A high-performance polyacid ion exchange (IEX) nanofiber membrane was used in membrane chromatography for the recovery of lysozyme from chicken egg white (CEW). The polyacid IEX nanofiber membrane (P-BrA) was prepared by the functionalization of polyacrylonitrile (PAN) nanofiber membrane with ethylene diamine (EDA) and bromoacetic acid (BrA). The adsorption performance of P-BrA was evaluated under various operating conditions using Pall filter holder. The results showed that optimal conditions of IEX membrane chromatography for lysozyme adsorption were 10% (w/v) of CEW, pH 9 and 0.1 mL/min. The purification factor and yield of lysozyme were 402 and 91%, respectively. The adsorption process was further scaled up to a larger loading volume, and the purification performance was found to be consistent. Furthermore, the regeneration of IEX nanofiber membrane was achieved under mild conditions. The adsorption process was repeated for five times and the adsorption capacity of adsorber was found to be unaffected.
A single ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes inflammation of the colonic mucosa at the distal colon and rectum. The mainstay therapy involves anti-inflammatory immunosuppression based on the disease location and severity. The disadvantages of using systemic corticosteroids for UC treatment is the amplified risk of malignancies and infections. Therefore, topical treatments are safer as they have fewer systemic side effects due to less systemic exposure. In this context, pH sensitive and enzymatically triggered hydrogel of pectin (PC) and polyacrylamide (PAM) has been developed to facilitate colon-targeted delivery of budesonide (BUD) for the treatment of UC. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), swelling ratio, and drug release. FT-IR spectroscopy confirmed the grafting as well loading of BUD in hydrogel. XRD showed the amorphous nature of hydrogel and increment in crystallinity after drug loading. On the other hand, SEM showed that the hydrogels exhibited a highly porous morphology, which is suitable for drug loading and also demonstrated a pH-responsive swelling behaviour, with decreased swelling in acidic media. The in-vitro release of BUD from the hydrogel exhibited a sustained release behaviour with non-ficken diffusion mechanism. The model that fitted best for BUD released was the Higuchi kinetic model. It was concluded that enzyme/pH dual-sensitive hydrogels are an effective colon-targeted delivery system for UC.
A weak ion-exchange membrane (P-COOH) was synthesized by alkaline hydrolysis of a polyacrylonitrile nanofiber membrane prepared by electrospinning process. The P-COOH membrane was characterized for its physical properties and its application for purification of lysozyme from chicken egg white was investigated. The lysozyme adsorption efficiency of the P-COOH membrane operating in a stirred cell contactor (Millipore, Model 8010) was evaluated. The effects of key parameters such as the feed concentration, the rotating speed, the flow rate of feed and the operating pressure were studied. The results showed successful purification of lysozyme with a high recovery yield of 98% and a purification factor of 63 in a single step. The purification strategy was scaled-up to the higher feedstock loading volume of 32.7 and 70 mL using stirred cell contactors of Model 8050 and 8200, respectively. The scale-up processes achieved similar purification results, proving linear scalability of the purification technique adopted.
The research work was intended to formulate teriflunomide (TFM) loaded nano lipid-based (TNLC) carbopol-gellan gum in situ gel (TNLCGHG) and to investigate its therapeutic efficacy against glioma, a brain and spine tumor. Nanoformulation was developed using gellan gum and carbopol 974P as gelling and mucoadhesive agents, respectively, Glyceryl di-behenate and Glyceryl mono-linoleate blend as lipids, and Gelucire 44/14: water blend as surfactant system. Globule size, PDI, zeta potential, encapsulation efficiency, mucoadhesive strength, and nasal permeation were found to be 117.80 nm, 0.56, -21.86 mV, 81.16%, 4.80 g, and 904 μg/cm2, respectively. Anticancer efficacy of TFM-loaded nano lipid-based carbopol-gellan gum in situ gel (TNLCGHG) was determined in human U-87MG glioma cell line. IC50 was found 7.0 μg/mL for TNLCGHG, 4.8 μg/mL for pure TFM, and 78.5 μg/mL for TNLC, which approve the superiority of surfactant along with gellan gum as permeation enhancer. Brain Cmax for technetium (99mTC) labeled intranasal (i.n.) 99mTC-TNLCGHG was found 2-folds higher than 99mTC-TNLC (i.n.) and 99mTC-TNLC intravenous (i.v.) because the TNLCGHG formulation contains surfactant with natural gelling polymers, which promisingly improved drug permeability. Finally, this research revealed encouraging outcomes and successfully developed intranasal TNLCGHG nanoformulation as a novel tool for safe delivery of TFM in glioma patients.
