystals of ribavirin in a matrix of poloxamer 188, which were cryogenically milled and characterized to ensure that ribavirin remained stable throughout preparation. In vitro diffusion of ribavirin across a semi-permeable regenerated cellulose membrane showed comparable cumulative drug release after 180 min from both fine solid particles (<20 µm) and 1:1 ribavirin:poloxamer microparticles (d50 = 20 µm); however, the initial release from polymer microparticles was slower, owing to gel formation on the membrane surface. When solid ribavirin was directly deposited on excised olfactory mucosa, either as fine drug particles or 1:1 ribavirin:poloxamer microparticles, permeation was significantly increased from microparticles containing poloxamer 188, suggesting additional interactions between the polymer and olfactory mucosa. These data indicate that for highly water-soluble drugs such as ribavirin or drugs subject to efflux by the nasal mucosa, a formulation of poloxmer-containing microparticles can enhance permeability across the olfactory epithelium and may improve direct nose-to-brain transport.

Remote Performance Modulation of Ultrafiltration Membranes by Magnetically and Thermally Responsive Polymer Chains.

Ultrafiltration membranes, that respond to an external magnetic field and local temperature have been developed. Surface-initiated activator-generated electron transfer (AGET) atom transfer radical polymerization (ATRP) has been used to graft poly(N-isopropylacrylamide) (PNIPAm) from the surface of 300 kDa regenerated cellulose membranes. The polymerization initiator was selectively attached to the entire membrane surface, only the outer membrane surface or only the inner pore surface. A superparamagnetic nanoparticle was attached to the end of the polymer chain. The DI water flux as well as the flux and rejection of bovine serum albumin were investigated in the absence and presence of a 20 and 1000 Hz oscillating magnetic field. In an oscillating magnetic field, the tethered superparamagnetic nanoparticles can cause movement of the PNIPAm chains or induce heating. A 20 Hz magnetic field maximizes movement of the chains. A 1000 Hz magnetic field leads to greater induced heating. PNIPAm displays a lower critical solution temperature at 32 °C. Heating leads to collapse of the PNIPAm chains above their Lower Critical Solution Temperature (LCST). This work highlights the versatility of selectively grafting polymer chains containing a superparamagnetic nanoparticle from specific membrane locations. Depending on the frequency of the oscillating external magnetic field, membrane properties may be tuned.

Ultrafiltration Fractionation of Bovine Hemoglobin Hydrolysates: Prediction of Separation Performances for Optimal Enrichment in Antimicrobial Peptide.

Hydrolysis of bovine hemoglobin (bHb), the main constituent of bovine cruor by-product, releases a natural antimicrobial peptide (NKT) which could present a major interest for food safety. To enrich this, tangential ultrafiltration can be implemented, but ultrafiltration conditions are mainly empirically established. In this context, the application of a simulation method for predicting the NKT yield and enrichment was investigated. Ultrafiltration performances were studied for decolored bHb hydrolysates at different degrees of hydrolysis (DH; 3%, 5%, 10% and 18%) and colored hydrolysates (3% and 5% DH) with 1 and 3 kg·mol−1 regenerated cellulose membranes. The simulation method helped to identify the most promising hydrolysate (in terms of NKT enrichment, yield and productivity) as the 3% DH colored hydrolysate, and UF conditions (volumetric reduction factor of 5 and 3 with 1 and 3 kg·mol−1 membrane, respectively) for higher antimicrobial recovery. A maximal enrichment factor of about 29 and NKT purity of 70% in permeate were observed. The results showed that the antimicrobial activity was in relation with the process selectivity and NKT purity. Finally, this reliable method, applied for predicting the ultrafiltration performances to enrich peptides of interest, is part of a global approach to rationally valorize protein resources from various by-products.

Design and evaluation of pharmaceutical availability, stability and quality of modified viscosity eye drops with choline salicylate

These studies investigate the possibility of developing and using choline salicylate (CS) in ophthalmic therapy in the form of eye drops with increased viscosity. A 0.5% addition of hydroxypropyl methylcellulose (HPMC) was used as the viscosity increasing agent. The ability of CS to cross a hydrophilic membrane (regenerated cellulose membrane) was assessed by determining a rate constant consistent with zero order kinetics. In studies on a porcine cornea, the ability of CS to penetrate into the structure of the cornea was confirmed by determining the content of CS in the cornea after 5 minutes and 3 hours exposure to eye drops. The quality parameters of eye drops were assessed: pH, viscosity, osmolarity and microbiological purity. Stability tests were also performed on eye drops stored in unit minims packaging and in multi-dose bottle packaging. The following storage conditions were adopted: 40°C/75% RH, 25°C/60% RH, 2-8°C. The sensitivity of CS to light was also confirmed. The UV and HPLC-UV methods were used to assess the CS content, while the HPLC-UV and HPLC-MS/MS methods were used to assess the chromatographic purity.

Modification of Electrospun Regenerate Cellulose Nanofiber Membrane via Atom Transfer Radical Polymerization (ATRP) Approach as Advanced Carrier for Laccase Immobilization.

This study aimed to modify an electrospun regenerated cellulose (RC) nanofiber membrane by surface grafting 2-(dimethylamino) ethyl methacrylate (DMAEMA) as a monomer via atom transfer radical polymerization (ATRP), as well as investigate the effects of ATRP conditions (i.e., initiation and polymerization) on enzyme immobilization. Various characterizations including XPS, FTIR spectra, and SEM images of nanofiber membranes before and after monomer grafting verified that poly (DMAEMA) chains/brushes were successfully grafted onto the RC nanofiber membrane. The effect of different ATRP conditions on laccase immobilization was investigated, and the results indicated that the optimal initiation and monomer grafting times were 1 and 2 h, respectively. The highest immobilization amount was obtained from the RC-Br-1h-poly (DMAEMA)-2h membrane (95.04 ± 4.35 mg), which increased by approximately 3.3 times compared to the initial RC membrane (28.57 ± 3.95 mg). All the results suggested that the optimization of initiation and polymerization conditions is a key factor that affects the enzyme immobilization amount, and the surface modification of the RC membrane by ATRP is a promising approach to develop an advanced enzyme carrier with a high enzyme loading capacity.

Fabrication and characterization of modified microcrystalline cellulose membrane as proton exchange membrane for direct methanol fuel cell

In this study, we report fabrication, and characterization of biopolymer-based membrane composite using microcrystalline cellulose (MCC) modified with phosphotungstic acid (PTA) and imidazole. The cellulose membrane was prepared by phase inversion method. The physicochemical properties of composite membranes were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and Electrochemical impedance spectroscopy (EIS). The regenerated cellulose membrane water uptake ability, and methanol uptake, derived from absorption of aqueous electrolytic solutions, also evaluated in this study to assess the successful applicability of the proposed membranes as PEM electrolytes for direct methanol fuel cell devices. XRD analysis shown that modification of the regenerated cellulose membrane had no effect on phase on cellulose membrane and cellulose membrane still retain the cellulose II crystalline structure which also confirmed with IR spectra of modified membrane which glycosidic and CH2 vibration peak around 900 and 1420 cm−1 that indicate intramolecular hydrogen bond did not alter after addition of dopant. Results indicate that modification of MCC with acid and base dopant could improve water management of regenerated membrane while also lessen methanol permeability inside membrane. Thus, modified regenerated cellulose membrane has high potential as alternative proton exchange membrane for direct methanol fuel cell.

Introduction and clearance of beta-glucan in the downstream processing of monoclonal antibodies.