Electrospinning technology was applied for the preparation of polyacrylonitrile (PAN) nanofiber membrane in this work. After hot pressing, alkaline hydrolysis and neutralization treatment, a weak acid cation exchange membrane (P-COOH) was prepared. By the covalent coupling reaction between the acidic membrane and aminomethane sulfonic acid (AMSA), a strong acidic nanofiber membrane (P-SO3H) was obtained. The surface morphology, chemical structure, and thermal stability of the prepared ion exchange membranes were analyzed via SEM, FTIR and TGA. Analytical results showed that the membranes were prepared successfully and thermally stable. The ion exchange membrane (IEX) was conducted with the newly designed membrane reactor, and different operating conditions affecting the adsorption efficiency of Toluidine Blue dye (TBO) were investigated by dynamic flow process. The results showed that dynamic binding capacity (DBC) of weak and strong IEX membranes for TBO dye was ~170 mg/g in a dynamic flow process. Simultaneously, the ion exchange membranes were also used for purifying lysozyme from chicken egg white (CEW). Results illustrated that the recovery yield and purification factor of lysozyme were 93.43% and 29.23 times (P-COOH); 90.72% and 36.22 times (P-SO3H), respectively. It was revealed that two type ion exchange membranes were very suitable as an adsorber for use in dye waste treatment and lysozyme purification process. P-SO3H strong ion-exchange membrane was more effective either removal of TBO dye or purification of lysozyme. The ion exchange membranes not only effectively purified lysozyme from CEW solution, but also effectively removed dye from wastewater.
Heavy metal pollution, such as lead, can cause contamination of water resources and harm human life. Many techniques have been explored and utilized to overcome this problem, with adsorption technology being the most common strategies for water treatment. In this study, carbon nanofibers, polyacrylonitrile (PAN)/sago lignin (SL) carbon nanofibers (PAN/SL CNF) and PAN/SL activated carbon nanofibers (PAN/SL ACNF), with a diameter approximately 300 nm, were produced by electrospinning blends of polyacrylonitrile and sago lignin followed by thermal and acid treatments and used as adsorbents for the removal of Pb(II) ions from aqueous solutions. The incorporation of biodegradable and renewable SL in PAN/SL blends fibers produces the CNF with a smaller diameter than PAN only but preserves the structure of CNF. The adsorption of Pb(II) ions on PAN/SL ACNF was three times higher than that of PAN/SL CNF. The enhanced removal was due to the nitric acid treatment that resulted in the formation of surface oxygenated functional groups that promoted the Pb(II) ions adsorption. The best-suited adsorption conditions that gave the highest percentage removal of 67%, with an adsorption capacity of 524 mg/g, were 40 mg of adsorbent dosage, 125 ppm of Pb(II) solution, pH 5, and a contact time of 240 min. The adsorption data fitted the Langmuir isotherm and the pseudo-second-order kinetic models, indicating that the adsorption is a monolayer, and is governed by the availability of the adsorption sites. With the adsorption capacity of 588 mg/g, determined via the Langmuir isotherm model, the study demonstrated the potential of PAN/SL ACNFs as the adsorbent for the removal of Pb(II) ions from aqueous solution.
Nanofiber membrane chromatography integrates liquid membrane chromatography and nanofiber filtration into a single-step purification process. Nanofiber membrane can be functionalised with affinity ligands for promoting binding specificity of membrane. Dye molecules are a good affinity ligand for nanofiber membrane due to their low cost and high binding affinity. In this study, a dye-affinity nanofiber membrane (P-Chitosan-Dye membrane) was prepared by using polyacrylonitrile nanofiber membrane modified with chitosan molecules and immobilized with dye molecules. Reactive Orange 4, commercially known as Procion Orange MX2R, was found to be the best dye ligand for membrane chromatography. The binding capacity of P-Chitosan-Dye membrane for lysozyme was investigated under different operating conditions in batch mode. Furthermore, desorption of lysozyme using the P-Chitosan-Dye membrane was evaluated systematically. The recovery percentage of lysozyme was found to be ~100%. The optimal conditions obtained from batch-mode study were adopted to develop a purification process to separate lysozyme from chicken egg white. The process was operated continuously using the membrane chromatography and the characteristic of the breakthrough curve was evaluated. At a lower flow rate (i.e., 0.1 mL/min), the total recovery of lysozyme and purification factor of lysozyme were 98.59% and 56.89 folds, respectively.