β‐Glucan process‐related impurities can be introduced into biopharmaceutical products via upstream or downstream processing or via excipients. This study obtained a comprehensive process‐mapping dataset for five monoclonal antibodies to assess β‐glucan introduction and clearance during development and production runs at various scales. Overall, 198 data points were available for analysis. The greatest β‐glucan concentrations were found in the depth‐filtration filtrate (37–2,745 pg/ml). Load volume correlated with β‐glucan concentration in the filtrate, whereas flush volume was of secondary importance. Cation‐exchange chromatography significantly cleared β‐glucans. Furthermore, β‐glucan leaching from the Planova 20N virus removal filter was reduced by increasing the flush volume (1 vs. 10 L/m2). β‐glucan concentrations after filter flush with 10 L/m2 were consistently <10 pg/ml. No or only limited β‐glucan clearance was attained via ultrafiltration/diafiltration (UF/DF). However, during the first run with monoclonal antibody (mAb) 4, β‐glucan concentration in the UF/DF retentate was 10.8 pg/mg, potentially due to β‐glucan leaching from the first run with a regenerated cellulose membrane. Overall, β‐glucan levels in the final mAb drug substance were 1–12 pg/mg. Assuming high doses of 1,000–5,000 mg, a β‐glucan contamination at 20 pg/mg would translate to 20–100 ng/dose, which is below the previously suggested threshold for product safety (≤500 ng/dose).

Multilevel/hierarchical nanocomposite-imprinted regenerated cellulose membranes for high-efficiency separation: a selective recognition method with Au/PDA-loaded surface

Au/PDA-based multilevel nanocomposite imprinted membranes with high rebinding capacity and permselectivity performance were first proposed and developed for the selective recognition and separation of propranolol.

Nanomaterials fusing with the skin: Alpha-tocopherol phosphate delivery into the viable epidermis to protect against ultraviolet radiation damage

Vitamin E (alpha tocopherol, α-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating α-tocopherol (α-TP) to form a provitamin, improved its interactions with skin, its passage into the tissue, and thus its ability to protect the skin from ultraviolet radiation (UVR) damage. At pH 7.4, when the α-TPO4−1 microspecies predominated in solution, dynamic light scattering measurements showed that α-TP formed nanoaggregates with a median hydrodynamic diameter of 9 nm (Critical aggregation constant, CAC, – 4.2 mM). At 9.0 when the α-TPO4−2 microspecies predominated there was no aggregation. The passage of α-TP nanoaggregates through regenerated cellulose membranes was significantly slower than the α-TP monomers (at pH 9) suggesting that aggregation slowed diffusion. However, a lotion formulation containing the nanoaggregates delivered more α-TP into the skin compared to the formulation containing the monomers. In addition, the nanosized α-TP aggregates delivered 8-fold more active into the stratum corneum (SC) (252.2 μg/cm2 vs 29.5 μg/cm2) and 4 fold more active into the epidermis (85.1 μg/cm2 vs 19 μg/cm2, respectively, p < 0.05) compared to α-T. Langmuir subphase injection studies at pH 7.4 (surface pressure 10 mN m−1) showed that the α-TP nanoaggregates more readily fused with the SC compared to the monomers and the membrane compression studies demonstrated that α-TP fluidised the SC lipids. Together the fusion with the SC and its fluidisation were proposed as the causes of the better α-TP penetration into the skin, which enhanced potential of α-TP to protect from UVR-induced skin damage compared to α-T.

Melittin recovery with efficient phospholipase A2 removal of apitoxin from cross‐flow ultrafiltration process

AbstractBACKGROUNDBee venom (apitoxin) is a complex mixture of enzymes, peptides, amines, and other chemicals that presents diverse pharmaceutical activities. Melittin, a small peptide with 2.84 kDa, represents about 50% of this venom, on a dry basis. However, allergenic compounds, such as phospholipase A2 and hyaluronidase (enzymes with a molecular weight of 19 and 38 kDa, respectively), impair the direct use of apitoxin. The membrane separation process can be considered a potential approach for the fractionation of those components. Therefore, the cross‐flow ultrafiltration with a 10 kDa regenerated cellulose membrane was used to separate melittin from apitoxin, leading to lower fouling in the membrane.RESULTSThe strategy was divided into two steps: a 22 factorial design was conducted to evaluate apitoxin concentration and transmembrane pressure, followed by the study of flux decline and fouling mechanisms using the modified Hermia model. The best experimental condition led to 70% of melittin recovery and 99% of rejection of phospholipase A2. Membrane cleaning depicted a recovery of around 92% of flux and reduced 94% of transport resistance. The fouling mechanism revealed three mechanisms acting together in the process.CONCLUSIONThe results show significant values regarding the recovery of melittin and the removal of phospholipase A2, indicating that the cross‐flow ultrafiltration of apitoxin is an attractive option for the isolation of melittin, which has a high market value. © 2020 Society of Chemical Industry (SCI)

Tunable Wettability of Biodegradable Multilayer Sandwich-Structured Electrospun Nanofibrous Membranes.

This research aims to develop multilayer sandwich-structured electrospun nanofiber (ENF) membranes using biodegradable polymers. Hydrophilic regenerated cellulose (RC) and hydrophobic poly (lactic acid) (PLA)-based novel multilayer sandwich-structures were created by electrospinning on various copper collectors, including copper foil and 30-mesh copper gauzes, to modify the surface roughness for tunable wettability. Different collectors yielded various sizes and morphologies of the fabricated ENFs with different levels of surface roughness. Bead-free thicker fibers were collected on foil collectors. The surface roughness of the fine fibers collected on mesh collectors contributed to an increase in hydrophobicity. An RC-based triple-layered structure showed a contact angle of 48.2°, which is comparable to the contact angle of the single-layer cellulosic fabrics (47.0°). The polar shift of RC membranes on the wetting envelope is indicative of the possibility of tuning the wetting behavior by creating multilayer structures. Wettability can be tuned by creating multilayer sandwich structures consisting of RC and PLA. This study provides an important insight into the manipulation of the wetting behavior of polymeric ENFs in multilayer structures for applications including chemical protective clothing.

Enzyme mimics based membrane reactor for di(2-ethylhexyl) phthalate degradation

Di(2-ethylhexyl) phthalate (DEHP), the most abundantly used plasticizer, was considered to be a hazardous chemical that was difficult to be degraded naturally. In this study, inspired by the “catalytic triad’’ in serine proteases, an enzyme mimic material was developed by combining the proteases’s active sites of serine, histidine and aspartate (S-H-D) with the self-assembling sequence of LKLKLKL and the aromatic group of fluorenylmethyloxycarbonyl (Fmoc). By mixing the monomer of peptides containing separate S, H and D residues with a ratio of 2:1:1, the enzyme mimics were found to co- assemble into nanofibers (Co-HSD) and showed the highest activity towards DEHP degradation because of the synergistic effects of active sites, orderly secondary structure and stable molecular conformation. To further improve ability and applicability, the high active mimetic enzyme was immobilized onto regenerated cellulose (RC) membranes for DEHP degradation in a continuous recycling mode. The RC membranes were first functionalized by the NaIO4 oxidation method to form aldehyde groups and then conjugated with the enzyme mimics via Schiff-base reaction. As a biocatalytic membrane, this membrane could not only effectively degrade DEHP, but also showed good stability, thus establishing a promising biomaterial for large scale biodegradation of DEHP in water decontamination and liquid food depollution.

Correlation between membrane surface properties, polymer nature and fouling in skim milk ultrafiltration

The fouling of the membranes in skim milk ultrafiltration with the nominal molecular weight cut-off (MWCO) of 100 kDa fabricated from different polymers (polysulfone (PSF), polysulfonamide (PSA), aromatic polyamide (PA), polyacrylonitrile (PAN), cellulose acetate (CA) and regenerated cellulose (RC)) was studied. The membrane structure and physical-chemical properties of the selective layer were analyzed using scanning electron microscopy (SEM), atomic force microscopy (AFM), water contact angle (θ, °) measurements, free surface energy measurements and bovine serum albumin (BSA) adsorption. Additionally, the flux of the skim milk at the constant product concentration, protein adsorption, resistance of the gel layer of the membranes were determined. It was found that according to the decrease in water contact angle of the membrane selective layers membranes can be arranged in the series as follows: PSF > PSA > PA > PAN > CA > RC. It was revealed that there was no direct correlation between the membrane hydrophilicity and the protein adsorption. It was noted, that the studied membranes featured significantly different hydraulic resistances of the protein gel-layer, which can be considered as a secondary dynamic membrane. Comparison of the parameters – water contact angle and polar component of the free surface energy of the membrane selective layer, and normalized dipole moment of the membrane polymers - with the adsorption values of the proteins during ultrafiltration proves that the protein adsorption to the membrane surface increases with an increase in hydrophobicity and polarity of the membrane. The high protein adsorption by the moderately hydrophilic PAN membrane is due to the contribution of the high normalized dipole moment of the polymer. In the case of the polar RC-100 membrane, the influence of the membrane polarity was shown to be counter-balanced by its high hydrophilicity. The study highlights the impact of the physical-chemical properties and structure of the membrane on the protein gel-layer and thus their importance in membrane fouling control in dairy applications.