An optical genosensor based on Schiff base complex (Zn2+ salphen) DNA label and acrylic microspheres (AMs) as polymer support of the capturing DNA probe (cpDNA) was developed for dengue virus serotype 2 (DEN-2) detection via reflectance spectrophotometric method. The solid-state optical DNA biosensor showed high selectivity and specificity up to one-base mismatch in the target DNA sequence owing to the salphen chemical structure that is rich in localized electrons, and allowed π-π stacking interaction between stacked base pairs of double-stranded DNA (dsDNA). The reflectometric DNA microsensor demonstrated a broad linear detection range towards DEN-2 DNA from 1 × 10-15 M to 1 × 10-3 M with a low limit of detection (LOD) obtained at 1.21 × 10-16 M. The DNA biosensor gave reproducible optical response with a satisfactory relative standard deviation (RSD) at 3.1%, (n = 3), and the reflectance response was stable even after four regeneration cycles of the DNA biosensor. The optical genosensor was proven comparable with standard reverse transcription polymerase chain reaction (RT-PCR) in detecting DEN-2 genome acquired from clinical samples of serum, urine and saliva of dengue virus infected patients under informed consent. The developed reflectometric DNA biosensor is advantageous in offering an early DEN-2 diagnosis, when fever symptom started to manifest in patient.
Vaccine administration via the oral route is preferable to parenteral routes due to ease of administration. To date, most available oral vaccines comprises of live attenuated pathogens as oppose to peptide-based vaccines due to its low bioavailability within the gastrointestinal (GI) tract. Over the years, probiotic-based peptide delivery vehicles comprising of lactic acid bacteria such as Lactococcus lactis has emerged as an interesting alternative due to its generally recognized as safe (GRAS) status, a fully sequenced genome, transient gut colonization time, and is an efficient cellular factory for heterologous protein production. However, its survivability through the GI tract is low, thus better delivery approaches are being explored to improve its bioavailability. In this study, we employ the incorporation of a double coated mucoadhesive film consisting of sodium alginate and Lycoat RS 720 film as the inner coat. The formulated film exhibits good mechanical properties of tensile strength and percent elongation for manipulation and handling with an entrapment yield of 93.14±2.74%. The formulated mucoadhesive film is subsequently loaded into gelatin capsules with an outer enteric Eudragit L100-55 coating capable of a pH-dependent breakdown above pH 5.5 to protect against gastric digestion. The final product and unprotected controls were subjected to in vitro simulated gastrointestinal digestions to assess its survivability. The product demonstrated enhanced protection with an increase of 69.22±0.67% (gastric) and 40.61±8.23% (intestinal) survivability compared to unprotected controls after 6 hours of sequential digestion. This translates to a 3.5 fold increase in overall survivability. Owing to this, the proposed oral delivery system has shown promising potential as a live gastrointestinal vaccine delivery host. Further studies involving in vivo gastrointestinal survivability and mice immunization tests are currently being carried out to assess the efficacy of this novel oral delivery system in comparison to parenteral routes.
Purpose: This study aimed to evaluate the effects of various computed tomography (CT) acquisition parameters and metal artifacts on CT number measurement for CT thermometry during CT-guided thermal ablation. Methods: The effects of tube voltage (100-140 kVp), tube current (20-250 mAs), pitch (0.6-1.5) and gantry rotation time (0.5, 1.0 s) as well as metal artifacts from a radiofrequency ablation (RFA) needle on CT number were evaluated using liver tissue equivalent polyacrylamide (PAA) phantom. The correlation between CT number and temperature from 37 to 80 °C was studied on PAA phantom using optimum CT acquisition parameters. Results: No statistical significant difference (p > 0.05) was found on CT numbers under the variation of different acquisition parameters for the same temperature setting. On the other hand, the RFA needle has induced metal artifacts on the CT images of up to 8 mm. The CT numbers decreased linearly when the phantom temperature increased from 37 to 80 °C. A linear regression analysis on the CT numbers and temperature suggested that the CT thermal sensitivity was -0.521 ± 0.061 HU/°C (R2 = 0.998). Conclusion: CT thermometry is feasible for temperature assessment during RFA with the current CT technology, which produced a high CT number reproducibility and stable measurement at different CT acquisition parameters. Despite being affected by metal artifacts, the CT-based thermometry could be further developed as a tissue temperature monitoring tool during CT-guided thermal ablation.