A cellulose-based nanofiltration membrane with a stable three-layer structure for the treatment of drinking water

Nanofiltration membrane (NFM) is an effective and advanced semi-permeable membrane (pore size: 1 ~ 2 nm) for deep purification of drinking water due to their low operating pressure and high divalent salt ion rejection. In this work, a stable cellulose-based polyamide nanofiltration membrane (NF-PDA-RCM) with a unique three-layered structure was prepared for advanced treatment of drinking water, via the method of chemical bond connection followed by the interfacial polymerization strategy. The regenerated cellulose membrane (RCM), as the supporting layer of NFM, prepared by phase inversion method has good physical compatibility and abundant porous channels. Further, the flux of NFM can be controlled by adjusting the pore size of the RCM. Through Michael addition reaction, the supporting layer and the active layer of NF-PDA-RCM are connected by the covalent bonds, resulting in a great improvement in the stability of NF-PDA-RCM. The resultant NF-PDA-RCM has increased rejection rate of MgSO4 (enhanced about 9.3%) and water-flux (enhanced about 78.5%) compared with that of no polydopamine (PDA) modified NFM. The RCM are completely biodegradable, allowing the NF-PDA-RCM to be a promising candidate for treating drinking water.

Fractionation of hydrolysates from concentrated lecithin free egg yolk protein dispersions by ultrafiltration

A membrane process for the recovery of ≥ 90 % of the soluble peptides (with antioxidant activity) found in concentrated lecithin-free egg yolk hydrolysates (LFEYH) was established. Hydrolysis of concentrated free lecithin egg yolk protein dispersions (10 and 20 %) was conducted with Alcalase 2.4L, an endoprotease from Bacillus Licheniformis. The obtained hydrolysates were fractionated by ultrafiltration (UF), where the effect of the membrane material and molecular weight cut-off (MWCO) was studied. Two flat sheet regenerated cellulose membranes and three tubular ceramic membranes with different MWCOs (50, 10 and 5kDa) were tested. Different hydrodynamic operating conditions were established in all membranes to work under sustainable flux during UF. The 50kDa ceramic membrane was found to be the most efficient in terms of flux (78.45 and 47.84kgm−2h-1 for 10 and 20 % protein dispersions, respectively) and showed lower fouling. The use of diafiltration (DF), allowed recovering more than 90 % of soluble and heat-stable peptides, which also showed high antioxidant activity, from hydrolysates produced in both concentrated (10 and 20 %) egg yolk protein dispersions.

Multilevel mineral-coated imprinted nanocomposite membranes for template-dependent recognition and separation: A well-designed strategy with PDA/CaCO3-based loading structure

In spite of the intense efforts in selective separation field, the utilization and preparation of membrane-associated molecularly imprinted membranes with both enhanced rebinding capacities and high permselectivity performance still remain strong challenges. Herein, the bioinspired PDA-modified porous regenerated cellulose membrane (pRCMs) with mineral-coated multilevel structure was first proposed for the preparation of PDA/CaCO3-based imprinted nanocomposite membranes (PCIMs), m-cresol was chosen as the template molecule. Importantly, this bioinspired methodology was redeveloped and optimized to obtain abundant and uniformly distributed CaCO3 nanocomposite on the surfaces of PDA@pRCMs. The as-designed sandwich-like imprinting structure were then constructed on PDA/CaCO3-based surfaces by developing a simple sol-gel imprinting process. Attributing to the design of the uniform CaCO3/PDA@pRCMs surfaces, amount of m-cresol-imprinted sites and permeation selectivity could be both optimized, it was no surprise that more excellent rebinding capacity (97.4 mg g−1), fast adsorption kinetics and high permselectivity coefficients (more than 13) were successfully achieved. Importantly, the whole synthesis process was conducted without complicated procedures and polluting the environment. Finally, the experimental results mentioned above, together with the green synthesis processes strongly demonstrated that our synthesis methodology of PCIMs had great potential for applications in various fields of selective separation, chemical industry, environment, biological medicine and so on.