Novel pH sensitive N-succinyl chitosan-g-poly (acrylic acid) hydrogels were synthesized through free radical mechanism. Rheometer was used to observe the mechanical strength of the hydrogels. In vitro degradation was conducted in SIF (pH 7.4). The effect of concentration of monomers, initiator, and crosslinking agent and pH and ionic strength of NaCl, CaCl2, and AlCl3 on swelling of the hydrogels was observed. The results showed that equilibrium swelling ratio was highly influenced by concentration of monomers, initiator, and crosslinking agent concentration, and pH and salt solutions of NaCl, CaCl2, and AlCl3. The swelling kinetics revealed that swelling followed non-Fickian anomalous transport. Furthermore, theophylline loading (DL %) and encapsulation efficiency (EE %) of the hydrogels was in the range of 15.5 ± 0.15-22.8 ± 0.06% and 62 ± 0.15-91 ± 0.26%, respectively. The release of theophylline in physiological mediums was strongly influenced by the pH. The theophylline release was in the range of 51 ± 0.20-92 ± 0.12% in SIF and 7.4 ± 0.02-14.9 ± 0.03% in SGF (pH 1.2), respectively. The release data fitted well to Korsmeyer-Peppas model. The chemical activity of the theophylline suggested that drug maintained its chemical activity after release in vitro. The results suggest that synthesized hydrogels are excellent drug carriers.
This research aims to compare the ability of smart hydrogel in removing the methylene blue prepared by using two different radiation methods. The extracted pectin from the dragon fruit peel (Hylocereus polyrhizus) was used with acrylic acid (AA) to produce a polymerized hydrogel through gamma and microwave radiation. The optimum hydrogel swelling capacity was obtained by varying the dose of radiation, pectin to AA ratio and pH used. From the array of samples, the ideal hydrogel was obtained at pH 8 with a ratio of 2:3 (pectin: AA) using 10 kGy and 400 W radiated gamma and microwave respectively. The performance of both hydrogels namely as Pc/AA(G) (gamma) and Pc/AA(Mw) (microwave) were investigated using methylene blue (MB) adsorption studies. In this study, three variables were manipulated, pH and MB concentration and hydrogel mass in order to find the optimum condition for the adsorption. Results showed that 20 mg of Pc/AA(G) performed the highest MB removal which was about 45% of 20 mg/L MB at pH 8. While 30 mg of Pc/AA(Mw) able to remove up to 35% of 20 mg/L MB at the same pH condition. To describe the adsorption mechanism, both kinetic models pseudo-first-order, pseudo-second-order were employed. The results from kinetic data showed that it fitted the pseudo-first-order as compared to pseudo-second-order model equation. This study provides alternative of green, facile and affective biomaterial for dye absorbents that readily available.
In this study, chitosan-poly(methacrylic acid-co-N-isopropylacrylamide) [chitosan-p(MAA-co-NIPAM)] hydrogels were synthesized by emulsion polymerization. In order to be used as a carrier for drug delivery systems, the hydrogels had to be biocompatible, biodegradable and multi-responsive. The polymerization was performed by copolymerize MAA and NIPAM with chitosan polymer to produce a chitosan-based hydrogel. Due to instability during synthesis and complexity of components to produce the hydrogel, further study at different times of reaction is important to observe the synthesis process, the effect of end product on swelling behaviour and the most important is to find the best way to control the hydrogel synthesis in order to have an optimal swelling behaviour for drug release application. Studied by using Fourier transform infra-red (FTIR) spectroscopy found that, the synthesized was successfully produced stable chitosan-based hydrogel with PNIPAM continuously covered the outer surface of hydrogel which influenced much on the stability during synthesis. The chitosan and PMAA increased the zeta potential of the hydrogel and the chitosan capable to control shrinkage above human body temperature. The chitosan-p(MAA-co-NIPAM) hydrogels also responses to pH and temperature thus improved the ability to performance as a drug carrier.
Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
Commercial low-density polyethylene (LDPE) films were UV/ozone treated and coated using a layer-by-layer (LbL) technique by alternating the deposition of polyethyleneimine (PEI) and poly(acrylic acid) (PAA) polymer solutions and antimicrobial silver (Ag). The effects of the initial pH of the PEI/PAA polymer solutions alternating layers (pH 10.5/4 or 9/6.5) on the antimicrobial activity of the developed LbL coatings combined with Ag against Gram-negative and Gram-positive bacteria were investigated. The results from fourier transform infrared spectroscopy and toluidine blue O assay showed that LDPE LbL coated using PEI/PAA polymer solutions with initial pH of 10.5/4 significantly increased the presence of carboxylic acid groups and after Ag attachment the coating had higher antimicrobial activity against both Gram-negative and Gram-positive bacteria compared to the LDPE LbL coated using PEI/PAA polymer solutions with initial pH of 9/6.5. The LDPE LbL coated films using non-modified pH PEI/PAA polymer solutions decreased the water contact-angle indicating an increased hydrophilicity of the film, also increased the tensile strength and roughness of LDPE LbL coated films compared to uncoated LbL samples. The LDPE LbL coated films attached with Ag(+) were UV/ozone treated for 20 min to oxidise Ag(+) to Ag(0). The presence of Ag(0) (Ag nanoparticles (NPs)) on the LDPE LbL coated films was confirmed by XRD, UV-vis spectrophotometer and colour changes. The overall results demonstrated that the LbL technique has the potential to be used as a coating method containing antimicrobial Ag NPs and that the manufactured films could potentially be applied as antimicrobial packaging.