Cellulose Membrane Composited with ZIF‐8 for Selective Separation of Rhodamine B

AbstractA composite membrane was prepared by in‐situ synthesis of ZIF‐8 on cellulose matrix in alkali/urea system. SEM revealed that ZIF‐8 particles are uniformly dispersed and tightly wrapped around the regenerated cellulose membrane which features a three‐dimensional porous structure. XRD, XPS and IR demonstrated the successful synthesis of ZIF‐8 on cellulose. Dye filtration experiments revealed high rejection rate (96 %) and selectivity for rhodamine B. Moreover, the composite membrane exhibited good cycling behavior with the rejection rate staying over 84 % after five cycles. The finding in this work provides a strategy for the rational design and fabrication of composite materials of cellulose and MOFs with promising application for wastewater purification.

Surface modification of regenerated cellulose membrane based on thiolactone chemistry – A novel platform for mixed mode membrane adsorbers

Mixed-mode membrane chromatography (MMC) is an effcient separation technology for protein purification. However, tedious preparation methods and difficulty on ligand density control for its stationary phase limit the application of MMC. Herein we explored a one-pot multistep reaction based on the thiolactone chemistry as a platform for membrane surface modification design toward mixed mode membrane adsorbers. The regenerated cellulose (RC) membrane was modified by the atom transfer radical polymerization (ATRP) of styrene-thiolactone (St-Tla), followed by the amine-thiol-ene conjugation. N-butylamine/methacrylic acid and octylamine/methacrylic acid were selected as the modifier to prepare two different mixed mode membrane adsorbers, RC-HIC/IEC (hydrophobic/ion-exchange) and RC-RPC/IEC (reversed phase/ion-exchange). SEM, FT-IR and XPS results showed that the membrane adsorbers were successfully prepared. The RC-HIC/IEC membrane had a statistic adsorption capacity of 73.5 µg/cm2 for human immunoglobulin G (IgG) under the conditions of pH = 8 and 0.5 mol/L NaCl in PB buffer. The RC-RPC/IEC membrane showed a capacity of 70 µg/cm2 for α-chymotrypsin (α-CTP) under the conditions of pH = 6.5 in PB buffer. The feasibility of tethering multi functions onto membrane surface via the thiolactone chemistry was demonstrated in this work.

Concentration and Purification of CollagenProteins by Ultrafiltration

The objective of the present study was to evaluate the performance of the ultrafiltration process on the recovery of collagen solution constituents at laboratory scale, using a tangential flow filtration, with flat regenerated cellulose membrane (5000 Da). Also permeate flows were evaluated along with the physicochemical characteristics of the concentrates, the permeates and feed solutions. The regenerated cellulose membranes were morphological studied by electron microscopy and characterized by water solutions permeation at different pressures. Keywords: collagen, concentration, protein, purification, ultrafiltration

Regenerated Cellulose Membrane from Peanut Shell for Biodiesel Purification

Biodiesel purification by water washing has been proved to be an unattractive process from an economic and environmental point of view. In this work, we propose the use of regenerated cellulose membranes from peanut shell as an alternative in the biodiesel purification. The preparation of the membranes was optimized from a central composite design, resulting in dense and non-porous membranes. However, in contact with biodiesel, the membranes undergo expansion due to the retention of methanol, water, and glycerol molecules, allowing the permeation of fatty acid methyl esters. The filtered biodiesel presents quality parameters, such as total ester content of 98.3 ± 1.4% and free glycerol content < 0.02%, in agreement with the main regulatory agencies. The regenerated cellulose membranes from peanut shell are easily prepared, with high repeatability (relative standard deviation (RSD) < 1.8%) and are presented as an economical and environmental solution for the biodiesel purification.