The purpose of this work is to remove Pb(II) from the aqueous solution using a type of hydrogel composite. A hydrogel composite consisting of waste linear low density polyethylene, acrylic acid, starch, and organo-montmorillonite was prepared through emulsion polymerization method. Fourier transform infrared spectroscopy (FTIR), Solid carbon nuclear magnetic resonance spectroscopy (CNMR)), silicon(-29) nuclear magnetic resonance spectroscopy (Si NMR)), and X-ray diffraction spectroscope ((XRD) were applied to characterize the hydrogel composite. The hydrogel composite was then employed as an adsorbent for the removal of Pb(II) from the aqueous solution. The Pb(II)-loaded hydrogel composite was characterized using Fourier transform infrared spectroscopy (FTIR)), scanning electron microscopy (SEM)), and X-ray photoelectron spectroscopy ((XPS)). From XPS results, it was found that the carboxyl and hydroxyl groups of the hydrogel composite participated in the removal of Pb(II). Kinetic studies indicated that the adsorption of Pb(II) followed the pseudo-second-order equation. It was also found that the Langmuir model described the adsorption isotherm better than the Freundlich isotherm. The maximum removal capacity of the hydrogel composite for Pb(II) ions was 430mg/g. Thus, the waste linear low-density polyethylene-g-poly (acrylic acid)-co-starch/organo-montmorillonite hydrogel composite could be a promising Pb(II) adsorbent.
Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.
Stimuli-responsive bacterial cellulose-g-poly(acrylic acid) hydrogels were investigated for their potential use as an oral delivery system for proteins. These hydrogels were synthesized using electron beam irradiation without any cross-linking agents, thereby eliminating any potential toxic effects associated with cross-linkers. Bovine serum albumin (BSA), a model protein drug, was loaded into the hydrogels, and the release profile in simulated gastrointestinal fluids was investigated. Cumulative release of less than 10% in simulated gastric fluid (SGF) demonstrated the potential of these hydrogels to protect BSA from the acidic environment of the stomach. Subsequent conformational stability analyses of released BSA by SDS-PAGE, circular dichroism, and an esterase activity assay indicated that the structural integrity and bioactivity of BSA was maintained and preserved by the hydrogels. Furthermore, an increase in BSA penetration across intestinal mucosa tissue was observed in an ex vivo penetration experiment. Our fabricated hydrogels exhibited excellent cytocompatibility and showed no sign of toxicity, indicating the safety of these hydrogels for in vivo applications.
Micro-emulsions and sometimes nano-emulsions are well known candidates to deliver drugs locally. However, the poor rheological properties are marginally affecting their acceptance pharmaceutically. This work aimed to modify the poor flow properties of a nano-scaled emulsion comprising palm olein esters as the oil phase and ibuprofen as the active ingredient for topical delivery. Three Carbopol ® resins: 934, 940 and Ultrez 10, were utilized in various concentrations to achieve these goals. Moreover, phosphate buffer and triethanolamine solutions pH 7.4 were used as neutralizing agents to assess their effects on the gel-forming and swelling properties of Carbopol ® 940. The addition of these polymers caused the produced nano-scaled emulsion to show a dramatic droplets enlargement of the dispersed globules, increased intrinsic viscosity, consistent zeta potential and transparent-to-opaque change in appearance. These changes were relatively influenced by the type and the concentration of the resin used. Carbopol ® 940 and triethanolamine appeared to be superior in achieving the proposed tasks compared to other materials. The higher the pH of triethanolamine solution, the stronger the flow-modifying properties of Carbopol ® 940. Transmission electron microscopy confirmed the formation of a well-arranged gel network of Carbopol ® 940, which was the major cause for all realized changes. Later in vitro permeation studies showed a significant decrease in the drug penetration, thus further modification using 10% w/w menthol or limonene as permeation promoters was performed. This resulted in in vitro and in vivo pharmacodynamics properties that are comparably higher than the reference chosen for this study.